Our laboratory investigates antimicrobial resistance (AMR) in Gram-negative Enterobacterales, particularly in Proteus species, using integrated approaches combining genomics and One Health surveillance. Proteus is an important opportunistic pathogen that causes urinary tract and wound infections in clinical settings. It possesses intrinsic resistance to several classes of antibiotics (tetracyclines, polymyxins, nitrofurantoin) and is increasingly showing acquired resistance to carbapenems and broad-spectrum beta-lactams.

Our current research focuses on three interrelated areas. Firstly, we are characterising the prevalence of atypical carbapenemases in Proteus species through whole-genome sequencing and molecular analyses, and investigating the role of horizontal gene transfer, plasmid-mediated resistance determinants and pathogen-related lifestyle factors. Secondly, we conduct cross-source surveillance of antimicrobial resistance in veterinary, environmental and clinical settings across various geographical regions, and use genomic analyses to uncover patterns in the spread of resistance genes and emerging threats. Thirdly, we use experimental evolution under antibiotic selection pressure to identify new genes and mechanisms that contribute to the development of resistance, and generate potential therapeutic targets through comparative genomic analyses of resistant mutants.

To enable the functional characterisation of identified genes, we optimise molecular protocols for targeted gene knockouts in Proteus species using allele exchange based on suicide vectors and genome editing techniques, and establish robust platforms for forward and reverse genetics. Furthermore, we are developing and validating new algorithms for the rapid detection of AMR genes in Enterobacterales. Together, these approaches provide mechanistic insights into the development of resistance and support evidence-based strategies for antibiotic use, as well as the development of the next generation of antibiotics.