Host Factors and Portal of Entry Outweigh Bacterial Determinants To Predict the Severity of Escherichia coli Bacteremia

Lefort, A.; Panhard, Xavière; Clermont, Olivier; Woerther, Paul‐Louis; Branger, Catherine; Fantin, Bruno; Wolff, Michel; Denamur, Erick

doi:10.1128/jcm.01902-10

Cited by 127 publications

(166 citation statements)

References 52 publications

(64 reference statements)

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“…Comparison with the virulence factor database (https://cge.cbs .dtu.dk/services/VirulenceFinder/) and with the study of Lefort et al (13) showed that sat, iha, iss, sfa, irp2, fyuA, and iucC genes were harbored by both isolates. Sat is a secreted autotransporter toxin that alters the structural and functional components of intercellular junctions (14), iha is an iron-regulated gene homologue adhesin that augments adherence to uroepithelial cells (15), sfa codes for the S fimbrial adhesin (13), iss is a serum survival gene associated with a 20-fold increase in complement resistance (16), and irp2, fyuA, and iucC genes belong to the iron capture systems (13).…”

Section: Resultsmentioning

confidence: 99%

Structural Alteration of OmpR as a Source of Ertapenem Resistance in a CTX-M-15-Producing Escherichia coli O25b:H4 Sequence Type 131 Clinical Isolate

Dupont

Choinier

Roche

et al. 2017

Antimicrob Agents Chemother

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In this study, an ertapenem-nonsusceptible Escherichia coli isolate was investigated to determine the genetic basis for its carbapenem resistance phenotype. This clinical strain was recovered from a patient that received, 1 year previously, ertapenem to treat a cholangitis due to a carbapenem-susceptible extendedspectrum-␤-lactamase (ESBL)-producing E. coli isolate. Whole-genome sequencing of these strains was performed using Illumina and single-molecule real-time sequencing technologies. It revealed that they belonged to the ST131 clonal group, had the predicted O25b:H4 serotype, and produced the CTX-M-15 and TEM-1 ␤-lactamases. One nucleotide substitution was identified between these strains. It affected the ompR gene, which codes for a regulatory protein involved in the control of OmpC/ OmpF porin expression, creating a Gly-63-Val substitution. The role of OmpR alteration was confirmed by a complementation experiment that fully restored the susceptibility to ertapenem of the clinical isolate. A modeling study showed that the Gly-63-Val change displaced the histidine-kinase phosphorylation site. SDS-PAGE analysis revealed that the ertapenem-nonsusceptible E. coli strain had a decreased expression of OmpC/OmpF porins. No significant defect in the growth rate or in the resistance to Dictyostelium discoideum amoeba phagocytosis was found in the ertapenem-nonsusceptible E. coli isolate compared to its susceptible parental strain. Our report demonstrates for the first time that ertapenem resistance may emerge clinically from ESBL-producing E. coli due to mutations that modulate the OmpR activity.KEYWORDS OmpR, ST131, avibactam, carbapenem, envZ, ESBL, temocillin C arbapenems are broad-spectrum antibiotics usually reserved for severe lifethreatening infections. Some enterobacterial isolates have developed carbapenem resistance, which resulted in limited options for the treatment of infections caused by these organisms. Except for the members of the Proteeae tribe, carbapenem resistance in Enterobacteriaceae is almost always attributable to the production of ␤-lactamases, which can be distinguished according to their carbapenemase activity. True carbapenemases (e.g., KPC, OXA-48, and metallo-␤-lactamases [MBLs]) confer per se resistance to carbapenems, whereas extended-spectrum ␤-lactamases (ESBLs) and AmpC-type enzymes require an additional mechanism of resistance, such as decrease in the uptake

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Section: Resultsmentioning

confidence: 99%

Structural Alteration of OmpR as a Source of Ertapenem Resistance in a CTX-M-15-Producing Escherichia coli O25b:H4 Sequence Type 131 Clinical Isolate

Dupont

Choinier

Roche

et al. 2017

Antimicrob Agents Chemother

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“…VAP B2 phylogroup isolates were further characterized by presence of 11 additional VF [20], PCR O-typing [23], and B2-subgrouping [24].…”

Section: E Coli Isolates [See Electronic Supplementary Materials (Esm)]mentioning

confidence: 99%

“…Multiplex PCR was used to detect genes encoding for seven frequently encountered extraintestinal VF, which belong to the main classes of VF (adhesin, toxin, and iron capture system) (see ESM Table 1) [20]. The VF score was defined as the number of VF present divided by the number of VF tested for each isolate.…”

Section: E Coli Isolates [See Electronic Supplementary Materials (Esm)]mentioning

confidence: 99%

Pathophysiology of Escherichia coli ventilator-associated pneumonia: implication of highly virulent extraintestinal pathogenic strains

et al. 2012

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“…Lefort et al 9 reported that host driven risk factors and mode of bacterial entry were more important determinants of severity of sepsis then VFs. This COLI-BAFI study examined more than 1000 episodes of bacteremia from 15 centers and correlated severity of these episodes with bacterial determinants.…”

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confidence: 99%

The importance of the “V”-Factor:Escherichia colibacteremia and sepsis

Murphy¹,

Thumbikat²

2015

Virulence

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Host Factors and Portal of Entry Outweigh Bacterial Determinants To Predict the Severity of Escherichia coli Bacteremia

Cited by 127 publications

References 52 publications

Structural Alteration of OmpR as a Source of Ertapenem Resistance in a CTX-M-15-Producing Escherichia coli O25b:H4 Sequence Type 131 Clinical Isolate

Structural Alteration of OmpR as a Source of Ertapenem Resistance in a CTX-M-15-Producing Escherichia coli O25b:H4 Sequence Type 131 Clinical Isolate

Pathophysiology of Escherichia coli ventilator-associated pneumonia: implication of highly virulent extraintestinal pathogenic strains

The importance of the “V”-Factor:Escherichia colibacteremia and sepsis

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