Steps toward broad-spectrum therapeutics: discovering virulence-associated genes present in diverse human pathogens Export

@article{citeulike:6040601, abstract = {BACKGROUND:New and improved antimicrobial countermeasures are urgently needed to counteract increased resistance to existing antimicrobial treatments and to combat currently untreatable or new emerging infectious diseases. We demonstrate that computational comparative genomics, together with experimental screening, can identify potential generic (i.e., conserved across multiple pathogen species) and novel virulence-associated genes that may serve as targets for broad-spectrum countermeasures.RESULTS:Using phylogenetic profiles of protein clusters from completed microbial genome sequences, we identified seventeen protein candidates that are common to diverse human pathogens and absent or uncommon in non-pathogens. Mutants of 13 of these candidates were successfully generated in Yersinia pseudotuberculosis and the potential role of the proteins in virulence was assayed in an animal model. Six candidate proteins are suggested to be involved in the virulence of Y. pseudotuberculosis, none of which have previously been implicated in the virulence of Y. pseudotuberculosis and three have no record of involvement in the virulence of any bacteria.CONCLUSION:This work demonstrates a strategy for the identification of potential virulence factors that are conserved across a number of human pathogenic bacterial species, confirming the usefulness of this tool.}, author = {Stubben, Chris and Duffield, Melanie and Cooper, Ian and Ford, Donna and Gans, Jason and Karlyshev, Andrey and Lingard, Bryan and Oyston, Petra and de Rochefort, Anna and Song, Jian and Wren, Brendan and Titball, Rick and Wolinsky, Murray}, citeulike-article-id = {6040601}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1471-2164-10-501}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19874620}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19874620}, doi = {10.1186/1471-2164-10-501}, issn = {1471-2164}, journal = {BMC Genomics}, keywords = {candidate\_genes, genome\_features, genomeproperties, phylogenetic\_profiles, virulence}, number = {1}, pages = {501+}, posted-at = {2009-10-30 06:55:03}, priority = {2}, title = {Steps toward broad-spectrum therapeutics: discovering virulence-associated genes present in diverse human pathogens}, url = {http://dx.doi.org/10.1186/1471-2164-10-501}, volume = {10}, year = {2009} }

TY - JOUR ID - citeulike:6040601 L3 - citeulike-article-id:6040601 N2 - BACKGROUND:New and improved antimicrobial countermeasures are urgently needed to counteract increased resistance to existing antimicrobial treatments and to combat currently untreatable or new emerging infectious diseases. We demonstrate that computational comparative genomics, together with experimental screening, can identify potential generic (i.e., conserved across multiple pathogen species) and novel virulence-associated genes that may serve as targets for broad-spectrum countermeasures.RESULTS:Using phylogenetic profiles of protein clusters from completed microbial genome sequences, we identified seventeen protein candidates that are common to diverse human pathogens and absent or uncommon in non-pathogens. Mutants of 13 of these candidates were successfully generated in Yersinia pseudotuberculosis and the potential role of the proteins in virulence was assayed in an animal model. Six candidate proteins are suggested to be involved in the virulence of Y. pseudotuberculosis, none of which have previously been implicated in the virulence of Y. pseudotuberculosis and three have no record of involvement in the virulence of any bacteria.CONCLUSION:This work demonstrates a strategy for the identification of potential virulence factors that are conserved across a number of human pathogenic bacterial species, confirming the usefulness of this tool. IS - 1 JF - BMC Genomics SN - 1471-2164 TI - Steps toward broad-spectrum therapeutics: discovering virulence-associated genes present in diverse human pathogens VL - 10 SP - 501 KW - candidate_genes KW - genome_features KW - genomeproperties KW - phylogenetic_profiles KW - virulence AU - Stubben, Chris AU - Duffield, Melanie AU - Cooper, Ian AU - Ford, Donna AU - Gans, Jason AU - Karlyshev, Andrey AU - Lingard, Bryan AU - Oyston, Petra AU - de Rochefort, Anna AU - Song, Jian AU - Wren, Brendan AU - Titball, Rick AU - Wolinsky, Murray PY - 2009/// UR - http://dx.doi.org/10.1186/1471-2164-10-501 ER -