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- Title
Development of carbapenem resistance in Pseudomonas aeruginosa is associated with OprD polymorphisms, particularly the amino acid substitution at codon 170.
- Authors
Jwu-Ching Shu; An-Jing Kuo; Lin-Hui Su; Tsui-Ping Liu; Ming-Hsun Lee; I-Ning Su; Tsu-Lan Wu; Shu, Jwu-Ching; Kuo, An-Jing; Su, Lin-Hui; Liu, Tsui-Ping; Lee, Ming-Hsun; Su, I-Ning; Wu, Tsu-Lan
- Abstract
<bold>Objectives: </bold>Pan-susceptible Pseudomonas aeruginosa (PSPA) clinical isolates carrying an OprD with loop 7 shortening (the group-1A allele) were found to rapidly develop carbapenem resistance under continuous selection pressure. We further studied whether OprD polymorphisms are associated with the potential to develop carbapenem resistance.<bold>Methods: </bold>OprD amino acid sequences of 126 PSPA clinical isolates were analysed to determine their STs using P. aeruginosa strain PAO1 as the control strain. Site-directed mutagenesis was performed in PAO1 to generate polymorphisms of interest. A disc diffusion method was used to select carbapenem-resistant variants from the mutant strains. Expression levels of oprD were determined by quantitative RT-PCR. MICs of carbapenems were determined by Etest.<bold>Results: </bold>Forty-eight (38.1%) of the tested isolates carried the group-1A allele. Another two major STs, C1 and C2, both of which harboured an F170L polymorphism, were found in 21 (16.7%) and 39 (31.0%) isolates, respectively. The PAO1 type was also found in 14 (11.1%) isolates. Under continuous selective pressure, isolates of most STs developed carbapenem resistance at different numbers of passaging events; only those belonging to the PAO1 type remained susceptible. However, PAO1 mutants carrying either the oprD group-1A allele or the OprD-F170L polymorphism were able to develop carbapenem resistance. Reduced oprD expression triggered by continuous imipenem challenge was found in PAO1 mutants, but not in the PAO1 WT strain.<bold>Conclusions: </bold>OprD polymorphisms, particularly the F170L substitution and the specific shortening in loop 7, appear to determine the potential for P. aeruginosa to develop carbapenem resistance.
- Subjects
PSEUDOMONAS aeruginosa; CARBAPENEMS; DRUG resistance in bacteria; GENETIC polymorphisms; AMINO acid sequence; GENETIC code; SITE-specific mutagenesis; THERAPEUTICS; BACTERIA; ALLELES; AMINO acids; ANTIBIOTICS; BACTERIAL proteins; DRUG resistance in microorganisms; MEMBRANE proteins; MICROBIAL sensitivity tests; GENETIC mutation; PSEUDOMONAS; PSEUDOMONAS diseases; PHARMACODYNAMICS
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2017, Vol 72, Issue 9, p2489
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkx158