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

Author:

Menon Nitasha D12ORCID,Somanath Priyanka12ORCID,Jossart Jennifer3,Vijayakumar Gayathri12,Shetty Kavya12,Baswe Manasi12,Chatterjee Meghna12,Hari Malavika B12,Nair Samitha4,Kumar V Anil5ORCID,Nair Bipin G12,Nizet Victor678,Perry J Jefferson P3,Kumar Geetha B12ORCID

Affiliation:

1. School of Biotechnology, Amrita Vishwa Vidyapeetham , Amritapuri, Kerala , India

2. Antimicrobial Resistance, Tata Institute for Genetics and Society (TIGS) , Bangalore , India

3. Department of Molecular Diagnostics and Experimental Therapeutics, City of Hope , Duarte, CA , USA

4. Department of Microbiology, DDRC SRL Diagnostic Private Limited , Trivandrum, Kerala , India

5. Department of Microbiology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham , Kochi, Kerala , India

6. Department of Pharmacology, University of California, San Diego , La Jolla, CA , USA

7. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego , La Jolla, CA , USA

8. Department of Pediatrics, University of California, San Diego , La Jolla, CA , USA

Abstract

Abstract 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 (blaNDM-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.

Funder

Tata Institute for Genetics and Society

Amrita Vishwa Vidyapeetham

University Grants Commission of India

Publisher

Oxford University Press (OUP)

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