25 results about "Cryptococcus gattii" patented technology

The invention discloses a cryptococcus capsular polysaccharide detection kit. The cryptococcus capsular polysaccharide detection kit comprises a biotin-labeled cryptococcus monoclonal antibody and an acridinium ester-labeled cryptococcus monoclonal antibody, wherein the biotin-labeled cryptococcus monoclonal antibody and the acridinium ester-labeled cryptococcus monoclonal antibody are coupled with streptavidin magnetic beads. According to the cryptococcus capsular polysaccharide detection kit disclosed by the invention, the biotin-labeled cryptococcus monoclonal antibody coupled with the streptavidin magnetic beads and the acridinium ester-labeled cryptococcus monoclonal antibody are matched, so that the cryptococcus capsular polysaccharide detection kit has relatively strong recognition capability on various serotypes of cryptococcus, and the antibodies do not interfere with one another; according to the cryptococcus capsular polysaccharide detection kit, the detection sensitivity and the detection accuracy can be greatly improved, the problem that a detection result is greatly influenced by subjective consciousness and is inaccurate due to the fact that an existing detection method only depends on visual inspection is solved, and the cryptococcus capsular polysaccharide detection kit is convenient to operate, facilitates automatic operation of an instrument and reduces manual errors.

The application provides an application of a compound HEX and / or a compound POM-HEX in medicine for preventing and / or treating fungal infection, and belongs to the technical field of medicine. In vitro experiments show that POM-HEX alone has inhibiting effects on candida and cryptococcus, and when combined with fluconazole, the antifungal activity can be significantly improved, and the drug-resistant strains can restore the sensitivity to fluconazole. The organ bacterial load experiment in mice in vivo proves that POM-HEX can stably exert the drug efficacy in the organism. In addition, the IC 50 value of the metabolic product HEX of POM-HEX for inhibiting the Eno1 enzyme activity of Candida albicans is 1 / 30 of the IC 50 of HEX for inhibiting the Eno1 enzyme activity of human. The application discloses that the HEX and / or the compound have strong antifungal activity and high selectivity for the target point Eno1, provides a new idea for antifungal treatment, the drug combination can reduce the drug dosage, reduce the toxic and side effects, and solves the problem of fungal drug resistance.

The application discloses application of gynostemma pentaphyllum saponin H combined with azole drugs in preparation of antifungal drugs and the antifungal drugs, and relates to the technical field of antifungal drugs. It is found through systematic in-vitro drug sensitivity test that natural product gynostemma pentaphyllum saponin H combined with specific azole antifungal drugs (especially posaconazole POS) can produce significant synergistic antifungal effect, especially for clinical thorny aspergillus, candida, new cryptococcus and dark fungi. The combination strategy can significantly reduce the minimum inhibitory concentration of azole drugs, reverse drug resistance, and is effective for multi-drug resistant strains (such as candida auris). The application provides an efficient and low-toxicity new combination drug scheme for overcoming the increasingly serious fungal drug resistance problem.

This invention belongs to the field of fungal detection technology, specifically relating to a micro-platform for rapid electrolysis and highly sensitive electrochemical nucleic acid detection of Cryptococcus neoformans and its application. The micro-platform includes an integrated microfluidic chip, an external power supply, a sample introduction system, and / or an imaging system. The integrated microfluidic chip includes an electrolysis region, an electrochemical detection region, and an electrode array region. The electrolysis region includes multiple vertically arranged counter electrodes arranged in pairs, and multiple horizontally arranged hollow channels in a serpentine pattern, bonded to the electrode pairs above them. The connection point between every two electroporated channels is the electroporation lysis point. The electrochemical detection region consists of a working electrode, a reference electrode, and a counter electrode. The working electrode is modified with rGO / AuNPs nanomaterials and molecular probes.

Provided are a combination of an inositol phosphorylceramide synthase inhibitor and amphotericin B and use thereof. The use includes preparing a pharmaceutical composition, which includes an inositol phosphorylceramide synthetase inhibitor and amphotericin B or a salt thereof. Inositol phosphorylceramide is an important and conserved component of fungal plasma membranes. In the pharmaceutical composition according to an embodiment of the present disclosure, due to the presence of the inositol phosphorylceramide synthase inhibitor, the interaction between the inositol phosphorylceramide synthase inhibitor and amphotericin B not only enhances the inhibitory ability of the inositol phosphorylceramide synthase inhibitor on the synthesis of inositol phosphorylceramide in Cryptococcus, but also effectively reduces the dosage of amphotericin B and prolongs the half-life of amphotericin B, facilitating to reduce the adverse reactions of amphotericin B. The pharmaceutical composition exhibits superior fungicidal effect and safety compared to the currently used clinical combination of 5-fluorocytosine and amphotericin B.

The application discloses a biosynthesis gene cluster of a polyene macrolide natural product mandimycin, and a natural product and application of the biosynthesis gene cluster, wherein the nucleotide sequence of the biosynthesis gene cluster is shown as SEQ ID NO. 1, and the compound structural formula of the natural product mandimycin and mandimycin B is shown as formula I and formula II. The natural product mandimycin can target fungal cell membrane phospholipid molecules, especially phosphatidylinositol, cause important ion efflux in fungal cells, and lead to fungal cell death. The natural product mandimycin and mandimycin B have strong in-vivo and in-vitro antibacterial activity and a broad antibacterial spectrum on various WHO-published multiple drug-resistant fungal key pathogens, including candida, aspergillus, cryptococcus, mucor and fusarium.

The invention relates to a five-membered heteroaryl compound and application thereof, the compound is a compound with a structural formula shown in the specification or pharmaceutically acceptable salts and prodrugs thereof, in the formula, R1 is selected from CH3 and H; r2 is selected from NH2 and OH; r3 is selected from CH3 and H; r4 is selected from OH, F and H; r5 is selected from NO2 and H; r6 is selected from CN, NO2 and H; and L1 is selected from-CH2O <-> and-CH2-CH2 <->, and-CH is equal to CH <->. A series of five-membered heteroaryl compounds are researched and developed on the basis of an APX001A structure, and the five-membered heteroaryl compounds have a good Gwtl protein binding effect and can inhibit Gwtl protein activity, so that GPI-AP synthesis is prevented, mannose glycoprotein on the fungal surface cannot be cross-linked to a cell wall, the host surface adhesion capacity and cell wall integrity of the mannose glycoprotein are destroyed, the antifungal effect is achieved, and the application prospect is broad. The compound has good inhibitory activity on candida, cryptococcus and aspergillus.

The application provides a set of primers and probes for detecting invasive fungi, reagents and application thereof, a kit and a detection method, and relates to the technical field of biology.The nucleic acid sequence of the primer is shown as SEQ ID NO.1-2, 4-5, 7-11, 14-15, 17-18 and 20-21; and the nucleic acid sequence of the probe is shown as SEQ ID NO.3, 6, 12-13, 16, 19 and 22.The primers and probes have high specificity and sensitivity, and can be used for the detection and identification of Aspergillus, Mucorales, Cryptococcus neoformans, Pneumocystis jirovecii and Lichtheimia. The kit for detecting invasive fungi has high specificity and sensitivity, and wide fungal coverage, and can realize the detection of multiple invasive fungi simultaneously.

The invention discloses a composition, a kit and a detection method for detecting pulmonary infection pathogens. The composition comprises at least one of a component A, a component B, a component C and a component D, the component A comprises a primer pair SEQ ID NO: 1-2 and a probe SEQ ID NO: 3; detecting bordetella pertussis by the component A; the component B comprises a primer pair SEQ ID NO: 4-5 and a probe SEQ ID NO: 6; the component B is used for detecting Nocardia; the component C comprises a primer pair SEQ ID NO: 7-8 and a probe SEQ ID NO: 9; detecting cryptococcus neoformans by the component C; the component D comprises a primer pair SEQ ID NO: 10 to 11 and a probe SEQ ID NO: 12; the component D is used for detecting acinetobacter baumannii. The composition for detecting the pulmonary infection pathogens provided by the invention can detect and distinguish at least one of bordetella pertussis, nocardia, cryptococcus neoformans and acinetobacter baumannii, has higher sensitivity, specificity and precision, can accurately and quickly detect bordetella pertussis, nocardia, cryptococcus neoformans and acinetobacter baumannii, and can be used for detecting the pulmonary infection pathogens. The detection efficiency is improved, the detection period is shortened, and detection is convenient.

The application relates to a kind of five-membered heteroaryl antifungal compounds and its application, the structural formula of the compound is as shown below:;Wherein, Ar is selected from the group consisting of,, and,;R1 It is selected from F and H;R2 It is selected from F and H;R3 It is selected from NO2, CN and H;R4 It is selected from CN and H;R5 It is selected from CN, F and H;L1 It is selected from-CH2O-, -OCH2- and-O-;T1 It is selected from N and CH.The application develops a series of five-membered heteroaryl compounds on the basis of APX001A structure, has good Gwt1 protein binding, can inhibit Gwt1 protein activity, thereby prevent GPI-AP synthesis, lead to the surface of fungi mannose protein cannot be crosslinked on cell wall, further destroy its adhesion host surface ability and cell wall integrity, play antifungal effect, have good inhibitory activity to candida, cryptococcus and aspergillus.

The present application belongs to the field of biotechnology and medicine, and relates to a centromere binding protein Cbf1, a coding gene thereof and application. Specifically, the present application provides a Cryptococcus virulence related protein, which is a centromere binding protein Cbf1. Meanwhile, the present application also provides application of the centromere binding protein Cbf1 in preparation of a medicine, CBF1 Gene knockout leads to reduction of tolerance of the strain to 37 DEG C, oxidation and cell wall pressure, and reduction of melanin production, so that the protein can be used as a drug target and applied to research and development of a new drug for treating diseases caused by Cryptococcus.

The invention specifically discloses a risk biomarker for cryptococcus meningitis and application thereof, and relates to the technical field of biological medicines. The invention provides a brand new cryptococcus brain infection antivirulence factor mitochondrial citric acid transporter: by closing the mitochondrial citric acid transporter, glucose metabolism hijacking in the brain is realized, and the colonization advantage is obtained.

The present invention provides a fungal drug carrier comprising an avirulent fungal pathogen cell, for example a Cryptococcus neoformans cell, linked to one or more surface-bound drug-loaded nanoparticles, and methods of making the fungal drug carrier. The invention provides methods of using the fungal drug carrier to deliver a drug to the central nervous system of a patient, wherein the fungal drug carrier is phagocytosed by an immune cell of a patient, transported across the blood-brain barrier, and vomocytosed to allow drug release from the surface-bound nanoparticle into the central nervous system of the patient. The methods involve treating a central nervous system in a patient comprising administering to the patient a pharmaceutical composition comprising a fungal drug carrier.

This invention provides a novel target PDE4B for the prevention and treatment of Cryptococcus neoformans brain infection. Specifically, it relates to the application of drugs targeting phosphodiesterase PDE4B in the preparation of drugs for the prevention and / or treatment of Cryptococcus neoformans meningoencephalitis. The drug targeting PDE4B is the PDE4B agonist MR-L2 (CAS: 2374703-19-0). The PDE4B agonist MR-L2 described in this invention can significantly reduce Cryptococcus neoformans brain infection, providing an effective prevention and treatment method for Cryptococcus neoformans meningoencephalitis.

The invention discloses a novel medical application of sodium new houttuyfonate in prevention and treatment of pathogenic bacteria, including application of sodium new houttuyfonate in preparation of drugs for prevention and treatment of pathogenic fungus infection or drugs for inhibition of pathogenic fungi. The pathogenic fungi are selected from one or more of cryptococcus neoformans, cryptococcus gattii, trichophyton rubrum, trichophyton purple, microsporum canis, candida niticola complex bacteria, candida albicans, trichophyton mentagrophytes and trichophyton broken. Researches show that sodium new houttuyfonate has important significance in preventing and treating infection of different pathogenic bacteria, especially has a remarkable curative effect on cryptococcus neoformans lung infectious diseases and skin traumatic infectious diseases, and compared with traditional antibacterial drugs, the sodium new houttuyfonate is not prone to causing drug resistance of pathogenic bacteria and has a good application prospect. The compound is expected to be developed into a candidate drug for clinically treating different pathogenic bacteria, is efficient, non-toxic and broad-spectrum, is expected to solve the problem of drug resistance of the pathogenic bacteria, and has a good application prospect.

This invention discloses a broad-spectrum antibacterial composition derived from Syzygium sima (Syzygium sima) and its preparation method, relating to the field of biomedical technology. The composition comprises an active ingredient and pharmaceutically acceptable excipients. The active ingredient includes ursane-type triterpenoids or their pharmaceutically acceptable salts, esters, or prodrugs. The active ingredient provided by this invention exhibits potent inhibitory activity against a variety of clinically common pathogenic fungi, particularly showing significant antibacterial effects against Candida albicans, Cryptococcus neoformans, Candida glabrata, Aspergillus fumigatus, and Aspergillus niger. This compound is a natural product with an ursane-type triterpenoid skeleton, featuring a structure with α-L-rhamnose linked at C-3 and a free carboxyl group retained at C-28, overcoming the shortcomings of some existing plant-derived antibacterial agents, such as narrow antibacterial spectrum and poor efficacy against specific fungi.

The invention relates to the field of medicines, in particular to a compound and application thereof. The compound is shown as a formula I, and also comprises pharmaceutically acceptable salts, prodrugs, tautomers, stereoisomers, isotope derivatives or solvates of the compound. The compound disclosed by the invention has good antifungal activity, particularly has exact and excellent inhibition and antibacterial activity on candida, cryptococcus and rhizopus arrhizus, and also has excellent antibacterial activity on voriconazole drug-resistant bacteria. The compound can be used for preventing and / or treating various diseases caused by fungal infection.

The application discloses a black seabream antibacterial peptide AS-hepc3 (48‑56) application in preparing anti-cryptococcus neoformans composition. The application detects the black seabream antibacterial peptide AS-hepc3 (48‑56) antibacterial activity on the cryptococcus neoformans CGMCC2.1563 and the cryptococcus neoformans H99, analyzes the drug resistance of the cryptococcus neoformans H99 to the AS-hepc3 (48‑56) , and determines that the black seabream antibacterial peptide AS-hepc3 (48‑56) has the anti-cryptococcus neoformans activity, and lays a foundation for developing natural peptide anti-cryptococcus neoformans drugs.

The invention relates to the technical field of medical examination molecular diagnosis, and particularly discloses a fluorescence PCR (Polymerase Chain Reaction) detection method for cryptococcus neoformans. A group of brand new specific primers (CN-F and CN-R) and a TaqMan probe (CN-P) are designed aiming at a cryptococcus neoformans ITS1 + 5.8 S + ITS2 + LSUrRNA gene region, and an internal standard system taking barley Dhn10 gene as a template is introduced to carry out whole-process monitoring. The detection method of the integrated UDG anti-pollution system is established by optimizing and determining the optimal concentration ratio of the primer probe and the reaction procedure. The method has the advantages of high sensitivity, high specificity, excellent precision and excellent clinical inclusiveness, can be used for 100% detection of new cryptococcus neoformans variants, Glubii variants and heterozygotes thereof, and provides a reliable tool for rapid and accurate clinical diagnosis of cryptococcus neoformans infection.

Conjugates of amphotericin B and gold nanoparticles stabilized with thiohexoses or thiopentoses, and a method to produce said nanoparticles are described. As the conjugates of amphotericin B to the stabilized gold nanoparticles show several advantages over amphotericin B alone, pharmaceutical compositions comprising said nanoparticles, and to their use for treat fungal and leishmanial infection are described. These amphotericin B stabilized gold nanoparticles are dispersible in water and are not toxic for mammalian cells differently from free amphotericin B and other currently used amphotericin B preparations. Importantly, the conjugates of amphotericin B and stabilized gold nanoparticles are more efficacious in treating all forms of Cryptococcal infections (planktonic, intracellular and biofilms) than amphotericin B.

The invention relates to an oligonucleotide combination and kit for detecting and distinguishing cryptococcus. The oligonucleotide combination comprises a specific primer, a guide chain and a reporter probe, wherein the specific primer, the guide chain and the reporter probe are designed aiming at a cryptococcus neoformans CAP59 gene and a cryptococcus gattii GPA1 gene. The kit comprises the oligonucleotide combination, pfAgo enzyme, divalent manganese ions and a reaction buffer solution, and can be used for non-diagnostic purpose detection. The method comprises the following steps: carrying out asymmetric PCR amplification on a sample DNA to obtain a single-chain product, incubating the single-chain product with pfAgo enzyme, a guide chain and a reporter probe together to carry out a cleavage reaction, and finally distinguishing the cryptococcus species through fluorescence signals (such as FAM and ROX). The method has the advantages of high specificity and sensitivity (the lower detection limit reaches 1CFU / mL), no cross reaction, short detection time (about 60 minutes), accurate verification in clinical cerebrospinal fluid samples, and suitableness for rapid identification of cryptococcus.

This invention discloses a NO donor-type antifungal compound, its preparation method, and its application. The compound is represented by general formula V. By introducing a nitric oxide (NO) donor fragment into an active azole antibacterial fragment, it achieves the effect of dose-dependent slow release of nitric oxide in the presence of a thiol-containing nucleophilic reagent in vitro. When applied to antifungal drugs, the above compound can inhibit fungal growth at low concentrations and has broad-spectrum antibacterial activity. It has a strong inhibitory effect on Candida albicans, Candida glabrata, and Cryptococcus neoformans, and is also effective against cryptococcal meningitis caused by invasive Cryptococcus neoformans.

The application discloses application of gamma-ambroin in prevention and treatment of plant fungal diseases and human fungal diseases. In rice blast fungus filter paper piece plate activity screening, the inhibition rate of gamma-ambroin on the rice blast fungus is 51.40%, and the activity is much higher than that of alpha-ambroin, berberine, hesperidin, eugenol and emodin methyl ether. The EC 50 50 of gamma-ambroin against the rice blast fungus is 293.55 muM, which is lower than the EC 50 50 of berberine and kasugamycin. In addition, gamma-ambroin shows inhibition activity on various plant pathogenic fungi, and can relieve pepper anthracnose disease. Meanwhile, it is found through detection that gamma-ambroin has strong inhibition activity on Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus, and the MIC is 3.9-62.5 muM. In view of the high fungal inhibition activity and green safety characteristics of gamma-ambroin, the gamma-ambroin can be used in green prevention and control of plant fungal diseases and prevention of human pathogenic fungi.

A direct PCR detection method for trace colonies of Cryptococcus neoformans with gene mutations, belonging to the field of molecular biology detection technology, addresses the problems of existing technologies that require genomic DNA extraction, resulting in cumbersome steps and difficulty in handling trace samples. The method involves picking the Cryptococcus neoformans transformants to be tested, suspending them in PCR buffer, heating at 94°C for 12-15 minutes for thermal lysis, and then cooling on ice for 5-8 minutes for stability. Taq DNA polymerase, dNTPs, and primers are then directly added to the original PCR tube to prepare a complete PCR reaction system for amplification and electrophoresis detection. This invention eliminates the need for DNA extraction, purification, and sample transfer throughout the entire process, making it simple, fast, and cost-effective, especially suitable for single colonies or 10 colonies. 3 ~10 4 The experiment, which uses extremely small amounts of bacterial cells at the cell level, has a high success rate and can be completed in just 1-2 hours, making it highly valuable for high-throughput gene mutation screening and verification.