%0 Journal Article
%T Steps toward broad-spectrum therapeutics: discovering virulence-associated genes present in diverse human pathogens
%A Chris J Stubben
%A Melanie L Duffield
%A Ian A Cooper
%A Donna C Ford
%A Jason D Gans
%A Andrey V Karlyshev
%A Bryan Lingard
%A Petra CF Oyston
%A Anna de Rochefort
%A Jian Song
%A Brendan W Wren
%A Rick W Titball
%A Murray Wolinsky
%J BMC Genomics
%D 2009
%I BioMed Central
%R 10.1186/1471-2164-10-501
%X 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.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.Microbial disease is the major cause of human death and morbidity and for many infectious diseases, no preventive vaccines are available [1]. Where therapies do exist, escalation of resistance to antimicrobials hinders treatment of common bacterial infections and accentuates the need for new approaches [2,3]. Therefore, it is imperative to identify appropriate targets for medical countermeasures such as antimicrobial drugs or cross-protective vaccines active against several pathogenic strains or species. An alternative to "killing" bacteria, which exacerbates the selection of antimicrobial resistance, is to "disarm" bacteria by interfering with their capacity to be virulent, thus enabling the bacterium to survive and evoke an appropriate immune protection [4]. Targeting such virulence factors through the development of antivirulence (as opposed to antimicrobial) compounds has indicated that it is possible to target common virulence genes [5,6].Virulence is typically described as the damage a pathogen causes to the host during infection [7]. Gene products that contribute to virulence can therefore be described as virulence factors.
%U http://www.biomedcentral.com/1471-2164/10/501