46 results about "Type three secretion system" patented technology

A modified P. aeruginosa type III secretion system has been developed that efficiently delivers selected proteins into a host cell. In one example, a functional nuclear Cre Recombinase is injected into embryonic stem (ES) cells and can be used to induce pluripotent stem (iPS) cells. This method of in vitro lineage directed differentiation prevents insertional mutagenesis and provides a route to selected stem cell renewal and cell-based therapies.

This invention provides methods of treating patients having a Staphylococcus infection where the patient also has a low level of Pseudomonas aeruginosa. The methods comprise administering an antagonist of the Pseudomonas Type III Secretion System, e.g., an anti-PcrV antibody antagonist.

The invention relates to the use of the type III secretion system of bacteria to stimulate immune responses against tumor antigen(s) for treating antigen-loss variant tumors. Methods are provided for stimulating and / or increasing an immune response against tumor antigens. The invention also relates to the preparation of antigen presenting cells from peripheral blood mononuclear cells using bacteria having a type III secretion system.

The present invention provides a vector for expression of a chimeric protein which is the result of the fusion between the N-terminal end of ExoS of Pseudomonas aeruginosa and an amino acid sequence of interest, the N-terminal end of ExoS corresponding to the N-terminal end of the chimeric protein. The vector contains the following from 5′ to 3′:a promoter,a nucleic acid comprising a nucleotide sequence encoding at least the 48 (SEQ ID 4) and at the most the 96 (SEQ ID 6) amino acids of the N-terminal end of ExoS; or any sequence of the same size that is at least 70% identical thereto and that has a secretion activity at the same level as that of ExoS,a nucleic acid comprising a nucleotide sequence encoding the amino acid sequence of interest.

The present invention provides compositions and methods for the secretion and the translocation of a compound of interest by a bacterial minicell. In certain embodiments, the invention provides a bacterial minicell comprising at least one component of the type III secretion system (T3SS), which provides a safe and efficient system for secretion and translocation. In one embodiment, the invention allows for the delivery of an antigen to a cell or subject in order to induce an immune response.

The invention discloses a tumor vaccine using attenuated salmonella as a vector and a preparation method thereof.Active component of the tumor vaccine is recombinant attenuated salmonella, the construction method of the recombinant attenuated salmonella includes the following steps: 1) an expression vector for expressing recombinant prokaryotic cell of confusion protein is constructed; the confusion protein comprises a N side signal area (namely a N side guiding secretion area[1]) of effect proteins(SPI-2 TTSS) in a III-type secretion system of salmonella and at least a protein antigen or a protein epitope of the tumor; the expression vector of the recombinant prokaryotic cell is obtained by introducing encoding gene of the confusion protein into multiple cloning sites of the expression vector of the prokaryotic cell; 2) the expression vector of the recombinant prokaryotic cell is introduced to the attenuated salmonella to obtain the recombinant attenuated salmonella expressing the confusion protein. The tumor vaccine in the invention can be used for preventing the tumor.

The present invention pertains to Bordetella bacteria having a double mutation, a first mutation in a gene of the Type III secretion system and a second mutation in a gene of the adenylate cyclase toxin (CyaA) locus of the bacteria so that the mutations result in no Type III secretion system, a non-functional Type III secretion system, no CyaA protein, or a non-functional CyaA protein or a combination thereof. The Bordetella bacteria double mutant is attenuated while maintaining the efficacy of the bacteria to elicit an immune response. The present invention also pertains to vaccine compositions and methods for treating and immunizing a mammal against a disease caused by infection of Bordetella bacteria or a disease caused by a pathogen.

A means for decreasing bacterial virulence in a mammal including man or in a plant by inhibition of the Type III secretion system at concentrations that do not prevent or substantially reduce bacterial growth comprises an N-substituted 7-quinolylmethyl amine, in particular one that is further substituted in 5- and 8-position on the quinoline ring. A corresponding therapeutic method and a pharmaceutical composition are also disclosed.

The invention belongs to an agricultural bactericide, and concretely relates to a report system applied to a plant pathogenic bacterium type III secretion system, and an application thereof. The system comprises a report pathogen and a report vector, wherein the report pathogen contains the plant pathogenic bacterium type III secretion system, and the report vector is an expression vector containing beta-lactamase synthesis gene and a type III secretion system signal peptide. The invention provides a brand new high-flux screening method for screening type III secretion system inhibitors based on the interaction of beta-lactamase and a chromogenic substrate nitrocefin. The bacterium type III secretion system is artificially induced to express, a report vector gene product is transferred to the outside of a cell, and reacts with the chromogenic substrate, and whether the type III secretion system is inhibited or not is judged according to the color change. Secondary amine type III secretion system inhibitors are found by using the method.

Disclosed are compositions and methods for expressing and purifying a peptide of interest using a Flagellar Type III secretion system. Disclosed are nucleic acid sequences that contain a FlgM nucleic acid sequence, a cleavage site, and a nucleic acid sequence of interest. Also disclosed are polypeptides that contain FlgM, a cleavage site and a peptide of interest. Methods of producing polypeptides that have FlgM, a cleavage site and a peptide of interest are provided.

Disclosed is a newly identified and characterized type III secretion system in Aeromonas salmonicida. The invention also encompasses the use of components of the novel secretion system in immunoprotection against A. salmonicida infection, as well as other diagnostic and therapeutic uses thereof.

The invention relates to a construction method and applications of engineering strain for delivering mammalian cell protein. The construction method comprises the following steps: deleting four virulence factors including exoS, exoT, exoY and ndk genes from pseudomonas aeruginosa PAK strain genome, so as to have no cytotoxicity to mammalian cells; further deleting popN gene, for inhibiting bacterial III type secretory system (T3SS), from chromosome, so as to remarkably increase the injection quantity of T3SS-mediated protein, thus constructing the engineering strain delta5. The constructed engineering strain delta5 can be used for delivering proteins of various mammalian cell linings, performing gene editing, cell reprogramming, protein function research and other work. The types of delivered cells are wide, including human and mice skin cells, muscle cells, intestinal cells, liver cells, multipotent stem cells and the like.

The invention relates to application of myricanol in preparing a drug for resisting bacterial virulence. The structural formula of a compound 1 is shown in the description. The myricanol is a diarylheptanoids compound, and has a function of significantly inhibiting the secretion of virulence proteins of a salmonella type III secretion system (T3SS). The inhibitor does not inhibit the growth of salmonella, but inhibits the invasion of host cells by the salmonella, and therefore the compound can be used for preparing the drug for resisting the virulence of Gram-negative bacteria.

The invention discloses a complementary deoxyribonucleic acid (cDNA) sequence related to iron deficiency of a plant and an encoded protein and application thereof. A full-length cDNA of a ZmFDR gene is cloned from an iron-deficient induced corn root and the structural characteristic of the full-length cDNA and the functional complementation of the full-length cDNA in yeast are analyzed. The analysis of the structural characteristic indicates that the full length of the ZmFDR gene is 3.3 kb, the gene comprises two open reading frames which are 1,068 bp and 648 bp respectively and the latter is named as ZmFDR4 (SEQ ID NO:1). The encoded protein (SEQ ID NO:2) has four transmembrane domains and has a signal peptide which belongs to a secretory protein and has a similar structure domain to a Flip protein in an III type secretory system. Extensive homology comparison indicates that no homology sequence is found in a higher plant. A yeast functional complementation experiment proves that the expression of the cDNA sequence in the yeast can transfer iron ions effectively.

The invention discloses a substituted phenyl furan-2-mercaptothiazoline ketone compound as well as a preparation method and application thereof. The structure of the compound is as shown in a structural formula (III). The invention also discloses a preparation method and application of the compound. The substituted phenyl furan-2-mercaptothiazoline ketone compound provided by the invention is novel in structure, simple in preparation method and high in yield; the compound has an obvious inhibiting effect on an xanthomonas oryzae pv III type secretory system (T3SS), and can be taken as a xanthomonas oryzae pv T3SS activity inhibitor, especially a compound III-7, which does not affect growth of xanthomonas oryzae pv while pathogenicity of the xanthomonas oryzae pv is reduced, so that pathogenic bacteria can be prevented from generating drug resistance, and the effects of preventing and / or controlling the xanthomonas oryzae pv also can be achieved. (The formula is as shown in specification.).

The invention relates to a building method of attenuated pseudomonas aeruginosa and application of the attenuated pseudomonas aeruginosa to protein transfection. The building method is characterized in that glutamate racemase gene murI participating in cell wall peptidoglycan synthesis in a pseudomonas aeruginosa Delta8 bacterial strain is deleted, so that a D-glutamate nutritional deficiency typebacterial strain Delta9 is obtained. According to the application, the Delta9 bacterial strain has no cytotoxicity; the complete III type secretory system (T3SS) is reserved; foreign protein is effectively injected into mammalian cells through T3SS and can be applied to mammalian cell protein transfection. The Delta9 cannot grow in culture environment lacking D-glutamate, so that after the transfection, the bacterium is automatically cleared through D-glutamate nutrient limitation. The in vitro and in vivo application safety of the bacterium is interpreted by using HeLa cells and a mouse infection model. The positive significance is realized for developing the safe and efficient mammalian cell protein transfection technology.

The invention discloses (S)-1,3-thiazolyl phenyl furan thioformate compounds and a preparation method and application thereof. The compounds have a strong inhibitory effect on a hpa1 gene promoter ina pathogen T3SS system, and the inhibition rate of some compounds exceeds 97%, and the compounds can be used as a T3SS system inhibitor; some of the compounds strongly inhibit the plant pathogen T3SSsystem, does not affect the growth of plant pathogenic bacteria meanwhile, but only significantly reduces the pathogenicity of the plant pathogenic bacteria to achieves the prevention and / or treatmentof plant diseases caused by the plant pathogenic bacteria; the compounds can be used as a plant pathogen type III secretion system inhibitor, or used for preparing a drug for related the plant diseases for preventing and / or treating the plant diseases, also have the effect of reducing and delaying the resistance of the plant pathogenic bacteria to the compounds, and have a longer effective life for prevention and / or treatment of the plant diseases and broad application prospects..

This invention provides methods of treating patients having a Staphylococcus infection where the patient also has a low level of Pseudomonas aeruginosa. The methods comprise administering an antagonist of the Pseudomonas Type III Secretion System, e.g., an anti-PcrV antibody antagonist.

The present invention relates to a recombinant bacterium expressing an antigen that is translocated to the cytosol of a host organism, and uses thereof. To this end, the present invention provides a recombinant bacterium comprising a nucleic acid encoding an antigen that is translocated to the cytosol of a host cell utilizing Type III secretion system. The recombinant bacterium is generally chosen from intracellular pathogens that reside in the phagosome and fail to induce rapid T cell activation. The translocated antigen may be a viral antigen, a bacterial antigen, or a tumour antigen. Methods of imparting immunity using the recombinant bacterium are also provided.

A modified P. aeruginosa type III secretion system has been developed that efficiently delivers selected proteins into a host cell. In one example, a functional nuclear Cre Recombinase is injected into embryonic stem (ES) cells and can be used to induce pluripotent stem (iPS) cells. This method of in vitro lineage directed differentiation prevents insertional mutagenesis and provides a route to selected stem cell renewal and cell-based therapies.

Organic compounds showing the ability to inhibit effector toxin secretion or translocation mediated by bacterial type III secretion systems are disclosed. The disclosed type III secretion system inhibitor compounds are useful for combating infections by Gram-negative bacteria such as Salmonella spp., Shigella flexneri, Pseudomonas spp., Yersinia spp., enteropathogenic and enteroinvasive Escherichia coli, and Chlamydia spp. having such type III secretion systems.

Salmonella enteric serotype Typhimurium is a causative agent for gastroenteritis. It is the leading cause of hospitalization and death caused by a food-borne pathogen in the US. As is the case with many gram- negative pathogens, Salmonella spp. use type III secretion systems (T3SS) to deliver proteins to host cells to induce infections. The T3SS uses a molecular syringe and needle, the type III secretion apparatus (T3SA), as a conduit for the transport of the T3SS proteins from the bacteria to the host. Because proteins associated with the tip of the T3SA are extracellular, they are potential protective subunit vaccine candidates against Salmonella. These pathogens also have a T3SS that is involved with intracellular escape from the vacuole with an associated T3SA. Within this invention, we begin to show proof of concept that these proteins are protective.

The invention provides recombinant protein. The recombinant protein is formed by fusion of a PA III type secretory system component protein (PcrV) fragment and a PA outer membrane lipoprotein (OprI) fragment through a Linker, and has a general formula: PcrV fragment-(Linker)n-Oprl fragment, wherein the sequence of the Linker is selected from one of GGGGS, GGSGG and YAPVDV, and preferentially GGGGS; n is 1, 2, 3 or 4, and preferentially 1. The invention also provides a preparation method and an application of the recombinant protein. Subunit vaccine prepared from the recombinant protein can stimulate the organism to generate high-titer IgG antibodies; the recombinant protein can be used for preparing diagnostic reagents, and preventive or therapeutic drugs.

Organic compounds showing the ability to inhibit effector toxin secretion or translocation mediated by bacterial type III secretion systems are disclosed. The disclosed type III secretion system inhibitor compounds are useful for combating infections by Gram-negative bacteria such as Salmonella spp., Shigella flexneri, Pseudomonas spp., Yersinia spp., enteropathogenic and enteroinvasive Escherichia coli, and Chlamydia spp. having such type III secretion systems.

This invention relates generally to molecules that specifically bind bacterial V-tip proteins of the type III secretion system of Gram negative bacteria such as PcrV from Pseudomonas aeruginosa. More specifically, this invention relates to molecules that block the injection of effector molecules into target cells. This invention also relates to molecules that specifically bind to bacterial lipoproteins, such as OprI. The molecules of the present invention are monospecific or multispecific and can bind their target antigen in a monovalent or multivalent manner. The invention also relates generally to molecules that specifically bind bacterial cell surface proteins such as OprI, and to methods of use these molecules in a variety of therapeutic, diagnostic, and / or prophylactic indications.

The present invention relates to a recombinant bacterium expressing an antigen that is translocated to the cytosol of a host organism, and uses thereof. To this end, the present invention provides a recombinant bacterium comprising a nucleic acid encoding an antigen that is translocated to the cytosol of a host cell utilizing Type III secretion system. The recombinant bacterium is generally chosen from intracellular pathogens that reside in the phagosome and fail to induce rapid T cell activation. The translocated antigen may be a viral antigen, a bacterial antigen, or a tumour antigen. Methods of imparting immunity using the recombinant bacterium are also provided.

The invention discloses an application of cinnamylic acid compound in preventing and / or treating plant diseases. The compound of the invention can strongly inhibit the virulence factors of the plant pathogen without affecting the growth of the plant pathogen, and significantly reduce the pathogenicity of the plant pathogen, that is, without affecting the growth of the plant pathogen, the prevention and / or treating of the plant diseases caused by plant pathogens can be achieved; the compound can be used as a plant pathogen type-III secretion system inhibitor or as a drug for controlling the related plant diseases for preventing and / or treating plant diseases, also has the effect of reducing and delaying the resistance of the plant pathogen to the compound, has a long effective use period inthe prevention and / or treatment of plant diseases, and has a broad application prospect.

An object is to provide an antibody and a vaccine composition which have an ability to practically prevent or treat a Pseudomonas aeruginosa infection, and which can cope with the diversity of clinical isolates derived from patients infected with Pseudomonas aeruginosa. According to the present invention, an antibody against a PA1698 protein that is a type III secretion system component protein of Pseudomonas aeruginosa or against a peptide of the protein, and a vaccine composition comprising the protein or the peptide are provided.