Lecturer in Molecular Microbiology
My research focuses on determining the molecular basis of treatment refractory infections and the development of novel therapeutic approaches to overcome antibiotic resistance and tolerance. Specifically, I am engaged in research that follows four main themes:
- Molecular mechanisms of host adaptation and the evolution of antibiotic resistance. During the course of infection, Staphylococcus aureus frequently acquires mutations that enhance host adaptation or decrease antibiotic susceptibility. We have identified several genes in which mutations influence bacterial susceptibility to antibiotics, including the Agr quorum-sensing system. In particular, we have identified a novel mechanism of antibiotic resistance that enables S. aureus to survive exposure to daptomycin, a treatment of last resort for MRSA infections.
- Molecular basis of bacterial survival in the host. S. aureus is a frequent cause of serious infections in both humans and animals, including infective endocarditis and bovine mastitis. We are currently engaged in studies to determine the host and bacterial factors that contribute to pathogen survival during infection.
- Regulation of antibiotic tolerance. Despite the frequent difficulty associated with clearing staphylococcal bone and joint infections, almost nothing is known about the mechanisms by which S. aureus evades killing by antibiotics to which it is deemed susceptible via laboratory testing. We have identified a key role for global regulatory elements and putative effectors that modulate the antibiotic tolerance of S. aureus in the host environment.
- Novel approaches to overcoming antibiotic resistance. We are developing new antibiotics to selectively target resistant organisms, without damaging the microbiome.
Pader V, Edwards AM, 2017, Daptomycin: new insights into an antibiotic of last resort, Future Microbiology, Vol:12, ISSN:1746-0913, Pages:461-464
et al., 2017, The Electron Transport Chain Sensitizes Staphylococcus aureus and Enterococcus faecalis to the Oxidative Burst, Infection and Immunity, Vol:85, ISSN:0019-9567
Ledger EVK, Pader V, Edwards AM, 2017, Enterococcus faecalis and pathogenic streptococci inactivate daptomycin by releasing phospholipids, Microbiology-sgm, Vol:163, ISSN:1350-0872, Pages:1502-1508
et al., 2017, Staphylococcus aureus inactivates daptomycin by releasing membrane phospholipids, Nature Microbiology, Vol:2, ISSN:2058-5276
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