Recent emergence of cephalosporin resistant Salmonella Typhi in India due to the endemic clone acquiring IncFIB(K) plasmid encoding blaCTX-M-15 gene

The emergence and spread of Salmonella Typhi ( S . Typhi) resistant to third generation cephalosporins are a serious global health concern. In this study, we have genomically characterized 142 cephalosporin resistant S . Typhi strains isolated from Gujarat, India. Comparative genome analysis of study isolates revealed the emergence of a new clone of ceftriaxone-resistant S . Typhi harboring 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 of bla CTX-M-15 gene, as well as other resistance determinants such as aph(3″) , aph(6′ ), sul2 , dfrA14,qnrS and tetA . Phylogenetic analysis of strains revealed that the isolates from Gujarat ( n=140 / 142 ) belong to a distinct subclade (genotype 4.3.1.2.2) within genotype 4.3.1.2 (H58 lineage II). SNP-based phylogenetic analysis of the core genes in IncFIB(K) suggested a close relatedness of the plasmid backbone to that of IncFIB(K) from other Enterobacteriales. This implies that H58 lineage II can acquire MDR plasmids from other Enterobacteriales provided compensatory evolution balances the associated fitness costs. Although, as previously reported, exposure to the third generation cephalosporins during treatment may have selected for these variants, this could indicate the potential onset of a new wave of ceftriaxone-resistant S . 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. ### Competing Interest Statement The authors have declared no competing interest.