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Genome-wide analysis reveals loci encoding anti-macrophage factors in the human pathogen burkholderia pseudomallei K96243

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Dowling, Andrea J., Wilkinson, Paul A., Holden, Matthew T. G., Quail, Michael A., Bentley, Stephen D., Reger, Julia, Waterfield, Nicholas R., Titball, Richard W. and ffrench-Constant, Richard H. (2010) Genome-wide analysis reveals loci encoding anti-macrophage factors in the human pathogen burkholderia pseudomallei K96243. PLoS One, Volume 5 (Number 12). Article number e15693. doi:10.1371/journal.pone.0015693 ISSN 1932-6203.

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Official URL: http://dx.doi.org/10.1371/journal.pone.0015693

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Abstract

Burkholderia pseudomallei is an important human pathogen whose infection biology is still poorly understood. The bacterium is endemic to tropical regions, including South East Asia and Northern Australia, where it causes melioidosis, a serious disease associated with both high mortality and antibiotic resistance. B. pseudomallei is a Gram-negative facultative intracellular pathogen that is able to replicate in macrophages. However despite the critical nature of its interaction with macrophages, few anti-macrophage factors have been characterized to date. Here we perform a genome-wide gain of function screen of B. pseudomallei strain K96243 to identify loci encoding factors with anti-macrophage activity. We identify a total of 113 such loci scattered across both chromosomes, with positive gene clusters encoding transporters and secretion systems, enzymes/toxins, secondary metabolite, biofilm, adhesion and signal response related factors. Further phenotypic analysis of four of these regions shows that the encoded factors cause striking cellular phenotypes relevant to infection biology, including apoptosis, formation of actin ‘tails’ and multi-nucleation within treated macrophages. The detailed analysis of the remaining host of loci will facilitate genetic dissection of the interaction of this important pathogen with host macrophages and thus further elucidate this critical part of its infection cycle.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Bacterial genetics, Melioidosis, Pseudomonas infections, Bacterial diseases, Macrophages
Journal or Publication Title: PLoS One
Publisher: Public Library of Science
ISSN: 1932-6203
Official Date: 2010
Dates:
DateEvent
2010Published
Volume: Volume 5
Number: Number 12
Page Range: Article number e15693
DOI: 10.1371/journal.pone.0015693
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 26 December 2015
Date of first compliant Open Access: 26 December 2015
Funder: Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Seventh Framework Programme (European Commission) (FP7)
Grant number: BB/E021182/1 (BBSRC) ; 223328 (GAMEXP) (FP7)

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