The dynamics of bla_TEM resistance genes in Salmonella Typhi

Salmonella Typhi (S. Typhi) is an important pathogen causing typhoid fever worldwide. The emergence of antibiotic resistance, including that of bla_TEM genes encoding to TEM [Formula: see text]-lactamases has been observed. This study aimed to investigate the dynamics of bla_TEM genes in S. Typhi by analyzing the phylogeny and flanking region patterns and phylogenetic associating them with metadata (year, country) and genomic data (genotypes, antibiotic resistance genes (ARGs), plasmids). Genomic sequences of publicly available S. Typhi harboring bla_TEM (n = 6079), spanning from 1983 to 2023, were downloaded and analyzed using CSIPhylogeny for phylogeny, Flankophile for identifying genetic contexts around bla_TEM genes and GenoTyphi for determining genotypes, ARGs and plasmid replicons. We found that bla_TEM-positive isolates occurred most commonly in specific location, especially in Asia and Africa and clustered among a limited number of genotypes. Flankophile identified 740 isolates (12.2%) with distinct flanking region patterns, which were categorized into 13 patterns. Notably, 7 patterns showed a predominantly phylogenetic association with genotypes. Additionally, these 7 patterns exhibited relation to the country, ARGs and plasmid replicons. Further examination of the flanking region patterns provided association with mobile genetic elements (MGEs). Taken together, this study suggests that bla_TEM has been acquired by S. Typhi isolates a limited number of times and subsequently spread clonally with specific genotypes.