Staphylococcus aureus is a highly virulent and widely successful human pathogen, which is speculated to be the most common cause of human disease. Currently, S. aureus is the leading agent of nosocomial infections worldwide, causing a variety of ailments in a plethora of ecological niches within the host. These can range from the relatively benign, such as soft tissue infections, boils, cellulitis and abscesses; to the systemic and life-threatening, such as endocarditis, septic arthritis, osteomyelitis, pneumonia, necrotizing fasciitis and septicemia. This startling array of pathologies is facilitated by a vast arsenal of virulence determinants encoded within the genome of S. aureus, all of which are tightly regulated both temporally and spatially throughout its pathogenic lifestyle.This is achieved through an army of regulatory mechanisms that encompass DNA-binding proteins, two-component regulators, sigma factors and quorum sensing mechanisms. From the perspective of pathogenesis, this wide-reaching network of regulation presumably exists to fine-tune the requirements of the organism within the host environment. Consequently, the need for a thorough analysis of the regulatory networks of S. aureus is of paramount importance, and vital to our understanding of the virulent lifestyle of this organism; and to our ability to combat the devastating infections it causes. This is further compounded by the advent of wide-spread antibiotic resistance in S. aureus, and the emergence of clinical isolates that are resistant to last resort glycopeptide antibiotics. Thus the search for novel antimicrobial targets is crucial in our fight against a return to the pre-antibiotic era, where bacterial infections carried mortality rates of up to 80%. Therefore research in my laboratory focuses on a specific molecular analysis of the regulatory networks of S. aureus, so as to better understand how they contribute to the ability of this organism to cause disease. The ultimate aim of this research is to identify novel targets for therapeutic intervention, so as to circumnavigate this growing problem of antibiotic resistance.
Bacillus anthracis is sporulating, gram-positive pathogen of animals and humans, and is the causative agent of anthrax. It occurs naturally in the soil in spore-form, where it can survive seemingly indefinitely in a dormant and protected state. When ingested by animals or humans, the spore will germinate, leading to the development of the anthrax condition. The infectious dose of the organism is less than 50 individual spores, and without treatment more than 90% of cases prove fatal within a matter of days. Surprisingly little is known about this frighteningly effective bacterial killer, which has attracted attention in recent years as a potential agent for bioterrorist attacks. Research on this organism in my laboratory focuses on the specific molecular events that occur within the Bacillus anthracis cell and spore that contribute to its persistence and pathogenesis.