Insights into a multidrug resistant Escherichia coli pathogen of the globally disseminated ST131 lineage: Genome analysis and virulence mechanisms

Totsika, M; Beatson, SA; Sarkar, S; Phan, MD; Petty, NK; Bachmann, N; Szubert, M; Sidjabat, HE; Paterson, DL; Upton, M; Schembri, MA

Insights into a multidrug resistant Escherichia coli pathogen of the globally disseminated ST131 lineage: Genome analysis and virulence mechanisms

Totsika, M Beatson, SA Sarkar, S Phan, MD Petty, NK

Bachmann, N Szubert, M Sidjabat, HE Paterson, DL Upton, M Schembri, MA

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Publication Type:: Journal Article
Citation:: PLoS ONE, 2011, 6 (10)
Issue Date:: 2011-11-02

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Field	Value	Language
dc.contributor.author	Totsika, M	en_US
dc.contributor.author	Beatson, SA	en_US
dc.contributor.author	Sarkar, S	en_US
dc.contributor.author	Phan, MD	en_US
dc.contributor.author	Petty, NK https://orcid.org/0000-0001-6528-9886	en_US
dc.contributor.author	Bachmann, N	en_US
dc.contributor.author	Szubert, M	en_US
dc.contributor.author	Sidjabat, HE	en_US
dc.contributor.author	Paterson, DL	en_US
dc.contributor.author	Upton, M	en_US
dc.contributor.author	Schembri, MA	en_US
dc.date.available	2011-09-29	en_US
dc.date.issued	2011-11-02	en_US
dc.identifier.citation	PLoS ONE, 2011, 6 (10)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/27797
dc.description.abstract	Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI. © 2011 Totsika et al.	en_US
dc.relation.ispartof	PLoS ONE	en_US
dc.relation.isbasedon	10.1371/journal.pone.0026578	en_US
dc.subject.classification	General Science & Technology	en_US
dc.subject.mesh	Fimbriae, Bacterial	en_US
dc.subject.mesh	Urine	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Escherichia coli	en_US
dc.subject.mesh	Escherichia coli Infections	en_US
dc.subject.mesh	Disease Models, Animal	en_US
dc.subject.mesh	Virulence Factors	en_US
dc.subject.mesh	Anti-Bacterial Agents	en_US
dc.subject.mesh	Colony Count, Microbial	en_US
dc.subject.mesh	Mutagenesis, Insertional	en_US
dc.subject.mesh	Sequence Analysis, DNA	en_US
dc.subject.mesh	Phylogeny	en_US
dc.subject.mesh	Drug Resistance, Multiple, Bacterial	en_US
dc.subject.mesh	Virulence	en_US
dc.subject.mesh	Base Sequence	en_US
dc.subject.mesh	Mutation	en_US
dc.subject.mesh	Genes, Bacterial	en_US
dc.subject.mesh	Genome, Bacterial	en_US
dc.subject.mesh	Operon	en_US
dc.subject.mesh	Plasmids	en_US
dc.subject.mesh	Internationality	en_US
dc.subject.mesh	Australia	en_US
dc.subject.mesh	United Kingdom	en_US
dc.subject.mesh	Urinary Bladder	en_US
dc.title	Insights into a multidrug resistant Escherichia coli pathogen of the globally disseminated ST131 lineage: Genome analysis and virulence mechanisms	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.citation.volume	6	en_US
utslib.for	0605 Microbiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	closed_access
pubs.issue	10	en_US
pubs.publication-status	Published	en_US
pubs.volume	6	en_US

Abstract:

Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI. © 2011 Totsika et al.

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http://hdl.handle.net/10453/27797