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

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

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dc.contributor.author Stubben, Chris J. en_GB
dc.contributor.author Duffield, Melanie en_GB
dc.contributor.author Cooper, Ian A. en_GB
dc.contributor.author Ford, Donna C. en_GB
dc.contributor.author Gans, Jason D. en_GB
dc.contributor.author Karlyshev, Andrey V. en_GB
dc.contributor.author Lingard, Bryan en_GB
dc.contributor.author Oyston, Petra C. F. en_GB
dc.contributor.author de Rochefort, Anna en_GB
dc.contributor.author Song, Jian en_GB
dc.contributor.author Wren, Brendan W. en_GB
dc.contributor.author Titball, Richard W. en_GB
dc.contributor.author Wolinsky, Murray en_GB
dc.date.accessioned 2010-06-10T15:02:15Z en_GB
dc.date.accessioned 2011-01-25T11:47:15Z en_US
dc.date.accessioned 2013-03-20T14:50:41Z
dc.date.issued 2009 en_GB
dc.description.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. en_GB
dc.identifier.citation 10, article 501 en_GB
dc.identifier.doi 10.1186/1471-2164-10-501 en_GB
dc.identifier.uri http://hdl.handle.net/10036/104625 en_GB
dc.language.iso en en_GB
dc.publisher BioMed Central en_GB
dc.relation.url http://www.biomedcentral.com/1471-2164/10/501 en_GB
dc.relation.url http://dx.doi.org/10.1186/1471-2164-10-501 en_GB
dc.title Steps toward broad-spectrum therapeutics: discovering virulence-associated genes present in diverse human pathogens en_GB
dc.type Article en_GB
dc.date.available 2010-06-10T15:02:15Z en_GB
dc.date.available 2011-01-25T11:47:15Z en_US
dc.date.available 2013-03-20T14:50:41Z
dc.identifier.issn 1471-2164 en_GB
dc.description © 2009 Stubben et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_GB
dc.identifier.journal BMC Genomics en_GB


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