OCCURRENCE OF ANTIMICROBIAL RESISTANCE GENES PRIOR TO APPROVAL OF ANTIBIOTICS FOR CLINICAL USE: EVIDENCES FROM COMPARATIVE RESISTOME ANALYSIS OF SALMONELLA ENTERICA SPANNING FOUR DECADES

Abstract

Growing antimicrobial resistance (AMR) in Salmonella spp. is an evolving crisis exacerbated by antibiotic misuse. The present study was undertaken to delineate the temporal trends in the emergence of AMR among Salmonella enterica strains from India. Genome sequences and metadata of Salmonella enterica isolates were obtained from NCBI and were analyzed by the Resistance Gene Identifier tool (Comprehensive Antimicrobial Resistance Database), ABRicate (PlasmidFinderDB), BacAnt (IntegronDB, TransposonDB). Core-genome phylogeny was constructed with Roary and IQ-TREE. Antibiotics approval data were collected from the Central Drug Control Standards Organisation website and were analyzed with SPSS. Overall, AMR genes against 23 antibiotic classes were detected with cephalosporins and fluoroquinolones being at the top (17 genes each). For many antibiotics (monobactams, glycylcyclines, fosfomycins, elfamycins, edeine) occurrences of AMR genes preceded approval of the antibiotic for use. A statistically significant difference (p<0.05) was observed for resistance mechanisms, gene families, and SNP patterns, though no difference was noted for AMR gene carriage among salmonellae at decadal intervals. Our results deciphered the trends of AMR in Indian isolates of Salmonella enterica, highlighting occurrences of AMR genes and mechanisms before antibiotic approval and the usefulness of WGS-based AMR analysis for guiding future policy.