An exploration of unusual antimicrobial resistance phenotypes in Salmonella Typhi from Blantyre, Malawi reveals the ongoing role of IncHI1 plasmids

Typhoid fever is a significant public health problem endemic in Southeast Asia and Sub- Saharan Africa. Antimicrobial treatment of typhoid is however threatened by the increasing prevalence of antimicrobial resistant (AMR) S. Typhi, especially in the globally successful lineage (4.3.1) which has rapidly spread in East and Southern Africa. AMR elements can be found either on plasmids or in one of the three chromosomal integration sites, and there is variability of this across the lineage. Several previous studies with Malawian isolates indicated a clonal, locally spreading lineage with chromosomally integrated resistance genes. In a recent study however we noted three isolates with unusual predicted resistance profiles, and we here present the resolved genomes of these isolates using long- and short-read sequencing. Our work shows that these isolates are potentially imported cases, most closely related to the recently described sub-lineage 4.3.1.EA1, and encode IncHI1 plasmids with reduced resistance profiles compared to the major reference sequence of these plasmids spreading in East Africa. Similar reduced resistance plasmids were reported in a recent large-scale study in five isolates from Tanzania, highlighting the urgency for better coverage of the African continent in genome studies to better understand the dynamics of these potentially co-circulating plasmids.