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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
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Official URL: http://dx.doi.org/10.1371/journal.pone.0015693
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 | ||||
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| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection Faculty of Medicine > Warwick Medical School |
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| 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: |
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| 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 | ||||
| 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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