The genomic characterization of Salmonella Paratyphi A from an outbreak of enteric fever in Vadodara, India

Abstract

Salmonella enterica Typhi (S. Typhi) and Paratyphi A (S. Paratyphi A) are the causative agents of enteric fever, a systemic human disease with a burden of 300 000 cases per year in India. The majority of enteric fever cases are associated with S. Typhi, resulting in a paucity of data regarding S. Paratyphi A, specifically with respect to genomic surveillance and antimicrobial resistance (AMR). Here, we exploited whole-genome sequencing (WGS) to identify S. Paratyphi A genotypes and AMR determinants associated with an outbreak of S. Paratyphi A in Vadodara, India, from December 2018 to December 2019. In total 117 S. Paratyphi A were isolated and genome sequenced, most were genotype 2.4.2 (72.6 % of all cases), which is the globally dominant genotype. The remainder were genotype 2.3 (25.6 %), while only two isolates belonged to genotype 2.4.1. A single base-pair mutation in gyrA, associated with reduced susceptibility to fluoroquinolones, was present in all of the outbreak isolates; with 74.35 % of isolates having a S83F substitution and the remainder having an S83Y substitution. Our surveillance study suggests that S. Paratyphi A is an emergent pathogen in South Asia, which may become increasingly relevant with the introduction of Vi conjugate vaccines.

Keywords: Enteric fever; India; Outbreak; Paratyphoid; QRDR.

Fig. 1.

The population structure and genotype distribution of S. Paratyphi A isolates in a Vadodara outbreak. (a) Bar graph showing the genotype distribution of S. Paratyphi A across time. (b) SNP-based maximum-likelihood phylogenetic tree of 117 S. Paratyphi A isolates from Vadodara. Different branch colours highlight the genotypes identified. From left to right, annotations show the month of isolation, QRDR mutation (gyrA) and the presence of a plasmid represented with a black star.

Fig. 2.

Phylogenetic representation of S. Paratyphi A isolates from Vadodara in a global context SNP-based maximum-likelihood phylogenetic tree of 966 global S. Paratyphi A isolates including the 117 Vadodara isolates. Different branch colours highlight identified genotypes. Clades for the isolates from the Vadodara outbreak are highlighted in yellow, 71 genomes isolated in the same time period from UK travellers to India are highlighted in grey and the clade for the reference genome S. Paratyphi A AKU12601 is highlighted in orange. From the inside, ring 1 and 2 correspond to the year and country of isolation, respectively, and ring 3 shows the QRDR mutations identified.