The serum resistome of a globally disseminated multidrug resistant uropathogenic Escherichia coli clone

Phan, Minh-Duy, Peters, Kate M., Sarkar, Sohinee, Lukowski, Samuel W., Allsopp, Luke P., Moriel, Danilo Gomes, Achard, Maud E. S., Totsika, Makrina, Marshall, Vikki M., Upton, Mathew, Beatson, Scott A. and Schembri, Mark A. (2013) The serum resistome of a globally disseminated multidrug resistant uropathogenic Escherichia coli clone. PloS Genetics, 9 10: e1003834.1-e1003834.18. doi:10.1371/journal.pgen.1003834


Author Phan, Minh-Duy
Peters, Kate M.
Sarkar, Sohinee
Lukowski, Samuel W.
Allsopp, Luke P.
Moriel, Danilo Gomes
Achard, Maud E. S.
Totsika, Makrina
Marshall, Vikki M.
Upton, Mathew
Beatson, Scott A.
Schembri, Mark A.
Title The serum resistome of a globally disseminated multidrug resistant uropathogenic Escherichia coli clone
Formatted title
The serum resistome of a globally disseminated multidrug resistant uropathogenic Escherichia coli clone
Journal name PloS Genetics   Check publisher's open access policy
ISSN 1553-7404
Publication date 2013-10-03
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1003834
Open Access Status DOI
Volume 9
Issue 10
Start page e1003834.1
End page e1003834.18
Total pages 18
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Escherichia coli ST131 is a globally disseminated, multidrug resistant clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with antibiotic resistance; however, this phenotype alone is unlikely to explain its dominance amongst multidrug resistant uropathogens circulating worldwide in hospitals and the community. Thus, a greater understanding of the molecular mechanisms that underpin the fitness of E. coli ST131 is required. In this study, we employed hyper-saturated transposon mutagenesis in combination with multiplexed transposon directed insertion-site sequencing to define the essential genes required for in vitro growth and the serum resistome (i.e. genes required for resistance to human serum) of E. coli EC958, a representative of the predominant E. coli ST131 clonal lineage. We identified 315 essential genes in E. coli EC958, 231 (73%) of which were also essential in E. coli K-12. The serum resistome comprised 56 genes, the majority of which encode membrane proteins or factors involved in lipopolysaccharide (LPS) biosynthesis. Targeted mutagenesis confirmed a role in serum resistance for 46 (82%) of these genes. The murein lipoprotein Lpp, along with two lipid A-core biosynthesis enzymes WaaP and WaaG, were most strongly associated with serum resistance. While LPS was the main resistance mechanism defined for E. coli EC958 in serum, the enterobacterial common antigen and colanic acid also impacted on this phenotype. Our analysis also identified a novel function for two genes, hyxA and hyxR, as minor regulators of O-antigen chain length. This study offers novel insight into the genetic make-up of E. coli ST131, and provides a framework for future research on E. coli and other Gram-negative pathogens to define their essential gene repertoire and to dissect the molecular mechanisms that enable them to survive in the bloodstream and cause disease.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
School of Chemistry and Molecular Biosciences
 
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Citation counts: TR Web of Science Citation Count  Cited 38 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 11 Oct 2013, 20:56:18 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences