CTX-M variants on the move: Tracking resistance in Escherichia coli and Klebsiella spp. across humans, livestock and wildlife in Western Uganda

Antimicrobial resistance (AMR) is a major global public health challenge. The AMR burden is disproportionately higher in low- and middle-income countries (LMICs), where widespread and inappropriate antimicrobial use promotes the emergence and spread of resistance. The expanding human population and increasing habitat fragmentation of natural areas force wildlife into greater contact with humans and livestock, facilitating AMR transmission. This study aimed to assess the occurrence of extended spectrum cephalosporin (ESC)-resistant Enterobacterales as an indicator for AMR burden across the human-animal-environment interface in rural areas from Western Uganda. Samples were collected from humans ( n = 65), livestock ( n = 137), wildlife ( n = 301), and environmental sources ( n = 52) in rural areas with varying levels of human-animal interaction. ESC-resistant Escherichia coli ( n = 58) and Klebsiella spp.(n = 5) were identified and antimicrobial susceptibility testing was performed. Thereafter, whole genome sequencing was carried out in ESC-resistant isolates ( n = 63) to characterize resistance genes and lineages, and further compared them with previously published sequences from Uganda. A high prevalence of the CTX-M-15 gene was observed, alongside CTX-M-27 and OXA-1. Multiple sequence types (STs) were detected for both E. coli and Klebsiella spp., though globally dominant extraintestinal pathogenic E. coli (ExPEC) lineages were infrequent. The wide occurrence of ESC-resistant bacteria in community settings and wildlife underlines the interconnectedness of AMR transmission. These findings emphasize the need for a comprehensive One Health approach to better understand AMR transmission dynamics in rural areas from Western Uganda.