Chimeric biosensor for the detection 2'3'-cyclic gmp-amp (CGAMP) and methods of use thereof

Abstract

This inventive technology includes systems, methods and compositions to detect 2'3'-cGAMP. In one preferred aspect, the invention is directed to one or more chimeric fusion peptides that are capable of coupling 2'3'-cGAMP analyte levels to an output, such as an enzymatic output.

Description

[0001] CHIMERIC BIOSENSOR FOR THE DETECTION 2’3’-CYCLIC GMP- AMP (cGAMP) AND METHODS OF USE THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This International PCT application claims the benefit of and priority to U.S. Provisional Application No. 63 / 447,555 filed February 22, 2023, the specification, claims and drawings of which are incorporated herein by reference in their entirety. STATEMENT OF GOVERNMENT INTEREST This invention was made with government support under grant number AT012346 awarded by the National Institutes of Health. The government retains certain rights in this invention. SEQUENCE LISTING The instant application contains contents of the electronic sequence listing (90245.00691- Sequence Listing.xml; Size: 14,762 bytes; and Date of Creation: February 22, 2024) is herein incorporated by reference in its entirety. TECHNICAL FIELD The inventive technology is directed to the field of biosensors, and in particular novel chimeric biosensor peptides configured to detect and quantifying 2’3’-Cyclic-GMP-AMP (2’3’ cGAMP). BACKGROUND The human cGAS-cGAMP-STING pathway links detection of DNA in the cytoplasm with a potent antimicrobial and anticancer immune response (Fig.3). When cGAS binds DNA localized outside the nucleus it synthesizes the nucleotide second messenger 2’3’-cGAMP, which diffuses throughout the cell.2’3’-cGAMP, also referred to herein as cGAMP, binds STING which activates a signaling cascade resulting in type I interferon activation, NF-κB-mediated inflammation, autophagy, and cell death. STING signaling was discovered in the context of infection, where this pathway links detection of pathogen DNA to antiviral and antibacterial signaling. However, the cGAS-cGAMP-STING pathway has recently gained attention for its pivotal role in anticancer signaling. Mice deficient in either cGAS or STING are unable to mount anticancer immune responses. In addition, the activity of some anticancer therapeutics, such as immune checkpoint inhibitors, are dependent on cGAS and STING. These findings spotlight the important role of cGAS-cGAMP-STING in disease. Cyclic dinucleotides, like 2’3’-cGAMP are enzymatically synthesized by joining two nucleotide triphosphates (in this case from ATP and GTP). The phosphodiester bonds linking the nucleotides can be either 3’–5’ linked such as in RNA and DNA, or 2’–5’ linked, a comparatively rare bond in biology.2’3’- cGAMP is asymmetric with one 2’ bond and one 3’ bond, giving the name 2’3’-cGAMP. Nucleotides are ideal second messengers because they are synthesized from abundant precursor NTPs and rapidly alter cellular signaling by binding specific receptors (e.g. STING). Given four abundant ribonucleotide triphosphates and different phosphodiester bonds, many cyclic dinucleotides are possible. Cyclic dinucleotides like 2’3’-cGAMP are also highly stable, which enables both intracellular signaling and uptake of these molecules from the extracellular space.2’3’-cGAMP was discovered in 2013 as the first and only cyclic dinucleotide in mammalian cells. Traditional methods for quantifying 2’3’-cGAMP are insufficient, and are a major obstacle to surveying biological and microbial samples (e.g. patient microbiomes or bacterial lysates). Mass spectrometry is the gold standard in the field, however, the limit of detection is very high because nucleotides notoriously do not ionize well without being destroyed and do not separate well using conventional reverse-phase chromatography. Published FRET-based sensors based on mouse STING have a lower limit of detection but cannot distinguish between 2’3’-cGAMP, 3’3’- cGAMP, and other more abundant bacterial nucleotides. Commercial kits for 2’3’-cGAMP detection are available, however are insufficient for detecting 2’3’ cGAMP in complex biological microbial samples and are expensive at scale. As such, there exists a long-felt need for a simple, inexpensive, and effective system to detect and quantify the presence and synthesis of 2’3’-cGAMP, in particular in complex biological samples, as well as diagnostics and therapeutics that are directed to the STING-pathway. SUMMARY OF THE INVENTION This inventive technology includes systems, methods and compositions to detect 2’3’- cGAMP. In one preferred aspect, the invention is directed to one or more chimeric fusion peptides that are capable of coupling soluble 2’3’-cGAMP analyte levels to an output, such as an enzymatic output. In one embodiment, a peptide binds to, and is activated by 2’3’-cGAMP. This binding peptide is fused with an output domain, which can include an enzymatic output such as a nuclease. In this preferred configuration, the chimeric fusion peptide of the invention forms a biosensor coupling 2’3’-cGAMP levels to nuclease activity. Naturally, as noted below, such endonuclease output signal is exemplary only as other detectable signals are contemplated within the scope of the invention. In one preferred aspect, the invention includes a novel biosensor configured to detect 2’3’-cGAMP through the signal input domain. The signal output domain of the 2’3’-cGAMP detection biosensor can be fused with a nuclease which may include DNase activity, which can be used to detect using fluorescent DNA probes or simple agarose gel electrophoresis. In another aspect the invention includes a biosensor for detecting 2’3’-cGAMP including a chimeric peptide having a 2′,3′-cGAMP signal input domain, and a signal output domain. The signal output domain of the biosensor can be activated through the binding of 2′,3′-cGAMP to the signal input domain, which can further be measured and correlated to a level of 2′,3′-cGAMP present in a sample. In one preferred aspect, the signal input domain and / or signal output domains of the invention can be derived from a SAVED family receptor domain, preferably from bacteria. In another preferred aspect, the signal input domain and / or signal output domains of the invention can be derived from a SAVED domain containing all or part of a protein encoded in an operon with a cGAS / DncV-like nucleotidyltransferase (CD-NTase). In one preferred aspect, the signal input domain and / or signal output domains of the invention can be derived from a CD-NTase enzyme that synthesizes 2’,3’-cGAMP. In one preferred aspect, a signal input domain of the invention includes a SAVED005-05 (SAVEDCb) domain from Clostridium botulinum. In an alternative preferred aspect, the signal input domain includes a peptide according to amino acid sequence SEQ ID NO.6, or a sequence having at least 90% sequence homology with SEQ ID NO.6. In another preferred aspect, the signal output domain of the biosensor includes a domain having a nuclease activity, protease activity, and / or oligomerization activity. In this preferred aspect, the signal output domain of the biosensor includes a nuclease domain activated through the binding of cGAMP to a signal input domain. The biosensor of the invention may include a signal output domain comprise a HNH12 domain from Geobacillus sp. (HNHGb). In another preferred aspect, the signal output domain includes a peptide according to amino acid sequence SEQ ID NO. 5, or a sequence having at least 90% sequence homology with SEQ ID NO.5. Additional aspects of the invention include a chimeric fusion peptide biosensor having one or more tags. In a preferred aspect, the tag of invention can comprise a tag to assist in the isolation and purification of the biosensor, and / or a tag that increases expression of the biosensor in a protein expression system, such as a bacterial expression system like E. Coli. Additional aspects of the inventive technology include methods of detecting 2’3’-cGAMP in a sample, and preferably a biological sample. In this preferred aspect, the method of detecting 2′,3′-cGAMP includes contacting a sample with the biosensor of the invention and measuring the activity of the signal output domain, which can be correlated with the level of the activity of a signal output domain with a level of cGAMP in the sample. Additional aspects of the inventive technology include a diagnostic device for detecting 2’3’-cGAMP in a sample, and preferably a biological sample. Additional aspect further includes a chimeric 2′,3′-cGAMP biosensor peptide c provided as part of a kit, containing a quantity of isolated biosensor in a container, and instructions for use. Additional aspects of the inventive technology will be evident from the detailed description and figures presented below. BRIEF DESCRIPTION OF THE FIGURES FIGS 1a-g: Construction of a 2’,3’-cGAMP biosensor using bacterial SAVED005 clade receptors. (a) Schematic indicating the domain architecture and amino acid boundaries for three proteins: a SAVED receptor from Geobacillus, a SAVED receptor from Clostridium botulinum, and a chimeric protein. The native SAVED from Geobacillus is a nuclease domain (HNH12) fused to a nucleotide sensing domain (SAVED-12). The native SAVED from Clostridium botulinum is a transmembrane domain (2TM) fused to a nucleotide sensing domain (SAVED005-05). The chimeric protein joins HNH12 with the SAVED005-05 domain, thereby incorporating the enzymatic output from Geobacillus with the nucleotide specificity of Clostridium botulinum. The resulting protein is called “Chimera 10” and now only activates nuclease activity in the presence of 2’,3’-cGAMP. (b) Microscale thermophoresis experiment of the native 2TM-SAVED005-03 protein from Bacillus thuringiensis, a protein similar to SAVED from Clostridium botulinum, confirming binding of 2’,3’-cGAMP at a Kd of ~ 15 nM. (c) Coomassie-stained SDS-PAGE gel indicating the expression and purification of 6xhis-SUMO- Chimera10 in E. coli BL21(DE3) cells. IMAC = immobilized metal affinity chromatography. The 6xhis-SUMO tag was removed from the final construct prior to activity assays. (d) DNA degradation assay / activity test of chimeric construct. Data is an agarose gel indicating nuclease activity of the native SAVED receptor from Geobacillus and chimera 10 on a linear DNA substrate in response to various cGAMP isoforms and other cyclic oligonucleotides. Chimera 10 only responds to 2’,3’-cGAMP. (e) Fluorescent DNase reporter assay (DNase-Alert) indicating activity of Chimera10 in response to various 2’,3’-cGAMP concentrations. Cleavage of the reporter substrate by nuclease results in higher fluorescent units (RFU = relative fluorescence units with excitation / emission at 535 / 565 nm). (f) Kinetic measurement of the same assay shown in (e). (g) A generic design strategy for chimeric effector-SAVED005 related receptors (005-05 is used as an example). The SAVED domain confers specificity or “signal input”. The effector domain confers the format of the “signal output” and could be a nuclease, protease, oligomerization, or other domain. FIG. 2: Expression vector schematic. Backbone: pETSUMO2, IPTG inducible, T7 Promoter. Cloning details: backbone cut with BamHI / NotI enzymes (from pAW1487 backbone), cloned fragment with BamHI / NotI sites and constructed using Gibson Assembly. FIG. 3. The human cGAScGAMP-STING pathway. Cyclic GMP–AMP Synthase (cGAS) binds double stranded DNA to synthesize 2’,3’-cyclic GMP–AMP (2’3’-cGAMP), activating Stimulator of Interferon Genes (STING). STING signaling is crucial for anticancer signaling. FIGS 4a-b. A genetic assay to identify candidate 2’3’-cGAMP activated receptors. (a) Nucleotide receptors are encoded in operons with cGAS-like enzymes and are highly specific to the nucleotide synthesized by their cGAS. (b) Receptors predicted to be nucleases were cloned into our genetic assay that measures receptor activation by quantifying cell death when human Cgas is expressed. Sensor activation reflects changes in colony forming units, and low-high activation represents a 4-log difference. Receptor nucleases are arbitrarily labeled. Three nucleases were activated by 2’3’-cGAMP. FIG a-b.2’3’-cGAMP-activated nucleases can be used as biosensors. (a) Schematic of how candidate 2’3’-cGAMP-activated nucleases couple nucleotide concentration to DNA destruction. (b) HNH12 was produced recombinantly and mixed with DNA + / - 2’3’-cGAMP or 3’3’-cGAMP at 0, 10, and 1000 nM. DNA integrity was visualized by agarose gel electrophoresis. FIG 6. Measuring 2’3’-cGAMP in cellular lysates. Chimera10 displays higher activity, reflecting a higher 2’3’-cGAMP concentration, in lysate derived from WT CdnB expressed during phage infection, as compared to a catalytically dead strain or an empty vector. DETAILED DESCRIPTION OF THE INVENTION The following detailed description is provided to aid those skilled in the art in practicing the various embodiments of the present disclosure, including all the methods, uses, compositions, etc., described herein. Even so, the following detailed description should not be construed to unduly limit the present disclosure, as modifications and variations in the embodiments herein discussed may be made by those of ordinary skill in the art without departing from the spirit or scope of the present discoveries. The present invention relates to systems, methods and compositions for the detection of target molecules, and on particular 2’3’-cGAMP. In one preferred embodiment, the inventive technology may include systems, methods and compositions for the detection of 2’3’-cGAMP in a biological sample using a biosensor peptide. Specifically, the present invention is direct to a highly sensitive, and specific 2’3’-cGAMP sensor. As shown in Figure 4, Applicants screened over 30 different receptor proteins for activation by 2’3’-cGAMP using a genetic assay for receptor activation (Fig. 4). These screens identified three different candidate sensors proteins. All of the candidates are both found in operons with cGAS-like enzymes from clade B, which was found to synthesize 2’3’-cGAMP. These data are consistent with the model that CBASS receptors are specific to nucleotides made by adjacent cGAS-like enzymes and clade B cGAS-like enzymes synthesize 2’3’-cGAMP. Again, referring to Figure 4, Receptor12 is activated by 2’3’-cGAMP but not the related isomer 3’3’-cGAMP, however the limit of nucleotide detection is 1 μM (Fig. 5). These findings demonstrated strong proof that the use of chimeric biosensor peptides enables construction of a sensitive 2’3’-cGAMP sensor protein. The chimeric biosensor peptide of the invention can include a signal output domain comprising all or part of a 2’3’-cGAMP receptor encoded in bacterial cGAS operons. Notably, many bacterial cGAS-like enzymes are encoded in antiphage signaling systems called CBASS, which use cGAS-like enzymes as phage sensors and receptor proteins to coordinate antiphage signaling. These receptor proteins are easy to identify, couple nucleotide concentration to enzymatic activity, and are highly-sensitive and specific for their cognate molecule (Fig. 4). A proportion of receptor proteins are nucleases that are activated by their cognate nucleotide. As shown below, these coupled characteristics can be modified so as to generate a novel heterologous chimeric biosensor peptide having a 2’3’-cGAMP activated nuclease. In a preferred embodiment, the 2’3’-cGAMP sensor of the invention includes a biosensor configured to detect and / or quantify 2′,3′-cGAMP, preferably in a complex biological sample. As described below, the biosensor of the invention can include a chimeric peptide having a 2′,3′- cGAMP (cGAMP) signal input domain fused with a signal output domain. In this embodiment, 2′,3′-cGAMP binds to the signal input domain causing the activation of the signal input domain. In this embodiment, the signal output domain may include a domain having a known enzymatic activity or other detectable biological function that generates a signal. As a result, the chimeric biosensor can be configured to couple nucleotide concentration, and specifically 2′,3′-cGAMP concentration, to the enzymatic activity or biological function of the output signal domain. In certain embodiment, the enzymatic activity or biological function of the output signal domain can include, but not be limited to nuclease, protease, oligomerization, or other domain functions that can be measured and correlated to the level of 2′,3′-cGAMP in a sample. The invention may include a 2’,3’-cGAMP biosensor comprising a chimeric peptide having two an input and output signal domain, wherein one or both domains include one or more SAVED family receptor domains as generally described herein. In one preferred embodiment, the invention includes a 2’,3’-cGAMP biosensor comprising a chimeric peptide having two an input and output signal domain, wherein one or both domains include a SAVED domain containing protein encoded in an operon with a cGAS / DncV-like nucleotidyltransferase (CD-NTase) from Clade B, as described by Whiteley et al. (See Reference No.8 below, which is incorporated herein by reference in its entirety). In one preferred embodiment, the invention includes a 2’,3’-cGAMP biosensor comprising a chimeric peptide having an input and output signal domain, wherein one or both domains include a CD-NTase enzyme that synthesizes 2’,3’-cGAMP. In another embodiment, the invention includes a 2’,3’-cGAMP biosensor chimeric peptide having native SAVED family receptor protein domain. In this specific embodiment, the “input domain” determines the specificity of the input signal of the construct, in this case by binding to 2’,3’-cGAMP, while the fused “output domain” directs the outcome, or signal output of activation, which in this embodiment includes an endonuclease activity. In this embodiment, the “Chimera10” biosensor peptide of the invention links the binding of 2’,3’-cGAMP to the input domain to nuclease activation of the output domain. In this configuration, the presence of 2’,3’-cGAMP in a sample, and preferably a biological sample binds to the input domain causing activation of the output domain, resulting in endonuclease activity that can be detected through, for example fluorescent DNA probes or simple agarose gel electrophoresis. As noted above, in alternative embodiments, the presence of 2’,3’-cGAMP in a sample, and preferably a biological sample binds to the input domain causing activation of the output domain, resulting in a measurable enzymatic or other chemical action, such as protease activity, oligomerization, or other domain functions that can be measured and correlated to the level of 2′,3′-cGAMP in a sample. As shown in Figure 1, in one embodiment, the 2′,3′-cGAMP biosensor of the invention can include a heterologous nucleotide sequence, operably linked to a promoter, encoding a fusion peptide having an input domain comprising a SAVED005-05 domain from Clostridium botulinum (Cb), and an output domain comprising a HNH12 (sometime referred to as HNHGb) domain from Geobacillus (Gb) sp. Again, as shown in Figure 1, in one embodiment, the 2′,3′-cGAMP biosensor of the invention can include a heterologous nucleotide sequence, operably linked to a promoter, encoding a fusion peptide having an input domain comprising a SAVED005-05 (sometime referred to as SAVEDCb) domain from Clostridium botulinum (Cb) ATCC 17786, and an output domain comprising a HNH12 domain from Geobacillus (Gb) sp. Y4.1MC1. In one embodiment, the 2′,3′-cGAMP biosensor of the invention can include a heterologous nucleotide sequence according to SEQ ID NO.1, operably linked to a promoter, encoding a fusion peptide having an input domain comprising a SAVED005 domain according to the nucleotide sequence SEQ ID NO. 3, or a sequence having 75%, 80-, 85, 90%, 95%, or 99% sequence homology with SEQ ID NO. 3, and a output domain comprising a HNH12 domain according to the nucleotide sequence SEQ ID NO.3, or a sequence having 75%, 80-, 85, 90%, 95%, or 99% sequence homology with SEQ ID NO.2. In one embodiment, the 2′,3′-cGAMP biosensor of the invention can include an amino acid sequence encoding a fusion peptide according to SEQ ID NO. 4, having an input domain comprising a SAVED005 domain according to the sequence SEQ ID NO.6, or a sequence having 75%, 80-, 85, 90%, 95%, or 99% sequence homology with SEQ ID NO.6, and a output domain comprising a HNH12 domain according to the nucleotide sequence SEQ ID NO.5, or a sequence having 75%, 80-, 85, 90%, 95%, or 99% sequence homology with SEQ ID NO.5. Additional aspects of the inventive technology may include embodiments wherein the expression vector encoding a 2′,3′-cGAMP biosensor of the invention is heterologously expressed in a cell, and preferably a eukaryotic cell, such as a yeast, fungi, or animal cell, such as a human cell. In additional embodiment, the 2′,3′-cGAMP biosensor chimeric peptide of the invention may include one or more tag fused to the N-, and / or C-terminal ends of the peptide. In a preferred embodiment, the biosensor may include a 6xhistadine tag (His-6 tag) (SEQ ID NO.9) fused to the N-terminal end of the peptide. In this embodiment, the His-6 tag may be used to isolate and / or purify the chimeric peptide of the invention. For example, the biosensor can be heterologously expressed in a cells, such as a bacterial cell culture. This cell culture may be lysed, and a lysate prepared and passed through a metal ion-charged resin. This lysate may pass through a Ni-charged IMAC resin, where the His-6 tag on the chimeric biosensor peptide may bind to the immobilized nickel ion on the resin. Non-binding and non-specific binding proteins may further be removed in this embodiment through the addition of 5 mM Imidazole, while the chimeric biosensor peptide remains bound to the resin. This His-6, or other tag can be coupled with the chimeric peptide by a linker, such as a two-amino acid sequence of GS, and can further be removed prior to use in detecting 2′,3′-cGAMP. Naturally, this embodiment is exemplary only, as peptide tags and purification procedures would be generally known and applicable by those of ordinary skill in the art. In still further embodiments, the 2′,3′-cGAMP biosensor chimeric peptide of the invention may include one or more tags to increase expression and or other characteristics of the chimeric peptide, such as solubility, and / or protein folding. In this embodiment, the a 2′,3′-cGAMP biosensor chimeric peptide may include a Human Small Ubiquitin-like Modifier (SUMO)2 to 7- amino-4-methylcoumarin (AMC) (hSUMO2) (SEQ ID NO. 10). In this embodiment, the C- terminus of mature hSUMO2 can be coupled to the chimeric biosensor peptide of the invention, for example through a linker, in this case a single Serine amino acid, which can lead to quenching of the intrinsic fluorescence of AMC. Upon incubation with desumoylases, AMC is released and an increase in fluorescence can be measured using at 460 nm (excitation at 380 nm). In this embodiment, the 2′,3′-cGAMP biosensor of the invention can include one or more tags and / or linkers, which can be used to increase yield, as well as identify and purify the exemplary chimeric biosensor peptide (SEQ ID NO. 8, 9) from a complex mixture, such as a bacterial expression extract. In another aspect, the chimeric biosensor protein of the invention includes a modified peptide having a heterologous portion selected from the group consisting of: a signal peptide, a peptide tag, a dimerization domain, an oligomerization domain, an antibody, or an antibody fragment. In still further embodiments the peptide tag is a thioredoxin, Maltose-binding protein (MBP), Glutathione-S-Transferase (GST), calmodulin binding protein (CBP), protein C tag, Myc- tag, Halo-Tag, HA tag, Flag tag, His tag, biotin lag, V5 tag, or OmpA signal sequence tag. In still another embodiment, the antibody fragment is a Fe domain. In yet another embodiment, the polypeptide is immobilized on an object selected from the group consisting of a cell, a metal, a resin, a polymer, a ceramic, a glass, a microelectrode, a graphitic particle, a bead, a gel, a plate, an array, and a capillary tube. Additional embodiments of the inventive technology may include embodiments wherein a 2′,3′-cGAMP biosensor of the invention is encoded by a polynucleotide comprising a nucleic acid sequence. Additional aspects of the inventive technology may include embodiments wherein the chimeric biosensor peptide of the invention is encoded by a polynucleotide which is further linked to a promoter to produce an expression vector. Additional aspects of the inventive technology may include embodiments wherein the expression vector encoding a 2′,3′-cGAMP biosensor of the invention is used to transform a cell, such as a bacterial cell to heterologously express the chimeric biosensor peptide (SEQ ID NO.8, 9) of the invention. The invention includes methods of detecting 2′,3′-cGAMP in a sample, and preferably a biological sample. In this embodiment, a quantity of a chimeric 2′,3′-cGAMP biosensor peptide of the invention can be contacted with a sample containing a quantity of 2′,3′-cGAMP, which can bind to the signal input domain, which as described above, causes activation of the output domain, resulting in a measurable enzymatic or other chemical action, such as protease activity, oligomerization, or other domain functions that can be measured and correlated to the level of 2′,3′-cGAMP in a sample. In a preferred embodiment, a quantity of a chimeric 2′,3′-cGAMP biosensor peptide according to SEQ ID NO.1, or 4, can be contacted with a sample for which a level of 2′,3′-cGAMP is to be determined. In this embodiment, the chimeric biosensor can be incubated in the sample for a period of time, with appropriate positive / negative controls, and the activity of the output signal domain measured at one or multiple time intervals which can be correlated back to establish the level of 2′,3′-cGAMP in a sample. Multiple measurements can be taken over time to establish a change of 2′,3′-cGAMP in a sample, of example after administration of a STING-directed therapeutic compounds, or to determine if a subject would benefit from administration of a STING- directed therapeutic compound. In certain embodiments, the chimeric 2′,3′-cGAMP biosensor peptide can be provided as part of a kit, containing a quantity of isolated biosensor in a container, and instructions for use. As shown in Figure 6, the present inventors demonstrated the measurement of 2 / 3 / -cGAMP in cellular lysates. Specifically, B. subtilis PY79 expressing Empty vector (EV), BtCBASS system, or BtCBASS CdnB-Catalytically dead were grown in 200 ml of LB + phage salts (, and infected with phage SPP1 at an MOI of 2. Cells were harvested 40 minutes post infection, concentrated, and resuspended in 400 µl of water. Bacteria were lysed via bead beating, boiled for 20 minutes, and cellular debris was removed by centrifugation. The supernatant was used for measurement of 2’3’-cGAMP. The procedure include a reaction mixture including: 10 mM Tris-HCl, 25 mM KCl, 1 mM DTT , and 3 µg Chimera10. DNAsealert tube mixed with 5 ml total buffer master mix. Further, 10 µl of cell lysate (described above) was incubated with indicated conditions for 1 hour at 37 °C. Chimera10 activity was measured by monitoring changes in relative fluorescence units (RFU) at the end of the reaction. Chimera10 degrades a fluorescent DNA probe in this reaction in response to 2’3’-cGAMP. Again, as described in Figure 6, Chimera10 displays higher activity, reflecting a higher 2’3’-cGAMP concentration, in lysate derived from WT CdnB expressed during phage infection, as compared to a catalytically dead strain or an empty vector. Unless otherwise defined, all terms of art, notations and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this invention pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and / or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art. The techniques and procedures described or referenced herein are generally well understood and commonly employed using conventional methodology by those skilled in the art, such as, for example, the widely utilized molecular cloning methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 3rd. edition (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. and Current Protocols in Molecular Biology (Ausbel et al., eds., John Wiley & Sons, Inc. 2001. As appropriate, procedures involving the use of commercially available kits and reagents are generally carried out in accordance with manufacturer defined protocols and / or parameters unless otherwise noted. A “fusion” or “chimera” protein is a polypeptide produced when two heterologous nucleotide sequences or fragments thereof coding for two (or more) different polypeptides not found fused together in nature are fused together in the correct translational reading frame. The term “peptide” as used herein, refers to any of various amides that are derived from two or more amino acids by combination of the amino group of one acid with the carboxyl group of another and are usually obtained by partial hydrolysis of proteins. In general, a peptide comprises amino acids having an order of magnitude with the tens. As noted above, the terms protein and peptide also include protein fragments, epitopes, catalytic sites, signaling sites, localization sites and the like. A peptide or protein may further be a fusion or chimera peptide, which a used herein means a peptide having at least a first and second domain or moiety. As described herein, in certain embodiment various peptides, including chimeric peptides or oligonucleotides, such as RNA molecules may be co-expressed. In some embodiments the elements may be co-expressed from a single expression vector having one or more expression cassettes, or from separate expression vectors having one or more expression cassettes. Such expression may also be the result of transient or stable transformation of a cell. As used herein, a “functional” polypeptide or “functional fragment” is one that substantially retains at least one biological activity normally associated with that polypeptide (e.g., nucleosome formation). Unless otherwise stated, nucleic acid sequences in the text of this specification are given, when read from left to right, in the 5′ to 3′ direction. Nucleic acid sequences may be provided as DNA or as RNA, as specified; disclosure of one necessarily defines the other, as is known to one of ordinary skill in the art and is understood as included in embodiments where it would be appropriate. Nucleotides may be referred to by their commonly accepted single-letter codes. Unless otherwise indicated, amino acid sequences are written left to right in amino to carboxyl orientation, respectively. Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols as generally understood by those skilled in the relevant art. The term “fragment,” as applied to a polynucleotide, can further be understood to mean a nucleotide sequence of reduced length relative to a reference nucleic acid or nucleotide sequence and comprising, consisting essentially of, and / or consisting of a nucleotide sequence of contiguous nucleotides identical or almost identical (e.g., at least 90%, 92%, 95%, 98%, 99% identical) to the 25 reference nucleic acid or nucleotide sequence. Such a nucleic acid fragment according to the invention may be, where appropriate, included in a larger polynucleotide of which it is a constituent. In some embodiments, such fragments can comprise, consist essentially of, and / or consist of oligonucleotides having a length of at least about 8, 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 150, 200, or more consecutive nucleotides of a nucleic acid or nucleotide sequence 30 according to the invention. In some embodiments, such fragments can comprise, consist essentially of, and / or consist of oligonucleotides having a length of less than about 8, 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 150, or 200 consecutive nucleotides of a nucleic acid or nucleotide sequence according to the invention. The term “isolated,” when applied to a nucleic acid or protein, denotes that the nucleic acid or protein is essentially free of other cellular components with which it is associated in the natural state. It is preferably in a homogeneous state although it can be in either a dry or aqueous solution. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. A protein which is the predominant species present in a preparation is substantially purified. In particular, a 10 isolated gene is separated from open reading frames which flank the gene and encode a protein other than the gene of interest. The term “purified” denotes that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel. Particularly, it means that the nucleic acid or protein is at least 85% pure, more preferably at least 95% pure, and most preferably at least 99% pure. The term “coupled” or “ligated” when applied to a peptide of the invention may include direct chemical bonds, such as covalent linkages, such as through the generation of fusion or chimera proteins. In alternative embodiment, couple term “coupled” when applied to a peptide of the invention may include instances where a peptide of the invention may be bound to another peptide or molecule through an intermediary compound or molecule, such as a peptide. The terms “conjugating” or “linking” or “coupling” in the context of the present invention with respect to connecting two or more molecules or components to form a complex refers to joining or conjugating said molecules or components, e.g. proteins, via a covalent bond, particularly an isopeptide bond which forms between the peptides that may be mediated by a Cap2 enzyme. A “domain” refers to a unit of a protein or protein complex, comprising a polypeptide subsequence, a complete polypeptide sequence, or a plurality of polypeptide sequences where that unit has a defined function. The function is understood to be broadly defined and can be ligand binding, catalytic activity or can have a stabilizing effect on the structure of the protein. The term “2′,3′-cGAMP biosensor” is used herein to refer to a chimeric peptide of the invention configured to determine the presence of 2′,3′-cGAMP in a sample, preferably a biological sample in vitro or in vivo. A 2′,3′-cGAMP biosensor can include a signal input domain and a signal output domain. As used herein, an “agonist” means a substance, having the function of binding / activating to a receptor or to produce a biological response. A “marker”, or “tag” as used herein, refers to a molecule that can be used for identification, detection, purification, or isolation. In an embodiment, the marker comprises a small molecule, a peptide, a polypeptide, or a labeled amino acid or nucleotide. In an embodiment, the marker generates a signal for detection, e.g., a radioactive signal, a chemiluminescent signal, a fluorescent signal, or a chromogenic signal. For example, the marker is a dye, a fluorophore, a reporter enzyme (e.g., a photoprotein, luciferase), a fluorescent peptide, or a radionuclide. The generated signal can be detected by a variety of assays known in the art, such as fluorescence microscopy, fluorescence- activated cell sorting, gel electrophoresis, and spectrophotometry. The term “signal input domain” sometimes referred to as a “binding domain” or “binding moiety” refers to a protein or protein fragment capable of binding an analyte or ligand, such as 2′,3′-cGAMP. Preferred binding proteins change conformation upon binding the analyte or ligand. “Analyte” or ligand refers to a molecule or ion, such as 2′,3′-cGAMP that binds to the binding protein or domain, causing it to change conformation. Preferably, the analyte or ligand binds reversibly to the binding protein or domain. The term “signal out domain” sometimes referred to as a refers to a protein or protein fragment capable of an enzymatic, chemical or other measurable effect, preferably in response to the binding of a ligand, such as 2′,3′-cGAMP, to the signal input domain As used herein, the term “biological sample” or “sample” includes a sample from any bodily fluid or tissue. Biological samples or samples appropriate for use according to the methods provided herein include, without limitation, blood, serum, urine, saliva, tissues, cells, and organs, or portions thereof. A “subject” is any organism of interest, generally a mammalian subject, and preferably a human subject. As used herein, a compound is referred to as “isolated” when it has been separated from at least one component with which it is naturally associated. For example, a metabolite can be considered isolated if it is separated from contaminants including polypeptides, polynucleotides and other metabolites. Isolated molecules can be either prepared synthetically or purified from their natural environment. Standard quantification methodologies known in the art can be employed to obtain and isolate the molecules of the invention. The term “expression,” as used herein, or “expression” of a coding sequence (for example, a gene or a transgene) refers to the process by which the coded information of a nucleic acid transcriptional unit (including, e.g., genomic DNA or cDNA) is converted into an operational, non- operational, or structural part of a cell, often including the synthesis of a protein. Gene expression can be influenced by external signals; for example, exposure of a cell, tissue, or organism to an agent that increases or decreases gene expression. Expression of a gene can also be regulated anywhere in the pathway from DNA to RNA to protein. Regulation of gene expression occurs, for example, through controls acting on transcription, translation, RNA transport and processing, degradation of intermediary molecules such as mRNA, or through activation, inactivation, compartmentalization, or degradation of specific protein molecules after they have been made, or by combinations thereof. Gene expression can be measured at the RNA level or the protein level by any method known in the art, including, without limitation, Northern blot, RT-PCR, Western blot, or in vitro, in situ, or in vivo protein activity assay(s). The term “nucleic acid” or “nucleic acid molecules” include single- and double-stranded forms of DNA; single-stranded forms of RNA; and double-stranded forms of RNA (dsRNA). The term “nucleotide sequence” or “nucleic acid sequence” refers to both the sense and antisense strands of a nucleic acid as either individual single strands or in the duplex. The term “gene” or “sequence” refers to a coding region operably joined to appropriate regulatory sequences capable of regulating the expression of the gene product (e.g., a polypeptide or a functional RNA) in some manner. A gene includes untranslated regulatory regions of DNA (e.g., promoters, enhancers, repressors, etc.) preceding (up-stream) and following (down- stream) the coding region (open reading frame, ORF) as well as, where applicable, intervening sequences (i.e., introns) between individual coding regions (i.e., exons). A nucleic acid molecule may include either or both naturally occurring and modified nucleotides linked together by naturally occurring and / or non-naturally occurring nucleotide linkages. Nucleic acid molecules may be modified chemically or biochemically, or may contain non-natural or derivatized nucleotide bases, as will be readily appreciated by those of skill in the art. Such modifications include, for example, labels, methylation, substitution of one or more of the naturally occurring nucleotides with an analog, internucleotide modifications (e.g., uncharged linkages: for example, methyl phosphonates, phosphotriesters, phosphoramidates, carbamates, etc.; charged linkages: for example, phosphorothioates, phosphorodithioates, etc.; pendent moieties: for example, peptides; intercalators: for example, acridine, psoralen, etc.; chelators; alkylators; and modified linkages: for example, alpha anomeric nucleic acids, etc.). The term “nucleic acid molecule” also includes any topological conformation, including single-stranded, double-stranded, partially duplexed, triplexed, hairpinned, circular, and padlocked conformations. The term “sequence identity” or “identity,” as used herein in the context of two nucleic acid or polypeptide sequences, refers to the residues in the two sequences that are the same when aligned for maximum correspondence over a specified comparison window. As used herein, the term “percentage of sequence identity” may refer to the value determined by comparing two optimally aligned sequences (e.g., nucleic acid sequences) over a comparison window, wherein the portion of the sequence in the comparison window may comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleotide or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the comparison window, and multiplying the result by 100 to yield the percentage of sequence identity. A sequence that is identical at every position in comparison to a reference sequence is said to be 100% identical to the reference sequence, and vice-versa. Notably, disclosure of a nucleotide sequence also specifically includes with the disclosure its corresponding RNA and amino acid sequence, and vice versa. Polynucleotide sequences may have substantial identity, substantial homology, or substantial complementarity to the selected region of the target gene. As used herein “substantial identity” and “substantial homology” indicate sequences that have sequence identity or homology to each other. Generally, sequences that are substantially identical or substantially homologous will have about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity wherein the percent sequence identity is based on the entire sequence and is determined by GAP alignment using default parameters (GCG, GAP version 10, Accelrys, San Diego, CA). GAP uses the algorithm of Needleman and Wunsch ((1970) J MoI Biol 48:443-453) to find the alignment of two complete sequences that maximizes the number of matches and minimizes the number of sequence gaps. Sequences which have 100% identity are identical. “Substantial complementarity” refers to sequences that are complementary to each other, and are able to base pair with each other. In describing complementary sequences, if all the nucleotides in the first sequence will base pair to the second sequence, these sequences are fully complementary. Methods for aligning sequences for comparison are well-known in the art. Various programs and alignment algorithms are described in, for example: Smith and Waterman (1981) Adv. Appl. Math. 2:482; Needleman and Wunsch (1970) J. Mol. Biol. 48:443; Pearson and Lipman (1988) Proc. Natl. Acad. Sci. U.S.A.85:2444; Higgins and Sharp (1988) Gene 73:237-44; Higgins and Sharp (1989) CABIOS 5:151-3; Corpet et al. (1988) Nucleic Acids Res. 16:10881- 90; Huang et al. (1992) Comp. Appl. Biosci.8:155-65; Pearson et al. (1994) Methods Mol. Biol. 24:307-31; Tatiana et al. (1999) FEMS Microbiol. Lett.174:247-50. A detailed consideration of sequence alignment methods and homology calculations can be found in, e.g., Altschul et al. (1990) J. Mol. Biol. 215:403-10. The National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST™; Altschul et al. (1990)) is available from several sources, including the National Center for Biotechnology Information (Bethesda, Md.), and on the internet, for use in connection with several sequence analysis programs. A description of how to determine sequence identity using this program is available on the internet under the “help” section for BLAST™. For comparisons of nucleic acid sequences, the “Blast 2 sequences” function of the BLAST™ (Blastn) program may be employed using the default BLOSUM62 matrix set to default parameters. Nucleic acid sequences with even greater similarity to the reference sequences will show increasing percentage identity when assessed by this method. As used herein, the term “homologous” with regard to a contiguous nucleic acid sequence, refers to contiguous nucleotide sequences that hybridize under appropriate conditions to the reference nucleic acid sequence. For example, homologous sequences may have from about 70%- 100, or more generally 80% to 100% sequence identity, such as about 81%; about 82%; about 83%; about 84%; about 85%; about 86%; about 87%; about 88%; about 89%; about 90%; about 91%; about 92%; about 93%; about 94% about 95%; about 96%; about 97%; about 98%; about 98.5%; about 99%; about 99.5%; and about 100%. The property of substantial homology is closely related to specific hybridization. For example, a nucleic acid molecule is specifically hybridizable when there is a sufficient degree of complementarity to avoid non-specific binding of the nucleic acid to non-target sequences under conditions where specific binding is desired, for example, under stringent hybridization conditions. Homologs, variants and alleles of the target molecules or proteins of the invention can be identified by conventional techniques. As used herein, a homolog or variant to a polypeptide is a polypeptide from a plant source that has a high degree of structural similarity to the identified polypeptide. The term, “operably linked,” when used in reference to a regulatory sequence and a coding sequence, means that the regulatory sequence affects the expression of the linked coding sequence. “Regulatory sequences,” or “control elements,” refer to nucleotide sequences that influence the timing and level / amount of transcription, RNA processing or stability, or translation of the associated coding sequence. Regulatory sequences may include promoters; translation leader sequences; introns; enhancers; stem-loop structures; repressor binding sequences; termination sequences; polyadenylation recognition sequences; etc. Particular regulatory sequences may be located upstream and / or downstream of a coding sequence operably linked thereto. Also, particular regulatory sequences operably linked to a coding sequence may be located on the associated complementary strand of a double-stranded nucleic acid molecule. As used herein, the term “promoter” refers to a region of DNA that may be upstream from the start of transcription, and that may be involved in recognition and binding of RNA polymerase and other proteins to initiate transcription. A promoter may be operably linked to a coding sequence for expression in a cell, or a promoter may be operably linked to a nucleotide sequence encoding a signal sequence which may be operably linked to a coding sequence for expression in a cell. As used herein, the term “transformation” or “genetically modified” refers to the transfer of one or more nucleic acid molecule(s) into a cell. A microorganism is “transformed” or “genetically modified” by a nucleic acid molecule transduced into the bacteria when the nucleic acid molecule becomes stably replicated by the bacteria. As used herein, the term “transformation” or “genetically modified” encompasses all techniques by which a nucleic acid molecule can be introduced into such a bacteria. The term “vector” refers to some means by which DNA, RNA, a protein, or polypeptide can be introduced into a host. The polynucleotides, protein, and polypeptide which are to be introduced into a host can be therapeutic or prophylactic in nature; can encode or be an antigen; can be regulatory in nature, etc. There are several types of vectors including virus, plasmid, bacteriophages, cosmids, and bacteria. An “expression vector” is nucleic acid capable of replicating in a selected host cell or organism. An expression vector can replicate as an autonomous structure, or alternatively can integrate, in whole or in part, into the host cell chromosomes or the nucleic acids of an organelle, or it is used as a shuttle for delivering foreign DNA to cells, and thus replicate along with the host cell genome. Thus, an expression vector is polynucleotides capable of replicating in a selected host cell, organelle, or organism, e.g., a plasmid, virus, artificial chromosome, nucleic acid fragment, and for which certain genes on the expression vector (including genes of interest) are transcribed and translated into a polypeptide or protein within the cell, organelle or organism; or any suitable construct known in the art, which comprises an “expression cassette.” In contrast, as described in the examples herein, a “cassette” is a polynucleotide containing a section of an expression vector of this invention. The use of the cassettes assists in the assembly of the expression vectors. An expression vector is a replicon, such as plasmid, phage, virus, chimeric virus, or cosmid, and which contains the desired polynucleotide sequence operably linked to the expression control sequence(s). A polynucleotide sequence is operably linked to an expression control sequence(s) (e.g., a promoter and, optionally, an enhancer) when the expression control sequence controls and regulates the transcription and / or translation of that polynucleotide sequence. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions), the complementary (or complement) sequence, and the reverse complement sequence, as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and / or deoxyinosine residues (see e.g., Batzer et al., Nucleic Acid Res. 19:5081 (1991); Ohtsuka et al., J. Biol. Chem. 260:2605-2608 (1985); and Rossolini et al., Mol. Cell. Probes 8:91-98 (1994)). Because of the degeneracy of nucleic acid codons, one can use various different polynucleotides to encode identical polypeptides. As provided below, the table contains information about which nucleic acid codons encode which amino acids. Amino acid Nucleic acid codons Nucleic Acid Amino Acid Codons GCT, GCC, GCA, Ala / A GCG CGT, CGC, CGA, Arg / R CGG,AGA, AGG Asn / N AAT, AAC Asp / D GAT, GAC Cys / C TGT, TGC Gln / Q CAA, CAG Glu / E GAA, GAG GGT, GGC, GGA, Gly / G GGG His / H CAT, CAC Ile / I ATT, ATC, ATA TTA, TTG, CTT, Leu / L CTC, CTA, CTG Lys / K AAA, AAG Met / M ATG Phe / F TTT, TTC CCT, CCC, CCA, Pro / P CCG TCT, TCC, TCA, Ser / S TCG, AGT, AGC ACT, ACC, ACA, Thr / T ACG Trp / W TGG Tyr / Y TAT, TAC GTT, GTC, GTA, Val / V GTG In addition to the degenerate nature of the nucleotide codons which encode amino acids, alterations in a polynucleotide that result in the production of a chemically equivalent amino acid at a given site, but do not affect the functional properties of the encoded polypeptide, are well known in the art. “Conservative amino acid substitutions” are those substitutions that are predicted to interfere least with the properties of the reference polypeptide. In other words, conservative amino acid substitutions substantially conserve the structure and the function of the reference protein. Thus, a codon for the amino acid alanine, a hydrophobic amino acid, may be substituted by a codon encoding another less hydrophobic residue, such as glycine, or a more hydrophobic residue, such as valine, leucine, or isoleucine. Similarly, changes which result in substitution of one negatively charged residue for another, such as aspartic acid for glutamic acid, or one positively charged residue for another, such as lysine for arginine or histidine, can also be expected to produce a functionally equivalent protein or polypeptide. As provided below, the table provides a list of exemplary conservative amino acid substitutions. Conservative amino acid substitutions generally maintain (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a beta sheet or alpha helical conformation, (b) the charge or hydrophobicity of the molecule at the site of the substitution, and / or (c) the bulk of the side chain. Amino Acids and Conservative Substitutes Conservative Amino Acid Substitute Ala Gly, Ser Arg His, Lys Asn Asp, Gln, His Asp Asn, Glu Cys Ala, Ser Gln Asn, Glu, His Glu Asp, Gln, His Gly Ala Asn, Arg, Gln, His Glu Ile Leu, Val Leu Ile, Val Lys Arg, Gln, Glu Met Ile, Leu His, Leu, Met, Phe Trp, Tyr Ser Cys, Thr Thr Ser, Val Trp Phe, Tyr Tyr His, Phe, Trp Val Ile, Leu, Thr Oligonucleotides and polynucleotides that are not commercially available can be chemically synthesized e.g., according to the solid phase phosphoramidite triester method first described by Beaucage and Caruthers, Tetrahedron Letts. 22:1859-1862 (1981), or using an automated synthesizer, as described in Van Devanter et al., Nucleic Acids Res. 12:6159- 6168 (1984). Other methods for synthesizing oligonucleotides and polynucleotides are known in the art. Purification of oligonucleotides is by either native acrylamide gel electrophoresis or by anion- exchange HPLC as described in Pearson & Reanier, J. Chrom. 255:137-149 (1983). Additional methods are known by those of ordinary skill in the art. As used herein, the term “endogenous” refers to any material from or produced inside an organism, cell, tissue or system. As used herein, the term “exogenous” or “heterologous” refers to any material introduced from or produced outside an organism, cell, tissue or system. The term “recombinant” when used with reference, e.g., to a cell, or nucleic acid, protein, or vector, indicates that the cell, organism, nucleic acid, protein or vector, has been modified by the introduction of a heterologous nucleic acid or protein, or the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified. Thus, for example, recombinant cells may express genes that are not found within the native (nonrecombinant or wild-type) form of the cell or express native genes that are otherwise abnormally expressed--over-expressed, under expressed or not expressed at all. The terms “transgenic,” “transformed,” “transformation,” and “transfection” are similar in meaning to “recombinant.” “Transformation,” “transgenic,” and “transfection” refer to the transfer of a polynucleotide into the genome of a host organism or into a cell. Such a transfer of polynucleotides can result in genetically stable inheritance of the polynucleotides or in the polynucleotides remaining extra-chromosomally (not integrated into the chromosome of the cell). Genetically stable inheritance may potentially require the transgenic organism or cell to be subjected for a period of time to one or more conditions which require the transcription of some or all of the transferred polynucleotide in order for the transgenic organism or cell to live and / or grow. Polynucleotides that are transformed into a cell but are not integrated into the host’s chromosome remain as an expression vector within the cell. One may need to grow the cell under certain growth or environmental conditions in order for the expression vector to remain in the cell or the cell’s progeny. Further, for expression to occur the organism or cell may need to be kept under certain conditions. Host organisms or cells containing the recombinant polynucleotide can be referred to as “transgenic” or “transformed” organisms or cells or simply as “transformants,” as well as recombinant organisms or cells. A genetically altered organism is any organism with any change to its genetic material, whether in the nucleus or cytoplasm (organelle). As such, a genetically altered organism can be a recombinant or transformed organism. A genetically altered organism can also be an organism that was subjected to one or more mutagens or the progeny of an organism that was subjected to one or more mutagens and has changes in its DNA caused by the one or more mutagens, as compared to the wild-type organism (i.e., organism not subjected to the mutagens). Also, an organism that has been bred to incorporate a mutation into its genetic material is a genetically altered organism. The terms “approximately” and “about” refer to a quantity, level, value or amount that varies by as much as 30%, or in another embodiment by as much as 20%, and in a third embodiment by as much as 10% to a reference quantity, level, value or amount. As defined herein, with respect to any peptide or genetic sequence the terms “derived from” or “from” means directly isolated or obtained from a particular source or alternatively having identifying characteristics of a substance or organism isolated or obtained from a particular source. In the event that the “source” is an organism, “derived from” or “from” means that it may be isolated or obtained from the organism itself or from the medium used to culture or grow said organism. The use of the word “a” or “an” when used in conjunction with the term ”comprising” in the claims and / or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” The use of the term ”or” in the claims is used to mean “and / or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and / or.” Throughout this application, the term ”about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the study subjects. As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open- ended and do not exclude additional, unrecited elements or method steps. The term ”any combination thereof” as used herein refers to all permutations and combinations of the listed items preceding the term. For example, “A, B, C, or any combinations thereof” is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context. All of the compositions and / or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and / or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims. TABLES Table 1. 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[0002] SEQUENCE LISTING SEQ ID NO.1 DNA Chimera 10 (HNH12 Endonuclease-SAVED005-05) Artificial GCTCGCGATGCCTTTAAATTGTCGACTATCGACGACCGTGCATTGTGGGTAGCCAGCGGCGGAATGTGTG CTAAGTGTAAGCGTGTCCTTATCTTCGACGATATTGAACGTAAAGTAAATCTGGGGGAACGTGCTCATAT CATCGGTAAGGGCGATGGTAAGAACGCGCCACGCCGCGAGTTCGCAGAGGAGTACGGGATCACTGAAGAA AATATCGATTCACTGATGAATTTGATGCTTATGTGCAAGGAGTGTCACCATATTATCGATACTAATGTAA AACAGTACCCGCCAGACGTGCTGTTTGATATGAAAGAAAAGCATGAGTCTTGGGTGATGTCTCGCTTGTC CCAAAATAAAATTAAACTGTTGAATATTCAAGCGTATTCAGACAATAGCCTTCAAAATTTTGAAAAAAGC GAGTACAAATTAAATTTGACGGAGGCCGAGTATATTGATCTGGTGGAAACTTGGCGCATTACAAATAGTC GCGGTTATCAACACTGTGATTTTAAGGACGATATTAAGAATATCATTAACAAGATCCGTGAGCAGACGTT AGCGTTCAAAAGCTCTTCCCGTGGCTATAAACGCGCGTTTATGGGAATTGTGCCTATCCCATTCTTGATC TATATGGGCTCCATCATTCCAAAGCTGAAGTTCTCCGAGTATCTTGAGATCCAAAACCGTAACTCTAATA AGTTAATTTTGTTGGATACGACAGGTACGATTAAGTATAGTCCCTTACAGATCCGCGGGGATTTTAATAA TAGTAACAAGGACGACGAGATCATTATCGCCGTCTCAACGACGGCTCAAATCGGCGACTACAATTTAGTA CAGTTCACGAATCGCCAAATCGATATTCGTCATATTTATTTGAAGGAACCTGGACACGGTGCTATCATCA GCGTAGACCAAATTAACAATTATGCGGAAACGATCATCGAAGAAATCCTTTCTATCCGCCGTATCAAACA TAACCTTAAAACCGTACACCTGATCTGCGCCTCGAAACCGTCCTTGGTTTTCCGTCTGGGGCAACTGATT GACAACAACACACAACTGCCAATCATTATCAGTTACCAGCAAAACCAGGGCGGCCAAATTGAATATCCGT GGGGGATTTATATCAACCACCCTCAGAAACAAGGTCAAGCTGTGTTGTGGGATGACCTG SEQ ID NO.2 DNA Chimera 10 (HNH12 Endonuclease) Artificial GCTCGCGATGCCTTTAAATTGTCGACTATCGACGACCGTGCATTGTGGGTAGCCAGCGGCGGAATGTGTG CTAAGTGTAAGCGTGTCCTTATCTTCGACGATATTGAACGTAAAGTAAATCTGGGGGAACGTGCTCATAT CATCGGTAAGGGCGATGGTAAGAACGCGCCACGCCGCGAGTTCGCAGAGGAGTACGGGATCACTGAAGAA AATATCGATTCACTGATGAATTTGATGCTTATGTGCAAGGAGTGTCACCATATTATCGATACTAATGTAA AACAGTACCCGCCAGACGTGCTGTTTGATATGAAAGAAAAGCATGAGTCTTGGGTGATGTCTCGCTTGTC CCAAAATAAA SEQ ID NO.3 DNA Chimera 10 (SAVED005-05) Artificial ATTAAACTGTTGAATATTCAAGCGTATTCAGACAATAGCCTTCAAAATTTTGAAAAAAGCGAGTACAAAT TAAATTTGACGGAGGCCGAGTATATTGATCTGGTGGAAACTTGGCGCATTACAAATAGTCGCGGTTATCA ACACTGTGATTTTAAGGACGATATTAAGAATATCATTAACAAGATCCGTGAGCAGACGTTAGCGTTCAAA AGCTCTTCCCGTGGCTATAAACGCGCGTTTATGGGAATTGTGCCTATCCCATTCTTGATCTATATGGGCT CCATCATTCCAAAGCTGAAGTTCTCCGAGTATCTTGAGATCCAAAACCGTAACTCTAATAAGTTAATTTT GTTGGATACGACAGGTACGATTAAGTATAGTCCCTTACAGATCCGCGGGGATTTTAATAATAGTAACAAG GACGACGAGATCATTATCGCCGTCTCAACGACGGCTCAAATCGGCGACTACAATTTAGTACAGTTCACGA ATCGCCAAATCGATATTCGTCATATTTATTTGAAGGAACCTGGACACGGTGCTATCATCAGCGTAGACCA AATTAACAATTATGCGGAAACGATCATCGAAGAAATCCTTTCTATCCGCCGTATCAAACATAACCTTAAA ACCGTACACCTGATCTGCGCCTCGAAACCGTCCTTGGTTTTCCGTCTGGGGCAACTGATTGACAACAACA CACAACTGCCAATCATTATCAGTTACCAGCAAAACCAGGGCGGCCAAATTGAATATCCGTGGGGGATTTA TATCAACCACCCTCAGAAACAAGGTCAAGCTGTGTTGTGGGATGACCTG SEQ ID NO.4 Amino Acid Chimera 10 (HNH12 Endonuclease-SAVED005-05) Artificial ARDAFKLSTIDDRALWVASGGMCAKCKRVLIFDDIERKVNLGERAHIIGKGDGKNAPRREFAEEYGITEE NIDSLMNLMLMCKECHHIIDTNVKQYPPDVLFDMKEKHESWVMSRLSQNKIKLLNIQAYSDNSLQNFEKS EYKLNLTEAEYIDLVETWRITNSRGYQHCDFKDDIKNIINKIREQTLAFKSSSRGYKRAFMGIVPIPFLI YMGSIIPKLKFSEYLEIQNRNSNKLILLDTTGTIKYSPLQIRGDFNNSNKDDEIIIAVSTTAQIGDYNLV QFTNRQIDIRHIYLKEPGHGAIISVDQINNYAETIIEEILSIRRIKHNLKTVHLICASKPSLVFRLGQLI DNNTQLPIIISYQQNQGGQIEYPWGIYINHPQKQGQAVLWDDL SEQ ID NO.5 Amino Acid Chimera 10 (HNH12 Endonuclease) Artificial ARDAFKLSTIDDRALWVASGGMCAKCKRVLIFDDIERKVNLGERAHIIGKGDGKNAPRREFAEEYGITEE NIDSLMNLMLMCKECHHIIDTNVKQYPPDVLFDMKEKHESWVMSRLSQNK SEQ ID NO.6 Amino Acid Chimera 10 (SAVED005-05) Artificial IKLLNIQAYSDNSLQNFEKSEYKLNLTEAEYIDLVETWRITNSRGYQHCDFKDDIKNIINKIREQTLAFK SSSRGYKRAFMGIVPIPFLIYMGSIIPKLKFSEYLEIQNRNSNKLILLDTTGTIKYSPLQIRGDFNNSNK DDEIIIAVSTTAQIGDYNLVQFTNRQIDIRHIYLKEPGHGAIISVDQINNYAETIIEEILSIRRIKHNLK TVHLICASKPSLVFRLGQLIDNNTQLPIIISYQQNQGGQIEYPWGIYINHPQKQGQAVLWDDL SEQ ID NO.7 DNA Chimera 10 (Full-Tagged) Artificial ATGGGTTCTTCTCACCATCACCATCACCATGGTTCAGGAGTCAAGACTGAGAACAACGATCATATTAATT TGAAGGTGGCGGGGCAGGATGGTTCTGTGGTGCAGTTTAAGATTAAGAGGCATACACCACTTAGTAAACT AATGAAAGCCTATTGTGAACGACAGGGATTGTCAATGAGGCAGATCAGATTCCGATTTGACGGGCAACCA ATCAATGAAACAGACACACCTGCACAGTTGGAAATGGAGGATGAAGATACAATTGATGTGTTTCAACAGC AGACGGGTGGATCCGCTCGCGATGCCTTTAAATTGTCGACTATCGACGACCGTGCATTGTGGGTAGCCAG CGGCGGAATGTGTGCTAAGTGTAAGCGTGTCCTTATCTTCGACGATATTGAACGTAAAGTAAATCTGGGG GAACGTGCTCATATCATCGGTAAGGGCGATGGTAAGAACGCGCCACGCCGCGAGTTCGCAGAGGAGTACG GGATCACTGAAGAAAATATCGATTCACTGATGAATTTGATGCTTATGTGCAAGGAGTGTCACCATATTAT CGATACTAATGTAAAACAGTACCCGCCAGACGTGCTGTTTGATATGAAAGAAAAGCATGAGTCTTGGGTG ATGTCTCGCTTGTCCCAAAATAAAATTAAACTGTTGAATATTCAAGCGTATTCAGACAATAGCCTTCAAA ATTTTGAAAAAAGCGAGTACAAATTAAATTTGACGGAGGCCGAGTATATTGATCTGGTGGAAACTTGGCG CATTACAAATAGTCGCGGTTATCAACACTGTGATTTTAAGGACGATATTAAGAATATCATTAACAAGATC CGTGAGCAGACGTTAGCGTTCAAAAGCTCTTCCCGTGGCTATAAACGCGCGTTTATGGGAATTGTGCCTA TCCCATTCTTGATCTATATGGGCTCCATCATTCCAAAGCTGAAGTTCTCCGAGTATCTTGAGATCCAAAA CCGTAACTCTAATAAGTTAATTTTGTTGGATACGACAGGTACGATTAAGTATAGTCCCTTACAGATCCGC GGGGATTTTAATAATAGTAACAAGGACGACGAGATCATTATCGCCGTCTCAACGACGGCTCAAATCGGCG ACTACAATTTAGTACAGTTCACGAATCGCCAAATCGATATTCGTCATATTTATTTGAAGGAACCTGGACA CGGTGCTATCATCAGCGTAGACCAAATTAACAATTATGCGGAAACGATCATCGAAGAAATCCTTTCTATC CGCCGTATCAAACATAACCTTAAAACCGTACACCTGATCTGCGCCTCGAAACCGTCCTTGGTTTTCCGTC TGGGGCAACTGATTGACAACAACACACAACTGCCAATCATTATCAGTTACCAGCAAAACCAGGGCGGCCA AATTGAATATCCGTGGGGGATTTATATCAACCACCCTCAGAAACAAGGTCAAGCTGTGTTGTGGGATGAC CTG SEQ ID NO.8 Amino Acid Chimera 10 (Full-Tagged) Artificial MGSSHHHHHHGSGVKTENNDHINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQP INETDTPAQLEMEDEDTIDVFQQQTGGSARDAFKLSTIDDRALWVASGGMCAKCKRVLIFDDIERKVNLG ERAHIIGKGDGKNAPRREFAEEYGITEENIDSLMNLMLMCKECHHIIDTNVKQYPPDVLFDMKEKHESWV MSRLSQNKIKLLNIQAYSDNSLQNFEKSEYKLNLTEAEYIDLVETWRITNSRGYQHCDFKDDIKNIINKI REQTLAFKSSSRGYKRAFMGIVPIPFLIYMGSIIPKLKFSEYLEIQNRNSNKLILLDTTGTIKYSPLQIR GDFNNSNKDDEIIIAVSTTAQIGDYNLVQFTNRQIDIRHIYLKEPGHGAIISVDQINNYAETIIEEILSI RRIKHNLKTVHLICASKPSLVFRLGQLIDNNTQLPIIISYQQNQGGQIEYPWGIYINHPQKQGQAVLWDD L SEQ ID NO.9 Amino Acid His-6-Tag Artificial MGSSHHHHHH SEQ ID NO.10 Amino Acid hSUMO Artificial GVKTENNDHINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEM EDEDTIDVFQQQTGG LEGEND: serine linker = underlined HNH12 Endonuclease sequence (AA1-120) = Italics SAVED005-05 sequence (AA114-386) = BOLD

Claims

CLAIMS What is claimed is:

1. A biosensor comprising: ^ a chimeric peptide having: - a 2′,3′-cGAMP (cGAMP) signal input domain; - a signal output domain; and - wherein said signal output domain is activated through the binding of cGAMP to the signal input domain.

2. The biosensor of claim 1, wherein said signal input domain and / or said signal output domain comprises all or part of a SAVED family receptor domain.

3. The biosensor of claim 1, wherein said signal input domain and / or said signal output domain comprise a SAVED domain containing all or part of a protein encoded in an operon with a cGAS / DncV-like nucleotidyltransferase (CD-NTase) 4. The biosensor of claim 1, wherein said signal input domain and / or said signal output domain comprise all or part of a CD-NTase enzyme that synthesizes 2’,3’-cGAMP.

5. The biosensor of claim 1, wherein said signal output domain comprises a nuclease domain activated through the binding of cGAMP to the signal input domain.

6. The biosensor of claim 1, wherein said signal input domain comprises a SAVED005-05 (SAVEDCb) domain from Clostridium botulinum.

7. The biosensor of claim 1, wherein said signal input domain comprises a peptide according to amino acid sequence SEQ ID NO.6, or a sequence having at least 90% sequence homology with SEQ ID NO.6.

8. The biosensor of claim 1, wherein said signal output domain comprise a signal output domain having an output signal selected from the group consisting of: nuclease activity, protease activity, and oligomerization activity.

9. The biosensor of claim 1, wherein said signal output domain comprise a HNH12 domain from Geobacillus sp. (HNHGb).

10. The biosensor of claim 1, wherein said signal output domain comprise a peptide according to amino acid sequence SEQ ID NO.5, or a sequence having at least 90% sequence homology with SEQ ID NO.

5.

11. The biosensor of claim 1, wherein said: ^ signal output domain comprise a HNHGbdomain; and ^ signal input domain comprises a SAVEDCb domain.

12. The biosensor of claim 1, wherein said: ^ signal input domain comprises a peptide according to amino acid sequence SEQ ID NO.6, or a sequence having at least 90% sequence homology with SEQ ID NO.6; ^ signal output domain comprise a peptide according to amino acid sequence SEQ ID NO.5, or a sequence having at least 90% sequence homology with SEQ ID NO.

5.

13. The biosensor of any of claims 1-12 further comprising a tag.

14. The biosensor of claim 13 wherein said tag comprises a Hi-6-tag and / or a hSUMO2 tag.

15. A biosensor comprising: ^ a chimeric peptide having: - a 2′,3′-cGAMP (cGAMP) signal input domain according to SEQ ID NO.6; - a signal output domain according to SEQ ID NO.5; and - wherein said signal output domain is activated through the binding of cGAMP to the signal input domain.

16. A 2′,3′-cGAMP (cGAMP) biosensor comprising a chimeric peptide according to SEQ ID NO.

4.

17. A 2′,3′-cGAMP (cGAMP) biosensor comprising a chimeric peptide according to SEQ ID NO.

8.

18. A method of detecting 2′,3′-cGAMP (cGAMP) comprising: ^ contacting a sample with the biosensor of any of claims 1-17; ^ measuring the activity of the signal output domain; ^ correlating the level of the activity of the signal output domain with a level of cGAMP in a sample.

19. The method of claim 18, wherein said sample comprises a biological sample.

20. The method of claim 18 ,wherein said biological sample comprises a biological sample from a subject.

21. The method of claim 18, wherein said sample comprises a bacterial sample.

22. The method of claim 18, wherein said activity of the signal output domain comprises nuclease activity.

23. The method of claim 22, wherein said nuclease activity is detected by fluorescent DNA probes, and / or gel electrophoresis.

24. A nucleotide sequence, operably linked to a promoter, encoding a biosensor comprising: ^ a chimeric peptide having: - a 2′,3′-cGAMP (cGAMP) signal input domain; - a signal output domain; and- wherein said signal output domain is activated through the binding of cGAMP to the signal input domain.

25. The biosensor of claim 24, operably linked to a promoter, encoding a 2′,3′-cGAMP (cGAMP) biosensor according to SEQ ID NO.

1.

26. The biosensor of claim 24, operably linked to a promoter, encoding a 2′,3′-cGAMP (cGAMP) biosensor according to SEQ ID NO.

7.

27. The biosensor of claim 24, wherein said signal input domain and / or said signal output domain comprises all or part of a SAVED family receptor domain.

28. The biosensor of claim 24, wherein said signal input domain and / or said signal output domain comprise a SAVED domain containing all or part of a protein encoded in an operon with a cGAS / DncV-like nucleotidyltransferase (CD-NTase) 29. The biosensor of claim 24, wherein said signal input domain and / or said signal output domain comprise all or part of a CD-NTase enzyme that synthesizes 2’,3’-cGAMP.

30. The biosensor of claim 24, wherein said signal output domain comprises a nuclease domain activated through the binding of cGAMP to the signal input domain.

31. The biosensor of claim 24, wherein said signal input domain comprises a SAVED005-05 (SAVEDCb) domain from Clostridium botulinum.

32. The biosensor of claim 24, wherein said signal input domain comprises a peptide according to amino acid sequence SEQ ID NO.3, or a sequence having at least 80% sequence homology with SEQ ID NO.3.

33. The biosensor of claim 24, wherein said signal output domain comprise a signal output domain having an output signal selected from the group consisting of: nuclease activity, protease activity, and oligomerization activity.

34. The biosensor of claim 24, wherein said signal output domain comprise a HNH12 domain from Geobacillus sp. (HNHGb).

35. The biosensor of claim 24, wherein said signal output domain comprise a peptide according to amino acid sequence SEQ ID NO.2, or a sequence having at least 80% sequence homology with SEQ ID NO.

2.

36. The biosensor of claim 24, wherein said: ^ signal output domain comprise a HNHGbdomain; and ^ signal input domain comprises a SAVEDCb domain.

37. The biosensor of claim 24, wherein said: ^ signal input domain comprises a peptide according to amino acid sequence SEQ ID NO.6, or a sequence having at least 90% sequence homology with SEQ ID NO.3; and ^ signal output domain comprise a peptide according to amino acid sequence SEQ ID NO.5, or a sequence having at least 90% sequence homology with SEQ ID NO.

2.

38. The biosensor of any of claims 24-37, further comprising a tag.

39. The biosensor of claim 38 wherein said tag comprises a Hi-6-tag 40. The biosensor of claim 38 wherein said tag comprises a hSUMO2 tag.

41. A cell expressing a heterologous nucleotide sequence of any of claims 24-40.

42. The cell of claim 41, wherein said cell comprises a prokaryotic cell.

43. The cell of claim 42, wherein said prokaryotic cell comprises a bacterial cell.

44. The cell of claim 43, wherein said bacterial cell comprises an E. Coli cell.

45. A kit for detecting 2’,3’-cGAMP comprising a biosensor chimeric peptide of any claim above, a container, and instructions for use.

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