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

Abstract

The emergence and spread of Salmonella Typhi (S. Typhi) resistant to third-generation cephalosporins is a serious global health concern. In this study, we genomically characterized 142 cephalosporin-resistant S. Typhi strains isolated from India. Comparative genome analysis revealed the emergence of a new clone of ceftriaxone-resistant S. Typhi harboring three plasmids of the incompatibility groups IncFIB(K), IncX1, and IncFIB(pHCM2). Among these, the IncFIB(K) plasmid confers resistance to third-generation cephalosporins through the bla_CTX-M-15 gene, along with other resistance determinants such as aph(3"), aph(6'), sul2, dfrA14, qnrS, and tet(A). Phylogenetic analysis showed 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). Single nucleotide polymorphism-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, indicating that H58 lineage II possesses the capability to acquire MDR plasmids from these organisms. 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 and improved water, sanitation, and hygiene systems—is crucial in areas where MDR or extensively drug-resistant S. Typhi strains are prevalent to curb the spread and impact of these resistant strains.