Dataset Information

Novel and unique domains in aminoacyl-tRNA synthetases from human fungal pathogens Aspergillus niger, Candida albicans and Cryptococcus neoformans.

ABSTRACT: BACKGROUND: Some species of fungi can cause serious human diseases, particularly to immuno-compromised individuals. Opportunistic fungal infections are a leading cause of mortality, and present an emerging challenge that requires development of new and effective therapeutics. Aminoacyl-tRNA synthetases (aaRSs) are indispensable components of cellular protein translation machinery and can be targeted for discovery of novel anti-fungal agents. RESULTS: Validation of aaRSs as potential drug targets in pathogenic microbes prompted us to investigate the genomic distribution of aaRSs within three fungi that infect humans - A. niger, C. albicans and C. neoformans. Hidden Markov Models were built for aaRSs and related proteins to search for homologues in these fungal genomes. Here, we provide a detailed and comprehensive annotation for 3 fungal genome aaRSs and their associated proteins. We delineate predicted localizations, subdomain architectures and prevalence of unusual motifs within these aaRSs. Several fungal aaRSs have unique domain appendages of unknown function e.g. A. niger AsxRS and C. neoformans TyrRS have additional domains that are absent from human homologs. CONCLUSIONS: Detailed comparisons of fungal aaRSs with human homologs suggest key differences that could be exploited for specific drug targeting. Our cataloging and structural analyses provide a comprehensive foundation for experimentally dissecting fungal aaRSs that may enable development of new anti-fungal agents.

SUBMITTER: Datt M

PROVIDER: S-EPMC4301749 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Novel and unique domains in aminoacyl-tRNA synthetases from human fungal pathogens Aspergillus niger, Candida albicans and Cryptococcus neoformans.

Datt Manish M Sharma Amit A

BMC genomics 20141205

<h4>Background</h4>Some species of fungi can cause serious human diseases, particularly to immuno-compromised individuals. Opportunistic fungal infections are a leading cause of mortality, and present an emerging challenge that requires development of new and effective therapeutics. Aminoacyl-tRNA synthetases (aaRSs) are indispensable components of cellular protein translation machinery and can be targeted for discovery of novel anti-fungal agents.<h4>Results</h4>Validation of aaRSs as potential ...[more]

PMID: 25479903

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Project description:Bacteria interact with each other in nature and often compete for limited nutrient and space resources. However, it is largely unknown whether and how bacteria also interact with human fungal pathogens naturally found in the environment. Here, we identified a soil bacterium, Bacillus safensis, which potently blocked several key Cryptococcus neoformans virulence factors, including formation of the antioxidant pigment melanin and production of the antiphagocytic polysaccharide capsule. The bacterium also inhibited de novo cryptococcal biofilm formation but had only modest inhibitory effects on already formed biofilms or planktonic cell growth. The inhibition of fungal melanization was dependent on direct cell contact and live bacteria. B. safensis also had anti-virulence factor activity against another major human-associated fungal pathogen, Candida albicans Specifically, dual-species interaction studies revealed that the bacterium strongly inhibited C. albicans filamentation and biofilm formation. In particular, B. safensis physically attached to and degraded candidal filaments. Through genetic and phenotypic analyses, we demonstrated that bacterial chitinase activity against fungal cell wall chitin is a factor contributing to the antipathogen effect of B. safensisIMPORTANCE Pathogenic fungi are estimated to contribute to as many human deaths as tuberculosis or malaria. Two of the most common fungal pathogens, Cryptococcus neoformans and Candida albicans, account for up to 1.4 million infections per year with very high mortality rates. Few antifungal drugs are available for treatment, and development of novel therapies is complicated by the need for pathogen-specific targets. Therefore, there is an urgent need to identify novel drug targets and new drugs. Pathogens use virulence factors during infection, and it has recently been proposed that targeting these factors instead of the pathogen itself may represent a new approach to develop antimicrobials. Here, we identified a soil bacterium that specifically blocked virulence factor production and biofilm formation by C. neoformans and C. albicans We demonstrate that the bacterial antipathogen mechanism is based in part on targeting the fungal cell wall, a structure not found in human cells.

Dataset Information

Novel and unique domains in aminoacyl-tRNA synthetases from human fungal pathogens Aspergillus niger, Candida albicans and Cryptococcus neoformans.

Publications

Novel and unique domains in aminoacyl-tRNA synthetases from human fungal pathogens Aspergillus niger, Candida albicans and Cryptococcus neoformans.

Similar Datasets

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