A contemporary genomic snapshot of Salmonella Paratyphi A in Pakistan

<i>Salmonella enterica</i> 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 <i>S</i>. Typhi, <i>S</i>. 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 <i>S</i>. 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 <i>gyrA</i> mutations. Although multidrug resistance was not detected, we identified one isolate harbouring an <i>acrB</i>-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 <i>S</i>. Paratyphi A in Pakistan, essential for future surveillance, AMR monitoring, and evaluating the potential impact of forthcoming paratyphoid vaccines.