Recent emergence of cephalosporin resistantSalmonellaTyphi carrying IncFIB(K) plasmid encodingblaCTX-M-15gene in India

Abstract

AbstractThe emergence and spread ofSalmonellaTyphi resistant to third generation cephalosporins are a serious global health concern. In this study, we have genomically characterized twelve cephalosporin resistantS. Typhi strains isolated from India. Comparative genome analysis of study isolates revealed the emergence of a new clone of ceftriaxone-resistantS. Typhi containing three plasmids of the incompatibility group IncFIB(K), IncX1 and IncFIB(pHCM2). Among the three, IncFIB(K) plasmid confers resistance to third-generation cephalosporins by means ofblaCTX-M-15gene, as well as other resistance determinants such asaph(3”),aph(6’),sul2,dfrA14andtetA. Phylogenetic analysis of strains revealed that a single isolate belongs to a clade corresponding to genotype 4.3.1 and isolates from Ahmedabad (n=11) belong to a distinct subclade within genotype 4.3.1.2 (H58 lineage II). SNP-based phylogenetic analysis of the core genes in IncFIB(K) revealed the plasmid backbone is closely related to that of IncFIB(K) from other Enterobacterales. The findings suggest that H58 lineage II can acquire MDR plasmids from other Enterobacteriales if compensatory evolution balances the cost of carrying the plasmids. Though, like previously reported, exposure to the third generation cephalosporins during the treatment may have selected these variants, this could indicate the beginning of a new wave of ceftriaxone resistantS. Typhi in India. The implementation of control measures such as vaccination, improved water, sanitation, etc., could be undertaken in areas where MDR or XDR S Typhi strains are prevalent.