First report of third-generation cephalosporin-resistant clinical isolate of Salmonella Bareilly ST203 harbouring plasmid-mediated AmpC β-lactamase CMY6 from India: Genome characteristics and transmissibility.

Non-typhoidal Salmonella (NTS) infections are a major public health concern in India because of inadequate knowledge of antimicrobial resistance, limiting therapeutic options. The study aimed to characterize and analyse the genome of a 3rd-generation cephalosporins (3GCs)-resistant clinical isolate of Salmonella Bareilly-harbouring plasmid-mediated AmpC (pAmpC) CMY-6. Identification, antibiotic susceptibility and Whole Genome Sequencing (WGS)-based analysis were performed. Transmissibility, replicon types of blaCMY-6-harbouring plasmid were evaluated. S. Bareilly ST203 (Clonal-Complex 206.2) was isolated from clinical specimen of a paediatric patient and was found to be multidrug-resistant with resistance to 3rd generation cephalosporins, fluoroquinolone and aminoglycosides. WGS revealed pAmpC blaCMY-6 on conjugative IncC plasmid (158,385 kb) which successfully transferred into the transconjugant with other resistance determinants (blaTEM-1A, armA, aac(6')-Ib-cr, sul1), showed higher MICs for 3GCs. Downstream regions of blaCMY-6 include blc (lipocalin), sugE (efflux protein) and truncated ecnR (entericidin R) followed by other resistance genes. Presence of ISEcp1 in the genome facilitated the transfer of blaCMY-6. Several efflux pump genes, two complete CRISPR arrays and intact phage sequences were also detected. Virulence factors associated with Salmonella Pathogenicity Islands SPI-1/SPI-2/SP-3 and their effectors indicated the virulence potential of this strain. To the best of our knowledge, genome of a 3GCs-resistant clinical isolate of S. Bareilly-harbouring pAmpC blaCMY-6 was reported and analysed for the first time in this study. S. Bareilly was found to cause outbreaks in earlier reports but lower resistance was reported in this serovar compared to other NTS. As infections by NTS are concerning, early detection of such strains is of utmost importance.