Conjugative IncHI1 plasmids drive the emergence of multidrug resistance in Nigerian Salmonella Typhi: A four-decade genomic analysis.

BACKGROUND

The role of plasmids in driving antimicrobial resistance (AMR) in West African Salmonella Typhi remains unexplored. This study investigates the prevalence, temporal dynamics, and genetic associations of plasmid mobility classes and replicon types in Nigerian S. typhi over nearly four decades.

RESULTS

We analyzed 151 S. typhi genomes from Nigeria (1982-2018) obtained from EnteroBase. Plasmid replicon typing and mobility classification revealed that 49.7% of isolates harbored conjugative plasmids, with the IncHI1 family (IncHI1A, IncHI1B_R27, and IncFIA_HI1) being the most prevalent. Conjugative plasmids increased from 0% in the 1980s to 56% in the 2010s (logistic regression, p = 0.006). A core multidrug resistance element comprising blaTEM-1B, sul1, catA1, dfrA15, and tet(B) was identified in 49% of isolates. Strong statistical associations were observed between IncHI1 plasmids and these AMR genes, with phi coefficients reaching r = 0.95 for tet(B), r = 0.87 for blaTEM-1B, and r = 0.86 for sul1. Isolates carrying conjugative plasmids harbored nearly five times more AMR genes than non-mobilizable isolates (4.9 vs 0.9; ANOVA, p < 0.001). Temporal breakpoint analysis identified 2010 as the year AMR prevalence exceeded 50%, coinciding with the sharp rise in conjugative plasmid carriage.

CONCLUSION

Conjugative IncHI1 plasmids are the primary drivers of multidrug resistance emergence in Nigerian S. typhi, carrying a conserved core resistome that has spread rapidly since 2010. These findings underscore the critical need for plasmid surveillance in genomic epidemiology and highlight IncHI1 plasmids as key targets for monitoring AMR transmission in high-burden settings.