141 results about "Cryptococcus neoformans" patented technology

The present invention provides C. neoformans genes that are essential and are potential targets for drug screening. The nucleotide sequence of the target genes can be used for various drug discovery purposes, such as expression of the recombinant protein, hybridization assay and construction of nucleic acid arrays. The uses of proteins encoded by the essential genes, and genetically engineered cells comprising modified alleles of essential genes in various screening methods are also encompassed by the invention. The present invention also provides methods and compositions that enable the experimental determination as to whether any gene in the genome of Cryptococcus neoformans is essential, and whether that gene is required for virulence or pathogenicity. The identification of essential genes and those genes critical to the development of virulent infections, provides a basis for the development of screens for new drugs against C. neoformans.

Vaccines and methods of inoculation for conferring immunity to Cryptococcus infection are disclosed. Strains of Cryptococcus fungi, including Cryptococcus neoformans and Cryptococcus gattii, can be administered to a human or animal subject via inhalation. Cryptococcus fungi that can be used to confer immunity can comprise one or more mutations in genes that contribute to chitosan production, such as genes encoding a chitin deacetylase (cda), a chitin synthase (chs) and / or a regulator of chitin synthase (csr). Inhalation administration of heat-killed Cryptococcus harboring deletions in cda1, cda2 and cda3 genes can confer immunity. In a murine model system, inhalation administration of Cryptococcus neoformans harboring deletions in cda1, cda2 and cda3 genes conferred immunity against subsequent exposure to wild type Cryptococcus neoformans in 100% of test animals. Inhalation administration of heat-killed Cryptococcus grown under conditions leading to reduced chitosan production can also confer immunity.

The antifungal and cancer cell growth inhibitory activities of 1-(3′,4′,5′-trimethoxyphenyl)-2-nitro-ethylene (TMPN) were examined. TMPN was fungicidal for the majority of 132 reference strains and clinical isolates tested, including those resistant to fluconazole, ketoconazole, amphotericin B or flucytosine. Minimum fungicidal concentration / minimum inhibitory concentration (MFC / MIC) ratios were ≦2 for 96% of Cryptococcus neoformans clinical isolates and 71% of Candida albicans clinical isolates. TMPN was fungicidal for a variety of other basidiomycetes, endomycetes and hyphomycetes, and its activity was unaffected by alterations in media pH. TMPN was slightly cytotoxic for murine and human cancer cell lines (GI50=1-4 μg / ml), and weakly inhibited mammalian tubulin polymerization (IC50=0.60 μg / ml). TMPN may also be used as a biochemical probe for tubulin and fungal dimorphism studies.

The invention discloses a cow leather mat with an anti-bacterial function. The cow leather mat is characterized in that a grain side and a flesh side of the cow leather mat simultaneously comprises a nano-silver and isothiazolinone antibacterial agent; the inhibition zone of the nano-silver and isothiazolinone antibacterial agent to staphylococcus aureus, colon bacillus, bacillus subtilis, Aspergillus niger, blue mould, hair mould, cryptococcus neoformans, candida albicans is 43.28 to 68.84mm; the dry wipe resistance level is 4 to 5 level or 5 level; the wet wipe resistance level is 3 to 4 level or 4 level; and folding resistance fastness is 1 level. The invention also discloses a preparation method of the cow leather mat. The cow leather mat not only has good inhibit function to bacterium and fungus, but also has durable antibacterial property; the preparation method is skillful, the only thing to do is to add antibacterial treatment after a middle layer is coated, additional investment cannot be increased, the process is simple to operate, and the cow leather mat is applicable to industrial application.

The invention relates to a triple nucleic acid test kit. The kit comprises a thallus lysate, a positive quantitative reaction liquid, a negative control reaction liquid and a thallus test reaction liquid, wherein the thallus test reaction liquid contains specific primers, specific probes and doping fluorescent dye for aspergillus, Cryptococcus neoformans and candida albicans, the three specific oprimers are designed according to areas of ITS sequences of aspergillus, Cryptococcus neoformans and candida albicans, FAM, VIC and CY-5 are selected for mark report groups of the three specific probes, MGB serves as a quenching group, the excitation wavelength of the FAM group is 492 nm, and the emission wavelength is 517 nm; the excitation wavelength of the VIC group is 557 nm and the emission wavelength is 574 nm; the excitation wavelength of the CY-5 group is 646 nm and the emission wavelength is 664 nm. The triple nucleic acid test kit for aspergillus, Cryptococcus neoformans and candida albicans can assist in diagnosing infection caused by aspergillus, Cryptococcus neoformans and candida albicans.

The invention relates to the fungal polysaccharide preparation field, and concretely relates to a preparation method of Cryptococcus Neoformans capsular polysaccharide. The invention provides a method for preparing the Cryptococcus Neoformans capsular polysaccharide through utilizing cetyl trimethyl ammonium bromide. The method comprises the following steps: 1, processing a secretion supernatant containing the capsular polysaccharide through using calcium acetate and glacial acetic acid, and precipitating through using ethanol to prepare a crude capsular polysaccharide; and 2, processing a solution of the crude capsular polysaccharide through using the cetyl trimethyl ammonium bromide to obtain the purified capsular polysaccharide. The method has the advantages of simplicity, high efficiency, low cost, and effective avoiding of the use of toxic and harmful chemical reagents.

The invention relates to a nucleic acid reagent, kit, system and method for detecting invasive fungi. The nucleic acid reagent comprises a primer shown in SEQ ID NO.1-14 and a probe shown in SEQ ID NO.17-26, and the primer and the probe are stored independently with each other correspondingly or mixed with each other at will. Through the primer and the probe, the nucleic acid reagent, the kit, thesystem and the method of at least 9 invasive fungi of candida albicans, candida tropicalis, candida glabrata, candida parapsilosis, mucor, aspergillus, cryptococcus neoformans, pneumocystis jeroveciand candida auris, fast, comprehensive, sensitive, specific and automatic detection result determination can be achieved, and the sensitivity, specificity, simplicity and convenience of simultaneous detection of the detection target genome are significantly improved.

The invention belongs to the technical field of medicine, and more specifically provides applications of nicotinamide in preparing an antifungal drug synergist. Novel applications of nicotinamide are provided; nicotinamide is capable of reducing dosages of antifungal drugs such as azoles, echinocandins, and polyenes as an antifungal drug synergist, and reducing toxic and side effect of drugs, especially fluconazole, voriconazole, caspofungin, and amphotericin B, accordingly. Nicotinamide is capable of recovering the effect of antifungal drugs on drug resistance funguses as a antifungal drug synergist, treating fungal infection especially drug resistance fungus infection effectively, reducing drug toxicity, and reducing economic burden of patients in drug therapy; and in addition, nicotinamide is capable of improving the effect of antifungal drugs on candida tropicalis and cryptococcus neoformans, and possesses high clinical application value.

The invention relates to a novel wide-spectrum bacterial strain Bacillus sp. AH-E-1 inhibiting clinical and plant pathogenic fungi, and an application thereof. The main content comprises: (1) Bacillus sp. AH-E-1 is a newly-discovered bacillus strain or subspecies; (2) Bacillus sp. AH-E-1 can produce anti-fungus substances after fermentation under appropriate conditions; (3) Bacillus sp. AH-E-1 can significantly inhibit 20 clinical pathogenic fungi such as aspergillus flavus, aspergillus fumigates, trichophyton rubrum, trichophyton mentagrophyte, candida glabrata, cryptococcus neoformans, and the like; (4) Bacillus sp. AH-E-1 can significantly inhibit 13 plant pathogenic fungi such as staphylococcus, magnaporthe oryzae, rhizopusstolonife, and the like. The invention provides an excellent novel anti-fungus substance producing bacterial strain which has the advantages of wide fungus-inhibiting spectrum, obvious effect, and the like.

The invention discloses a fungus rapid culture, identification and susceptibility detection kit for rapidly and effectively identifying multiple fungi and testing the susceptibility. The invention also discloses a method for directly detecting a clinical sample by using the kit. The kit has the advantages that the multiple fungi are simultaneously identified and different pores are favorable for growing different fungi by coating various sugars or inhibitors on a susceptibility test board, so that the most common fungi in clinic use, such as candida albicans, candida tropicalis, candida glabrata, candida krusei, cryptococcus neoformans, candida guilliermondii and the like, can be identified and effective guidance is provided for the clinical use. The detection method is simple and suitable for detecting pure fungi, can be further directly applied to fungus identification of the clinical sample and the susceptibility detection of antibiotics and has a short detection period, namely thefungi to be detected can be simultaneously identified and the susceptibility can be detected at one time and the result can be given in 24 hours; and thus the detection method greatly shortens the clinical detection period and is favorable for early diagnosis and early therapy of patients.

The invention discloses 3-aryl-4-arylamino-2 (5(i)H( / i))-furanone compounds, which are characterized in that the compounds have the following structural general formulas: in formula I, if R1=R3=Br, Cl or OCH3 and R2=R4=R5=R6=R8=H, R7=NO2, F, Cl, Br, OCH3 or OH; if R2=F, Cl, Br, OH, NO2 or OCH3 and R1=R3=R4=R5=R6=R8=H, R7=NO2, F, Cl, Br, OCH3 or OH; if R1=R3=Br, Cl or OCH3 and R2=R4=R5=R6=R8=H, R6=NO2, F, Cl, Br, OCH3 or OH; if R2=F, Cl, Br, OH, NO2 or OCH3 and R1=R3=R4=R5=R8=H, R6=R7=OCH3 or OH; and R1=R3=Br, Cl or OCH3 and R2=R4=R5=R8=H, R6=R7=OCH3 or OH. The compounds of the invention have preferable inhibition effects on staphylococcus epidermidis, Klebsiella pneumoniae, Cryptococcus neoformans and the like, and can be used for preparing anti-infective drugs for treating pneumonia, septic wounds and the like. The invention discloses a preparation method of the compounds.

The compositions and methods described herein discloses the design, synthesis and testing of compounds that act as inhibitors of DHFR. The basic scaffold of these inhibitors includes a 2,4-diaminopyrimidine ring with a propargyl linker to another substituted aryl, bicyclo or heteroaryl ring. These DHFR inhibitors are potent and selective for many different pathogenic organisms, including the DHFR enzyme from bacteria such as Bacillus anthracis and methicillin-resistant Staphylococcus aureus, fungi such as Candida glabrata, Candida albicans and Cryptococcus neoformans and protozoa such as Cryptosporidium hominis and Toxoplasma gondii. These compounds and other similar compounds are also potent against the mammalian enzyme and may be useful as anti-cancer therapeutics.

The invention provides a polyclonal antibody of a GXM (glucuronoxylomannan) antigen of Cryptococcus neoformans. The polyclonal antibody is prepared through the following steps: inactivated Crytococcus Neoformans bacteria are taken as an immunogen immunized animal, separated and purified, and a primarily purified polyclonal antibody is obtained; the GXM antigen of Cryptococcus neoformans is cross-linked with an affinity chromatography substrate, and a GXM immunoaffinity chromatography column of Cryptococcus neoformans is obtained; after the primarily purified polyclonal antibody is purified with the immunoaffinity chromatography column, the polyclonal antibody resisting the GXM antigen of Cryptococcus neoformans is obtained. The polyclonal antibody prepared with the method has the characteristics of high titer and high purity and has broad application prospect in the fields of medical treatment and scientific research.

The invention discloses a kit and method for multi-fold fluorescence quantitation detection of cryptococcus neoformans and aspergilli. The invention provides a multi-fold fluorescence quantification reagent for detecting the cryptococcus neoformans and the aspergilli, and the method comprises the following steps of detecting a primer 1 of the cryptococcus neoformans, detecting a primer 2 of the cryptococcus neoformans, detecting a probe 1 of the cryptococcus neoformans, detecting a primer 3 of the aspergilli, detecting a primer 4 of the aspergilli and detecting a probe 2 of the aspergilli. The experiments of the invention prove that the kit and detection method disclosed by the invention are based on multi-fold Taqman fluorescence quantitation detection technology, not only can rapidly make certain of contained pathogens, reduce detection costs and improve the utilization rate of an instrument, but also solve the flux problem of detection of the pathogens contained in clinical respiratory tract fungus, thereby having important guiding significance in early clinical diagnosis and treatment.

The invention discloses use of rhizoma paridis chinensis for preparing an antifungal drug, belonging to the technical field of medicines. In-vitro cell experiments show that rhizoma paridis chinensishas different levels of antifungal effects and even fungus-killing effect to drug-resistant candida albicans 103, candida albicans SC5314, cryptococcus neoformans, candida krusei, candida parapsilosis, candida glabrata and candida tropicalis and therefore can be taken as the antifungal drug. According to the use, new use of rhizoma paridis chinensis is opened up, rhizoma paridis chinensis is usedfor preparing the antifungal drug, and a new candidate drug is provided for the treatment of fungal infection. Currently, drugs with wide antifungal spectrums and fungus-killing activity on clinic arevery few, and a new way is provided for the clinical and efficient treatment of infection of fungi and even drug-resistant fungi by virtue of the characteristics of wide antifungal spectrums and fungus-killing activity of rhizoma paridis chinensis under the conditions that clinical fungus drug resistance becomes common increasingly and the drug resistance level becomes serious increasingly.

The invention provides a triazole compound shown as a general formula (I), optical isomers or the pharmaceutically acceptable salts thereof, and application of the compound, optical isomers or pharmaceutically acceptable salts thereof to preparation of medicaments for resisting fungi, especially Candida albicans, Candida parapsilosis, Candida glabrata, Cryptococcus neoformans, Microsporum flavescens, Trichophyton rubrum and / or Aspergillus fumigatus. The invention provides a pharmaceutical composition, comprising a therapeutically effective amount of one or more selected from the compound shown in the formula (I), optical isomers and pharmaceutically acceptable salts thereof and pharmaceutic adjuvants.

The invention provides a gene chip for detecting common pathogenic bacteria in cosmetics. The gene chip comprises a solid phase carrier and an oligonucleotide probe fixed on the solid phase carrier, wherein the oligonucleotide probe comprises DNA segments which are selected from 16S-23SrDNA intermediate zones of micrococcus luteus, staphylococcus aureus, streptococcus pyogenes, salmonella, proteus mirabilis, citrobacter freundii, pseudomonas aeruginosa, enterobacter aerogenes and providencia stuartii and 18S-28SrDNA intermediate zones of the ipaH gene of shigella, candida albicans and cryptococcus neoformans, or complementary DNA or RNA sequences of the DNA segments. The invention also provides a kit for detecting the common pathogenic bacteria in the cosmetics by use of the gene chip. The gene chip and the kit can be used for detecting the common pathogenic bacteria in the cosmetics, and are simple and convenient to operate, high in accuracy and excellent in repeatability.

The invention relates to a primer probe combination and a fluorescence quantitative polymerase chain reaction (PCR) kit for simultaneous detection of three types of cryptococcus, belonging to the technical field of in-vitro molecular detection of pathogenic microorganisms. The invention provides the primer probe combination for simultaneous detection of the three types of cryptococcus based on a fluorescence PCR method. The three types of cryptococcus comprise cryptococcus neoformans, cryptococcus gattii and cryptococcus laurentii; primers comprise an upstream primer and a downstream primer, wherein the nucleotide sequence of the upstream primer is shown in SEQ ID No.1, and the nucleotide sequence of the downstream primer is shown in SEQ ID No.2; a probe is a substance which is modified with a fluorophore at the 5'end and is modified with a fluorescence quenching group at the 3'end in a sequence shown in the SEQ ID No.3. The primer probe combination provided by the invention can realize the simultaneous detection of the cryptococcus neoformans, the cryptococcus gattii and the cryptococcus laurentii, and is high in detection specificity and high in sensitivity.

The compositions and methods described herein disclose the design, synthesis and testing of compounds that act as inhibitors of DHFR. The basic scaffold of these inhibitors includes a 2,4-diaminopyrimidine ring with a propargyl linker to another substituted aryl, bicyclo or heteroaryl ring. These DHFR inhibitors are potent and selective for many different pathogenic organisms, including the DHFR enzyme from bacteria such as Bacillus anthracis and methicillin-resistant Staphylococcus aureus, fungi such as Candida glabrata, Candida albicans and Cryptococcus neoformans and protozoa such as Cryptosporidium hominis and Toxoplasma gondii. These compounds and other similar compounds are also potent against the mammalian enzyme and may be useful as anti-cancer therapeutics.

The invention provides a gene chip and a kit for detecting invasive fungal pathogenic bacteria. The gene chip comprises a solid phase vector and an oligonucleotide probe fixed on the solid phase vector, wherein the probe contains DNA (Deoxyribose Nucleic Acid) sequences selected from 18S to 5.8S or 5.8S to 28S inside transcription regions (ITS) of rDNA and 5.8S rDNA of candida albicans, candida parapsilosis, candida tropicalis, candida kefyr, candida drusei, candida lusitaniae, candida glabrata, candida guilliermondii and cryptococcus neoformans as well as 5.8S rDNA of the nine fungus. The gene chip and the kit of the invention are utilized to detect nine kinds of common pathogenic bacteria, and have the advantages of simple and convenient operation, high accuracy and strong repeatability.

The invention discloses a 1, 5-benzodiazepine compound containing thiazolyl and ester and an application of the compound, and a structural formula of the compound is represented by a formula (I). The compound has a broader spectrum and higher activity for inhibiting funguses ad bacteria, and in-vitro antibacterial activity test result shows that the compound has a more obvious activity inhabiting effect and a higher killing effect on two types of funguses including cryptococcus neoformans clinical strains and standard strains as well as candida albicans, has a very high activity inhabiting effect and a very high killing effect on two types of bacteria including positive bacteria, namely staphylococcus aureus, as well as negative bacteria, namely escherichia coli, and can be taken as a candidate molecule and a lead compound for an antibacterial agent; and the structural formula of the compound is represented as the instruction shown.

The invention relates to the technical field of medicines, particularly to six triterpene glycosides antifungal compounds HolotoxinD-I separated from a sea cucumber. The chemical structural formula isas follows on the right. An in vitro anifungal experiment shows that the compounds have obvious inhibitory effect on Candida ablbicans SC5314, Cryptococcus neoformans BLS108, Candida tropicalis, Trichophyton rubrum, Mircrosporum gypeseum and fuming Aspergillus. The invention can provide leading compounds for developing novel antifungal drug, and has a significant value on exploiting and using marine medical resources in China.

The invention relates to a usage of an ocean fungal extract-active natural product B. According to the result of an in vitro research trial, the active natural product B has certain inhibitory effecton common clinical pathogenic fungi such as white tritirachium album limber, cryptococcus neoformans, trichophyton rubrum and aspergillus fumigatus and the like, is able to inordinately inhibit the growth of tumor cell lines such as liver cancer, breast cancer and lung cancer and the like, and is able to have stronger protective effect on pathological mechanism damages caused by rat multi-infarctcerebral ischemia damage and the like, thus being capable of obviously improving the learning and memory functions of dementia rat, and being applied to prepare dementia product having anti-angiogeniceffect. The invention provides a new pharmaceutical source for the curing of clinical antifungal, antitumor and anti-vascular dementia and directly related diseases thereof, having important value for developing and utilizing the pharmaceutical resource of our country.

The invention relates to the field of molecular biology detection, and more specifically to the detection of Candida albicans, Cryptococcus neoformans, and Pneumocystis jiroveci. The invention provides a composition for detecting the above-mentioned fungi; and at the same time also provides a kit containing the composition, a use of the composition, and a method for detecting and typing deep infection fungi. The composition of the invention can simultaneously detect the three fungi in one tube and perform typing by combining with a fluorescent probe method, and has the advantage that the costis low, the throughput is high, time-consuming is short, the operation is simple and convenient, and false positives caused by crossover between samples and environmental pollution are avoided. Further, the composition of the invention is adapted to a one-step method, the sensitivity and specificity are ensured while the detection time is saved and the detection efficiency is improved.

Provided herein are uses of genes for HOG, Ras and cAMP signal transduction pathways to treat fungal infection. To regulate the HOG pathway of Cryptococcus neoformans, roles of SSK1, TCO2, SSK2, PBS2, HOG1, ENA1 and NHA1 genes were investigated to find that a biosynthesis level of ergosterol is increased when these genes are inhibited. When the genes are inhibited, a large amount of ergosterol is distributed on a fungal cell membrane. Accordingly, since there are many working points of an ergosterol-binding antifungal agent, an efficiency of the ergosterol-binding antifungal agent can be considerably improved. To regulate the Ras and cAMP pathways of Cryptococcus neoformans, roles of RAS1, RAS2, CDC24, GPA1, CAC1, ACA1, PKA1, HSP12 and HSP122 genes were investigated to find that a sensitivity to a polyene- or azole-based drug is increased when these genes are inhibited. Therefore, an antifungal pharmaceutical composition including an inhibitor against the gene or protein encoded by the same can be used as an excellent combined antifungal agent which can reduce a conventional amount of an antifungal agent used and increase an efficiency.

Provided herein are uses of genes for HOG, Ras and cAMP signal transduction pathways to treat fungal infection. To regulate the HOG pathway of Cryptococcus neoformans, roles of SSK1, TCO2, SSK2, PBS2, HOG1, ENA1 and NHA1 genes were investigated to find that a biosynthesis level of ergosterol is increased when these genes are inhibited. When the genes are inhibited, a large amount of ergosterol is distributed on a fungal cell membrane. Accordingly, since there are many working points of an ergosterol-binding antifungal agent, an efficiency of the ergosterol-binding antifungal agent can be considerably improved. To regulate the Ras and cAMP pathways of Cryptococcus neoformans, roles of RAS1, RAS2, CDC24, GPA1, CAC1, ACA1, PKA1, HSP12 and HSP122 genes were investigated to find that a sensitivity to a polyene- or azole-based drug is increased when these genes are inhibited. Therefore, an antifungal pharmaceutical composition including an inhibitor against the gene or protein encoded by the same can be used as an excellent combined antifungal agent which can reduce a conventional amount of an antifungal agent used and increase an efficiency.

The invention discloses an application of ovateleaf knotweed rhizomes used for preparing antifungal drugs and a synergist thereof, belongs to the technical field of medicine. In vitro cell experimentsshow that ovateleaf knotweed rhizomes have different degrees of antifungal and even fungicidal effects against drug-resistant Candida albicans 103, susceptible Candida albicans SC5314, Cryptococcus neoformans 32609, natural drug-resistant Candida krusei ATCC 2340, Candida parapsilosis 22019, natural drug-resistant Candida glabrata ATCC 2281 and drug-resistant Candida tropicalis, so that the ovateleaf knotweed rhizomes can be used as an antifungal drug and a synergist thereof. The invention opens up a new use for ovateleaf knotweed rhizomes, uses the ovateleaf knotweed rhizomes for preparing antifungal drugs, and provides a new drug candidate for the treatment of fungal infections.

The invention belongs to the field of pharmaceutical preparation, and in particular relates to application of Ponatinib in preparing drugs for treating fungal infections. Ponatinib has a therapeutic effect on fungal infections, especially when used in combination with fluonazole, not only has a good fungistatic effect, but also achieves a fungicidal effect against fungal infections; and furthermore, Ponatinib has a broad-spectrum antifungal effect, and has good killing effects on fluconazole-resistant Candida albicans strains, Cryptococcus neoformans and Saccharomyces cerevisiae. According tothe present invention, a gene PDR5 and a gene PMA1 are found to be drug targets of Ponatinib for antifungal infection effect, and a new development direction and action mechanism for the treatment offungal infections and research and development of therapeutic drugs are provided.