Mechanisms of Heteroresistance and Resistance to Imipenem in Pseudomonas aeruginosa

Heteroresistance is a phenomenon that occurs in all bacteria and can cause treatment failure. Yet, the exact mechanisms responsible for heteroresistance still remain unknown. The following study investigated the mechanisms of imipenem-heteroresistance and -resistance in clinical isolates from Wenzho...

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Published in:Infection and drug resistance 2020-01, Vol.13, p.1419-1428
Main Authors: Xu, Ye, Zheng, Xiangkuo, Zeng, Weiliang, Chen, Tao, Liao, Wenli, Qian, Jiao, Lin, Jie, Zhou, Cui, Tian, Xuebin, Cao, Jianming, Zhou, Tieli
Format: Article
Language:English
Subjects:
Antibiotics
Antimicrobial agents
Bacteria
Beta lactamases
Biofilms
Clinical isolates
Deoxyribonucleic acid
DNA
Gene amplification
Gene expression
Genotype & phenotype
heteroresistance
Imipenem
Meropenem
molecular mechanism
Mutation
Nosocomial infections
oprd
Original Research
Polymerase chain reaction
Proteins
Pseudomonas aeruginosa
resistance
Strains (organisms)
Subpopulations
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Summary:Heteroresistance is a phenomenon that occurs in all bacteria and can cause treatment failure. Yet, the exact mechanisms responsible for heteroresistance still remain unknown. The following study investigated the mechanisms of imipenem-heteroresistance and -resistance in clinical isolates from Wenzhou, China. Imipenem resistance was detected by the agar dilution method; heteroresistance was determined by population analysis profiles. Biofilm formation assay and modified carbapenem inactivation methods were also performed. Polymerase chain reaction (PCR) was conducted to detect , and quantitative real-time PCR was used to determine expression levels of and four efflux pump coding genes ( and ). Six imipenem-heteroresistant and -resistant isolates were selected respectively. Deficient was detected in all resistant isolates and two heteroresistant isolates. No strains produced carbapenemases. Expression levels of were down-regulated in heteroresistant isolates. Transcription levels of the and were significantly increased in all heterogeneous subpopulations compared with their respective native ones. Compared with the susceptible group, increased mean relative expression levels of and or the decreased mean relative expression levels of were observed in the resistant group ( < 0.05), whereas transcription levels of the and remained unchanged. Down-regulation of contributed to the resistance and heteroresistance of imipenem in our clinical isolates. In addition, the marginal up-regulation of efflux systems may indirectly affect imipenem resistance. Contrarily, defective was less common in our experimental heteroresistant strains than resistant strains.
ISSN:1178-6973
1178-6973
DOI:10.2147/IDR.S249475