Lecturer in Molecular Microbiology
Research in my group is focussed on the mechanisms by which pathogens promote population diversity and the consequences of this for persistence in the host, with a particular focus on antibiotic tolerance and resistance.
Much of our work involves the human and animal pathogen Staphylococcus aureus, which is responsible for a raft of superficial and invasive infections, many of which can become chronic despite apparently appropriate antibiotic therapy.
In keeping with other pathogenic bacteria, populations of S. aureus contain sub-populations of cells, known as persisters, which are tolerant of antibiotics. These bacteria are genetically identical to susceptible bacteria but have adopted an altered physiological state which significantly reduces their susceptibility to antibiotics. It is hypothesised that the ability of a small sub-population of bacteria to tolerate therapeutic antibiotics explains why some infections relapse, despite apparently successful antibiotic therapy. We are currently determining the molecular mechanisms of persister formation with a long-term goal of preventing or reversing the antibiotic tolerant state of these bacteria.
Genotypic diversity arises via spontaneous mutation during bacterial replication. However, non-replicating bacteria can also mutate via mutagenic DNA repair pathways. We have identified genes critical for this process in S. aureus and demonstrated that DNA damage caused by oxidative stress or certain antibiotics promotes the emergence of antibiotic-resistant mutants via the action of specific proteins. Blocking the functional domains of these proteins would significantly reduce the rate of emergence of strains resistant to certain antibiotics.
et al., 2016, Staphylococcus aureus inactivates daptomycin by releasing membrane phospholipids., Nat Microbiol, Vol:2
et al., 2015, Staphylococcus aureus Adapts to Oxidative Stress by Producing H2O2-Resistant Small-Colony Variants via the SOS Response, Infection and Immunity, Vol:83, ISSN:0019-9567, Pages:1830-1844
et al., 2014, The Agr Quorum-Sensing System Regulates Fibronectin Binding but Not Hemolysis in the Absence of a Functional Electron Transport Chain, Infection and Immunity, Vol:82, ISSN:0019-9567, Pages:4337-4347
et al., 2014, What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?, Trends in Microbiology, Vol:22, ISSN:0966-842X, Pages:676-685
et al., 2014, Oxacillin Alters the Toxin Expression Profile of Community-Associated Methicillin-Resistant Staphylococcus aureus, Antimicrobial Agents and Chemotherapy, Vol:58, ISSN:0066-4804, Pages:1100-1107