Pangenome analysis of salmonella Paratyphi a reveals genetic diversity, antimicrobial resistance determinants, and public health implications.

Salmonella Paratyphi A (SPA) causing paratyphoid fever, a significant health concern in South Asia, particularly in Pakistan. This research aimed to explore the antibiotic resistance pattern, genetic diversity, and the evolutionary dynamics of SPA isolated from suspected paratyphoid patients in Pakistan. Whole-genome sequencing (WGS) of (n = 10) isolates predicted predominantly serotype O-2, H1: a, H2:1,5. Sequence type (ST85) was detected, alongside three STs (ST21eb, ST6d3b, ST95c4) and eight pathogenicity islands. The study reported extensively drug resistant (XDR) isolates (SPA 2,14,27,79) as per the AMR genes detected in IncY and IncQ1 plasmids (blaTEM-1, blaCTX-M-15, sul1, sul2, dfrA7, catA1, qnrS1) along with multiple resistance associated mutations in gyrA (S83F, E133G), gyrB (T14M), ParC (T57S) and AcrB (L40P) genes. These genomic results were co-related with phenotypic resistance exhibited by XDR Paratyphi A isolates against different class of antibiotics. The Paratyphi A strains (SPA 1,2,14,27 and 79) harbored highest number of unique genes determined by pangenome analysis. Interestingly these strains were highly virulent and exhibited XDR profile which indicated significant resistance and virulence genes transfer through horizontal gene transfer mechanism. The phylogenetic Tree constructed by maximum likelihood method showed that eight of the ten SPA isolates of the study belonged to genotype 2.3 as they formed a tight cluster with reference strain (AKU_12601). The present study represents a well-characterized genomic profiling of Salmonella Paratyphi A isolates from Pakistan. The detection of XDR alarms the situation in the country as no XDR reported yet in Paratyphi A. Unavailability of vaccines for Paratyphi A strains further warns of limited treatment and prevention strategies thus possess serious public health threat. The findings emphasize the need for urgent action by public health authorities to mitigate the potential emerging XDR Salmonella Paratyphi A and prevent its future outbreaks in Pakistan.