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Genomic variations in polymyxin-resistant Pseudomonas aeruginosa clinical isolates and their effects on polymyxin resistance

  • Bacterial, Fungal and Virus Molecular Biology - Research Paper
  • Published:
Brazilian Journal of Microbiology Aims and scope Submit manuscript

Abstract

Infection with P. aeruginosa, one of the most relevant opportunistic pathogens in hospital-acquired infections, can lead to high mortality due to its low antibiotic susceptibility to limited choices of antibiotics. Polymyxin as last-resort antibiotics is used in the treatment of systemic infections caused by multidrug-resistant P. aeruginosa strains, so studying the emergence of polymyxin-resistant was a must. The present study was designed to define genomic differences between paired polymyxin-susceptible and polymyxin-resistant P. aeruginosa strains and established polymyxin resistance mechanisms, and common chromosomal mutations that may confer polymyxin resistance were characterized. A total of 116 CRPA clinical isolates from patients were collected from three tertiary care hospitals in China during 2017–2021. Our study found that polymyxin B resistance represented 3.45% of the isolated carbapenem-resistant P. aeruginosa (CRPA). No polymyxin-resistant isolates were positive for mcr (1–8 and 10) gene and efflux mechanisms. Key genetic variations identified in polymyxin-resistant isolates involved missense mutations in parR, parS, pmrB, pmrA, and phoP. The waaL and PA5005 substitutions related to LPS synthesis were detected in the highest levels of resistant strain (R1). The missense mutations H398R in ParS (4/4), Y345H in PmrB (4/4), and L71R in PmrA (3/4) were the predominant. Results of the PCR further confirmed that mutation of pmrA, pmrB, and phoP individually or simultaneously did affect the expression level of resistant populations and can directly increase the expression of arnBCADTEF operon to contribute to polymyxin resistance. In addition, we reported 3 novel mutations in PA1945 (2129872_A < G, 2130270_A < C, 2130272_T < G) that may confer polymyxin resistance in P. aeruginosa. Our findings enriched the spectrum of chromosomal mutations, highlighted the complexity at the molecular level, and multifaceted interplay mechanisms underlying polymyxin resistance in P. aeruginosa.

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Some or all data, models, or code generated or used during the study are available from the corresponding author by request.

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Acknowledgements

This work was supported by grants from the Special Foundation for National Science and Technology Basic Research Program of China (2019FY101200, 2019FY101209), the Yunnan Health Training Project of High Level Talents (Grant No: H-2018075), and the Yunnan High-Level Personnel Training Support Plan (Grant No: YNWR-QNBJ-2020-261).

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Author notes

  1. Yuan Liang and Jie Li contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China

    Yuan Liang, Jie Li, Yunmin Xu, Yuan He, Bo Jiang, Chunyan Wu, Bin Shan, Hongqiong Shi & Guibo Song

  2. Yunnan Key Laboratory of Laboratory Medicine, Kunming, 650032, China

    Yuan Liang, Jie Li, Yunmin Xu, Yuan He, Bo Jiang, Chunyan Wu, Bin Shan, Hongqiong Shi & Guibo Song

  3. Yunnan Province Clinical Research Center for Laboratory Medicine, Kunming, 650032, China

    Yuan Liang, Jie Li, Yunmin Xu, Yuan He, Bo Jiang, Chunyan Wu, Bin Shan, Hongqiong Shi & Guibo Song

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Liang, Y., Li, J., Xu, Y. et al. Genomic variations in polymyxin-resistant Pseudomonas aeruginosa clinical isolates and their effects on polymyxin resistance. Braz J Microbiol 54, 655–664 (2023). https://doi.org/10.1007/s42770-023-00933-3

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