Sensing the Host, One Signal at a Time and All at Once
Our research aims to understand how Staphylococcus aureus senses, adapts, and responds to chemical signals of innate immunity that would be encountered during colonization, and at sites of infection.
Approximately 30% of the human population is persistently colonized by S. aureus, most frequently in the nose, and S. aureus also typically persists on the skin of colonized individuals. To persist on its human host, S. aureus must recognize and integrate different chemical signals from innate immunity and respond in an appropriate manner to evade killing by innate defence mechanisms, the main pillars of which include exposure to acidic pH, antimicrobial peptides, and antimicrobial fatty acids.
With this as a broad mandate
RND-family efflux pumps
Regulation and function of a Resistance-Nodulation-Division superfamily efflux pump that is induced by and required for resistance to antimicrobial unsaturated fatty acids encountered at sites of colonization and infection.
Reading concurrent signals
Understanding how S. aureus senses and responds to concurrent exposure to different signals from innate immunity (i.e. combinations of antimicrobial peptides, antimicrobial fatty acids, and growth at acidic pH). Bacteria do not have the option of dealing with one stress at a time; they must efficiently sense and respond to disparate antimicrobial threats that are encountered simultaneously.
Nutrient or toxin?
Elucidating how S. aureus metabolism of host-derived antimicrobial unsaturated free fatty acids is influenced by conditions that mimic in vivo growth. S. aureus cannot synthesize unsaturated fatty acids, which are toxic if allowed to accumulate in the cytoplasmic membrane. How do the bacteria optimize the use of host-derived antimicrobial fatty acids as a nutrient, while minimizing toxicity?
Why the membrane is the whole story
Innate immunity doesn't attack S. aureus with a single weapon; it presents a mixture of acidic pH, antimicrobial peptides, and antimicrobial fatty acids simultaneously, at the cell envelope. Our work sits at the interface of bacterial genetics, membrane biology, and physiology: identifying the sensors and regulators that detect these signals, and tracing how that detection is converted into a survival response, from gene regulation through to fatty acid handling at the membrane itself.