Recent emergence of cephalosporin resistant Salmonella Typhi carrying IncFIB(K) plasmid encoding blaCTX-M-15 gene in India

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 blaCTX-M-15 gene, along with other resistance determinants such as aph(3"), aph(6), sul2, dfrA14, qnrS, and tetA. 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). SNP-based phylogenetic analysis of the core genes in IncFIB(K) reveals a close genetic relationship between the plasmid backbone and that of IncFIB(K) from other Enterobacterales, suggesting that the 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 (WASH) systems, is crucial in areas where MDR or XDR S. Typhi strains are prevalent to curb the spread and impact of these resistant strains. ImportanceTyphoid fever remains a significant public health problem in many parts of the world, particularly in resource-limited settings with inadequate sanitation and limited access to clean water. The emergence of MDR S. Typhi resistant to first-line antibiotics (chloramphenicol, ampicillin, and cotrimoxazole) and fluoroquinolones marked the initial treatment challenge, leading to reliance on azithromycin and third-generation cephalosporins. Recently, researchers identified the emergence of XDR typhoid in Pakistan that is resistant to five classes of antibiotics including third-generation cephalosporins. In this study, we report a recent emergence of S. Typhi isolates resistant to third-generation cephalosporins. Genomic characterization and evolutionary analysis of the new strains revealed a recent acquisition of blaCTX-M carrying IncFIB(K) plasmid led to the emergence of ceftriaxone-resistant S. Typhi. Due to the ongoing nature of this outbreak, the data from this study deserves further consideration in order to control its spread in India.