Dynamics of Antimicrobial Resistance and Genomic Epidemiology of Multidrug-Resistant Salmonella enterica Serovar Indiana ST17 from 2006 to 2017 in China

The genetic features of foodborne Salmonella have changed in recent years as multidrug-resistant (MDR) strains have become prevalent among various serovars. The recent expansion of MDR Salmonella enterica serovar Indiana sequence type 17 (ST17) poses an increasing threat to global public health, as 24.3% (61/251) of S. Indiana isolates in this study exhibited resistance to three clinically important antimicrobial agents: fluoroquinolones (ciprofloxacin), extended-spectrum β-lactams (cephalosporin), and macrolides (azithromycin). Both the evolutionary histories and antimicrobial resistance (AMR) profiles of this serovar remain to be described. Bioinformatic analysis revealed multiple lineages have coexisted and spread throughout China. Specifically, emergence of a predominant lineage appears to be associated with accumulated various substitutions in the chromosomal quinolone resistance-determining regions (GyrA S83F D87N and ParC T57S S80R) (141 [56.2%]), as well as acquisition of an extended-spectrum β-lactamase (ESBL)-producing IncHI2 plasmid that has subsequently undergone extensive rearrangement and an IncX1 plasmid that contains mph(A), conferring resistance to azithromycin. Several other evolutionary events influencing the trajectory of this drug-resistant serovar were also identified, including sporadic acquisitions of bla(CTX-M)-carrying plasmids, along with chromosomal integration of bla(CTX-M) within subclusters. Most human isolates reside in clusters containing isolates from animals, mainly from chickens, indicating the close relationship of human isolates with those from food animals. These data demonstrate that MDR S. Indiana ST17 is already widespread and capable of acquiring resistance traits against the clinical important antimicrobial agents, suggesting it should be considered a high-risk global MDR pathogen. The complexity of its evolutionary history has implications for AMR surveillance, epidemiological analysis, and control of emerging clinical lineages. IMPORTANCE The emergence and worldwide spread of AMR Salmonella constitute great public health concerns. S. enterica serovar Indiana is a typical MDR serovar characterized by sporadic reports. However, comprehensive population genomics studies have not been performed on this serovar. This study provides a detailed and comprehensive insight into the rapid evolution of AMR in this important Salmonella serovar in the past 15 years in eight provinces of China. We documented diverse contributory genetic processes, including stable chromosomal integrations of resistance genes, the persistence and evolution of mobile resistance elements within sublineages, and sporadic acquisition of different resistance determinants that occur at all genetic levels (genes, genetic contexts, plasmids, and host strains). There are different mechanisms of antimicrobial resistance in S. enterica serovar Indiana from those of other serovars. This study sheds light on the formation of MDR S. enterica serovar Indiana with chickens as its potential reservoirs and paves the way to curb its further expansion among food animals.