Paratype: A genotyping framework and an open-source tool for Salmonella Paratyphi A

Background: Salmonella enterica serovar Paratyphi A (Salmonella Paratyphi A) is the primary causative agent of paratyphoid fever, which is responsible for an estimated 3.4 million infections annually. However, little genomic information is available on population structure, antimicrobial resistance (AMR), and spatiotemporal distribution of the pathogen. With rising antimicrobial resistance and no licensed vaccines, genomic surveillance is important to track the evolution of this pathogen and monitor transmission. Results: We performed whole-genome sequencing of 817 Salmonella Paratyphi A isolates collected from Bangladesh, Nepal, and Pakistan and added publicly available 562 genomes to build a global database representing 37 countries, covering 1917-2019. To track the evolution of Salmonella Paratyphi A, we used the existing lineage scheme, developed earlier based on a small dataset, but certain sub-lineages were not homologous, and many isolates could not be assigned a lineage. Therefore, we developed a single nucleotide polymorphism based genotyping scheme, Paratype, a tool that segregates Salmonella Paratyphi A into three primary and nine secondary clades, and 18 genotypes. Each genotype has been assigned a unique allele definition located on a conserved gene. Using Paratype, we identified genomic variation between different sampling locations and specific AMR markers, and mutations in the O2-polysaccharide synthesis locus, a candidate for vaccine development. Conclusions: This large-scale global analysis proposes the first genotyping tool for Salmonella Paratyphi A. Paratype has already been released (https://github.com/CHRF-Genomics/Paratype) as an open-access, command-line tool and is being adopted for large scale genomic analysis. This tool will assist future genomic surveillance and help inform prevention and treatment strategies.