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Genetic determinants of antimicrobial resistance in polymyxin B resistant Pseudomonas aeruginosa isolated from airways of patients with cystic fibrosis

  • Clinical Microbiology – Research Paper
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Abstract

Pseudomonas aeruginosa is the main pathogen associated with pulmonary exacerbation in patients with cystic fibrosis (CF). CF is a multisystemic genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, which mainly affects pulmonary function. P. aeruginosa isolated from individuals with CF in Brazil is not commonly associated with multidrug resistance (MDR), especially when compared to global occurrence, where the presence of epidemic clones, capable of expressing resistance to several drugs, is often reported. Due to the recent observations of MDR isolates of P. aeruginosa in our centers, combined with these characteristics, whole-genome sequencing was employed for analyses related to antimicrobial resistance, plasmid identification, search for phages, and characterization of CF clones. All isolates in this study were polymyxin B resistant, exhibiting diverse mutations and reduced susceptibility to carbapenems. Alterations in mexZ can result in the overexpression of the MexXY efflux pump. Mutations in oprD, pmrB, parS, gyrA and parC may confer reduced susceptibility to antimicrobials by affecting permeability, as observed in phenotypic tests. The phage findings led to the assumption of horizontal genetic transfer, implicating dissemination between P. aeruginosa isolates. New sequence types were described, and none of the isolates showed an association with epidemic CF clones. Analysis of the genetic context of P. aeruginosa resistance to polymyxin B allowed us to understand the different mechanisms of resistance to antimicrobials, in addition to subsidizing the understanding of possible relationships with epidemic strains that circulate among individuals with CF observed in other countries.

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Acknowledgements

We express our profound gratitude for the technical assistance provided by the Laboratory of Bacteriology at Hospital Universitario Pedro Ernesto (HUPE-UERJ).

Funding

This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) /MCTI/CT-Saúde No 52/2022 - Ações em Ciência, Tecnologia e Inovação para o enfrentamento da Resistência Antimicrobiana (RAM), Processo: 408725/2022-2 and Projeto REDES - Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Faperj E-26/211.554/2019.

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  1. Laboratório de Microbiologia da Fibrose Cística, Departamento de Microbiologia, Imunologia e Parasitologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

    Felipe A. Simão, Mila M. Almeida, Heloísa S. Rosa, Elizabeth A. Marques & Robson S. Leão

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  1. Felipe A. Simão
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Contributions

All author contributed to the study conception and design. In terms of the manuscript composition and information acquisition, FAS played a primary role as the main contributor. Bioinformatics assistance and writing were provided by MMA, while HSR facilitated the search process and comprehension of bioinformatics tools. Corrective measures, content structuring, and information consolidation were carried out with the contributions of EAM and RSL. The first draft of the manuscript was written by FAS, MMA, EAM and RSL, and all authors commented on previous versions of the manuscript. All authors read and approved the final version of the manuscript.

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Correspondence to Robson S. Leão.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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All procedures performed in this study were in accordance with the ethical standards of the institutional research committee (CAAE: 79547616.1.0000.5259), and the approval was waived by the local Ethics Committee of Universidade do Estado do Rio de Janeiro, in view of the retrospective nature of the study and all the procedures were performed with samples stored in a bacteriological collection.

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Simão, F.A., Almeida, M.M., Rosa, H.S. et al. Genetic determinants of antimicrobial resistance in polymyxin B resistant Pseudomonas aeruginosa isolated from airways of patients with cystic fibrosis. Braz J Microbiol (2024). https://doi.org/10.1007/s42770-024-01311-3

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  • DOI: https://doi.org/10.1007/s42770-024-01311-3

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