Comparative molecular profiling of multidrug-resistant Pseudomonas aeruginosa identifies novel mutations in regional clinical isolates from South India.

Autor: Menon ND; School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India.; Antimicrobial Resistance, Tata Institute for Genetics and Society (TIGS), Bangalore, India., Somanath P; School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India.; Antimicrobial Resistance, Tata Institute for Genetics and Society (TIGS), Bangalore, India., Jossart J; Department of Molecular Diagnostics and Experimental Therapeutics, City of Hope, Duarte, CA, USA., Vijayakumar G; School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India.; Antimicrobial Resistance, Tata Institute for Genetics and Society (TIGS), Bangalore, India., Shetty K; School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India.; Antimicrobial Resistance, Tata Institute for Genetics and Society (TIGS), Bangalore, India., Baswe M; School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India.; Antimicrobial Resistance, Tata Institute for Genetics and Society (TIGS), Bangalore, India., Chatterjee M; School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India.; Antimicrobial Resistance, Tata Institute for Genetics and Society (TIGS), Bangalore, India., Hari MB; School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India.; Antimicrobial Resistance, Tata Institute for Genetics and Society (TIGS), Bangalore, India., Nair S; Department of Microbiology, DDRC SRL Diagnostic Private Limited, Trivandrum, Kerala, India., Kumar VA; Department of Microbiology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India., Nair BG; School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India.; Antimicrobial Resistance, Tata Institute for Genetics and Society (TIGS), Bangalore, India., Nizet V; Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA.; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA., Perry JJP; Department of Molecular Diagnostics and Experimental Therapeutics, City of Hope, Duarte, CA, USA., Kumar GB; School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India.; Antimicrobial Resistance, Tata Institute for Genetics and Society (TIGS), Bangalore, India.
Jazyk: angličtina
Zdroj: JAC-antimicrobial resistance [JAC Antimicrob Resist] 2024 Jan 16; Vol. 6 (1), pp. dlae001. Date of Electronic Publication: 2024 Jan 16 (Print Publication: 2024).
DOI: 10.1093/jacamr/dlae001
Abstrakt: Objectives: We sought to analyse the antibiotic susceptibility profiles and molecular epidemiology of MDR clinical Pseudomonas aeruginosa isolates from South India using non-MDR isolates as a reference.
Methods: We established a comprehensive clinical strain library consisting of 58 isolates collected from patients across the South Indian state of Kerala from March 2017 to July 2019. The strains were subject to antibiotic susceptibility testing, modified carbapenem inactivation method assay for carbapenemase production, PCR sequencing, comparative sequence analysis and quantitative PCR of MDR determinants associated with antibiotic efflux pump systems, fluoroquinolone resistance and carbapenem resistance. We performed in silico modelling of MDR-specific SNPs.
Results: Of our collection of South Indian P. aeruginosa clinical isolates, 74.1% were MDR and 55.8% were resistant to the entire panel of antibiotics tested. All MDR isolates were resistant to levofloxacin and 93% were resistant to meropenem. We identified seven distinct, MDR-specific mutations in nalD , three of which are novel. mexA was significantly overexpressed in strains that were resistant to the entire test antibiotic panel while gyrA and gyrB were overexpressed in MDR isolates. Mutations in fluoroquinolone determinants were significantly associated with MDR phenotype and a novel GyrA Y100C substitution was observed. Carbapenem resistance in MDR isolates was associated with loss-of-function mutations in oprD and high prevalence of NDM ( bla NDM-1 ) within our sample.
Conclusions: This study provides insight into MDR mechanisms adopted by P. aeruginosa clinical isolates, which may guide the potential development of therapeutic regimens to improve clinical outcomes.
(© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)
Databáze: MEDLINE
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