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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 ; Gomes Moriel, Danilo ; Achard, Maud E S ; Totsika, Makrina ; Marshall, Vikki M ; Upton, Mathew ; Beatson, Scott A ; Schembri, Mark A Richardson, Paul M.

PLoS genetics, 2013-10, Vol.9 (10), p.e1003834 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
The serum resistome of a globally disseminated multidrug resistant uropathogenic Escherichia coli clone
Autor: Phan, Minh-Duy ; Peters, Kate M ; Sarkar, Sohinee ; Lukowski, Samuel W ; Allsopp, Luke P ; Gomes Moriel, Danilo ; Achard, Maud E S ; Totsika, Makrina ; Marshall, Vikki M ; Upton, Mathew ; Beatson, Scott A ; Schembri, Mark A
Richardson, Paul M.
Assuntos: Bacterial genetics ; beta-Lactamases - genetics ; Biosynthesis ; Blood - microbiology ; Cloning ; Drug resistance in microorganisms ; Drug Resistance, Multiple, Bacterial - genetics ; E coli ; Escherichia coli ; Gene Expression Regulation, Bacterial ; Genes ; Genetic aspects ; Genomes ; Humans ; Infections ; Microbiology ; Molecular Epidemiology ; Mutagenesis ; Physiological aspects ; Proteins ; Studies ; Urinary Tract Infections - microbiology ; Urogenital system ; Uropathogenic Escherichia coli - genetics ; Uropathogenic Escherichia coli - pathogenicity ; Virulence - drug effects ; Virulence - genetics
É parte de: PLoS genetics, 2013-10, Vol.9 (10), p.e1003834
Notas: The authors have declared that no competing interests exist.
Conceived and designed the experiments: MDP SS MT SAB MAS. Performed the experiments: MDP KMP SS SWL LPA MESA VMM. Analyzed the data: MDP DGM SAB MAS. Contributed reagents/materials/analysis tools: VMM MU SAB. Wrote the paper: MDP SS DGM MT MU SAB MAS.
Current address: Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
Descrição: 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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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 ; Gomes Moriel, Danilo ; Achard, Maud E S ; Totsika, Makrina ; Marshall, Vikki M ; Upton, Mathew ; Beatson, Scott A ; Schembri, Mark A Richardson, Paul M.

United States: Public Library of Science

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