Characterization of mutations in Escherichia coli PBP2 leading to increased carbapenem MICs.
J Antimicrob Chemother
; 74(3): 571-576, 2019 03 01.
Article
in En
| MEDLINE
| ID: mdl-30496417
ABSTRACT
OBJECTIVES:
To examine the impact on carbapenem resistance of mutations in Escherichia coli PBP2 detected in clinical isolates showing increased MICs of imipenem, but not of meropenem.METHODS:
The mutations in the PBP2-encoding gene mrdA were introduced into E. coli DH5α using the helper plasmid pTKRED. ß-Lactam MICs were determined by broth microdilution and interpreted according to EUCAST. Mutants were screened for secondary mutations by WGS. To detect a possible fitness cost related to these mutations, the generation times of the mutants and E. coli DH5α were measured and their cell morphology was examined.RESULTS:
The 10 mutation patterns introduced into mrdA increased the MICs of imipenem and doripenem in all cases and of meropenem and mecillinam in some cases, but had no effect on ertapenem resistance. While no significant alteration of the generation time of the mutants could be detected, several mutants showed increased transverse diameters and thus altered cell morphology.CONCLUSIONS:
Here we describe mutation patterns in PBP2 that contribute to increased MICs of carbapenems for clinical isolates of E. coli. We show that different mutations affect carbapenem MICs differently and that the mutations do not impact generation time, although some mutations affect cell morphology.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carbapenems
/
Beta-Lactam Resistance
/
Escherichia coli Proteins
/
Penicillin-Binding Proteins
/
Escherichia coli
/
Anti-Bacterial Agents
/
Mutation
Language:
En
Journal:
J Antimicrob Chemother
Year:
2019
Document type:
Article
Affiliation country:
Germany