Unknown

Dataset Information

0

Acquisition of Carbapenem Resistance by Plasmid-Encoded-AmpC-Expressing Escherichia coli.


ABSTRACT: Although AmpC ?-lactamases can barely degrade carbapenems, if at all, they can sequester them and prevent them from reaching their targets. Thus, carbapenem resistance in Escherichia coli and other Enterobacteriaceae can result from AmpC production and simultaneous reduction of antibiotic influx into the periplasm by mutations in the porin genes. Here we investigated the route and genetic mechanisms of acquisition of carbapenem resistance in a clinical E. coli isolate carrying blaCMY-2 on a plasmid by selecting for mutants that are resistant to increasing concentrations of meropenem. In the first step, the expression of OmpC, the only porin produced in the strain under laboratory conditions, was lost, leading to reduced susceptibility to meropenem. In the second step, the expression of the CMY-2 ?-lactamase was upregulated, leading to resistance to meropenem. The loss of OmpC was due to the insertion of an IS1 element into the ompC gene or to frameshift mutations and premature stop codons in this gene. The blaCMY-2 gene was found to be located on an IncI? plasmid, and overproduction of the CMY-2 enzyme resulted from an increased plasmid copy number due to a nucleotide substitution in the inc gene. The clinical relevance of these genetic mechanisms became evident from the analysis of previously isolated carbapenem-resistant clinical isolates, which appeared to carry similar mutations.

SUBMITTER: van Boxtel R 

PROVIDER: S-EPMC5192137 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Acquisition of Carbapenem Resistance by Plasmid-Encoded-AmpC-Expressing Escherichia coli.

van Boxtel Ria R   Wattel Agnes A AA   Arenas Jesús J   Goessens Wil H F WH   Tommassen Jan J  

Antimicrobial agents and chemotherapy 20161227 1


Although AmpC β-lactamases can barely degrade carbapenems, if at all, they can sequester them and prevent them from reaching their targets. Thus, carbapenem resistance in Escherichia coli and other Enterobacteriaceae can result from AmpC production and simultaneous reduction of antibiotic influx into the periplasm by mutations in the porin genes. Here we investigated the route and genetic mechanisms of acquisition of carbapenem resistance in a clinical E. coli isolate carrying bla<sub>CMY-2</sub  ...[more]

Similar Datasets

| S-EPMC514751 | biostudies-literature
| S-EPMC7179281 | biostudies-literature
| S-EPMC3719783 | biostudies-literature
| S-EPMC4806949 | biostudies-literature
| S-EPMC6707864 | biostudies-literature
| S-EPMC90164 | biostudies-literature
| S-EPMC6581752 | biostudies-literature
| S-EPMC7734786 | biostudies-literature
| S-EPMC187336 | biostudies-literature
| S-EPMC2551761 | biostudies-literature