Steps Toward Broad-spectrum Therapeutics: Discovering Virulence-associated Genes Present in Diverse Human Pathogens

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2009 Oct 31

PMID 19874620

Citations 9

Authors

Chris J Stubben

Melanie L Duffield

Ian A Cooper

Donna C Ford

Jason D Gans

Andrey V Karlyshev

Bryan Lingard

Petra C F Oyston

Anna de Rochefort

Jian Song

Brendan W Wren

Rick W Titball

Murray Wolinsky

Affiliations

Soon will be listed here.

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.

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