Determining the diversity and functionality of antimicrobial resistance genes encoded by Klebsiella spp

Overview

Klebsiella spp. are found in a range of different environments. They are early colonisers and commensals of human skin, oral, nasal, throat and gut microbiotas, but also contribute to a wide range of nosocomial infections (e.g. pneumonia, wound, urinary tract or bloodstream infections, sepsis). Infections caused by Klebsiella pneumoniae are increasingly associated with multidrug resistance, with Klebsiella pneumoniae the most studied species of the genus Klebsiella because of its contribution to the global burden of antimicrobial resistance (AMR). However, reports on AMR in all Klebsiella spp. are increasing, and most members of the genus Klebsiella have been reported as emerging opportunistic pathogens of humans and other animals.

The beta-lactamases SHV and OXY are core to members of the Klebsiella pneumoniae and Klebsiella oxytoca complexes, respectively, providing these bacteria with intrinsic resistance to antibiotics such as ampicillin. Recent work in our laboratory has shown that known and novel members of the Klebsiella planticola and Klebsiella terrigena complexes also encode core beta-lactamases conferring resistance to penicillins. beta-Lactamases encoded by KPC, OXA-48 and NDM genes are found in some clinical isolates of Klebsiella, are associated with multidrug resistance and contribute directly to treatment failures in clinical settings.

We have found that Klebsiella spp. encode a range of uncharacterized AMR genes. Some, or all, of these genes may be functional. If they are functional, they may represent an unrecognized contributor to the global burden of AMR. This project will combine computational- and laboratory-based approaches to characterize the full range of beta-lactamases encoded by Klebsiella spp. Full training will be provided in relevant bioinformatics and data science skills to the student who takes on this exciting and ambitious project.

You will be part of the Antimicrobial Resistance, Omics and Microbiota (AROM) research theme based on the Clifton Campus of Nottingham Trent University (NTU). In addition to attending weekly AROM meetings, where you will have the opportunity to present your work, you will be encouraged to present your work at national and international scientific conferences and to publish your research findings in peer-reviewed journals. You will also receive additional relevant training through events and activities organised through NTU's Doctoral School and the School of Science and Technology.