A contemporary genomic snapshot of Salmonella Paratyphi A in Pakistan.

Salmonella enterica serovar Paratyphi A is a significant but under-characterised cause of enteric fever in South Asia. In Pakistan, where the typhoid conjugate vaccine has been introduced to combat S. Typhi, S. Paratyphi A remains a prominent cause of bacteraemia, raising concerns about shifts in disease burden and antimicrobial resistance (AMR). Here, we provide a comprehensive genomic and phylogenetic analysis of 354 S. Paratyphi A isolates collected from three provinces in Pakistan between 2017 and early 2022. Whole-genome sequencing revealed the dominance of genotypes 2.3.3 and 2.4.5, indicating a largely stable population structure over time, and the presence of widespread fluoroquinolone-associated gyrA mutations. Although multidrug resistance was not detected, we identified one isolate harbouring an acrB-R717Q mutation associated with azithromycin resistance. Plasmid and replicon analysis revealed low prevalence of extrachromosomal elements, including cryptic plasmids with unknown function. Phylogenetic placement of these isolates in a global context demonstrated close relatedness to contemporary South Asian organisms. Our findings establish a genomic baseline for S. Paratyphi A in Pakistan, essential for future surveillance, AMR monitoring, and evaluating the potential impact of forthcoming paratyphoid vaccines.