DIVERSE GENETIC BACKGROUND OF MULTIDRUG RESISTANT PSEUDOMONAS AERUGINOSA CIRCULATING IN INDIA

Abstract

Intro: Pseudomonas aeruginosa is an opportunistic pathogen and is associated with serious infections, and treatment can be challenging. Rates of antimicrobial resistance (AMR), multidrug-resistant (MDR) infections are increasing. Our objective was to characterize the epidemiology and AMR mechanisms of this pathogen circulating in India using whole genome sequencing. Methods: 312 P.aeruginosa isolates recovered from 21 hospital sites in India between 2017–2022 were seqeunced. Isolates were subjected to antimicrobial susceptibility testing by Vitek-2 automated system, and their genomes were assembled from Illumina sequencing data. MLST type, virulence genes, AMR determinants, and relatedness between isolates were derived; and determined concordance between phenotypic and genotypic resistance. Findings: β-lactam resistance was high (99.6%), with 99.6%to Cephalosporins, 98.3%to Aminoglycosides, 96.4%to Phenicols, 54.8% to Fluroquinolones, 36% to carbapenem and 17.6% to Macrolides. Carbapenem resistance was associated mainly with acquisition of the MBLs-blaOXA genes and blaNDM1 gene. Loss of function of the OprD-porin was observed in 4 isolates. KPC-2 was detected in 5 isolates and blaVIM gene was not detected. Concordance between phenotypic and genotypic resistance was 99.5% overall. Virulence genes, toxA (94.8%), plcH (98.3%), lasA/B/I (99.6%), exoS (51.6%), exoT (97.1%), exoU (48%), exoX (90%) were detected. Genotyping by MLST revealed 80 different sequence types. The population of P.aeruginosa was diverse, with MLSTs ST357, ST308, ST235, ST244 and ST654 predominant. About 13.7%of STs were of novel types and were found to emerge from the high-risk clones, having 100% resistance to Beta lactams and Cephalosporins, 90% resistance to Aminoglycosides and harbouring diverse virulence genes. Most of the ST357 and Novel ST genomes formed a distinct lineage from global genomes, thus raising the possibility that they may be unique to the India. Conclusion: The survey bridges the gap in genomic data from India. The association of resistance determinants with phylogenetic background displays the utility of WGS-monitoring AMR in P.aeruginosa. The presence of resistance and virulence determinants throughout phylogenetic tree shows that knowledge of local epidemiology is crucial for guiding potential treatment of MDR P. aeruginosa infections.