Bacterial Adhesion & Antivirulence Studies.

Virulence factors enable bacteria to colonize, infect, and cause harm to the host. As such, virulence factors are attractive antimicrobial targets. Indeed, rather than inhibiting growth, antivirulence approaches are designed to neutralize these mechanisms, with the intention of disarming bacteria and reducing pathogenicity.

Bacterial adhesion is often a fundamental and early step in host colonization and infection. We are mainly exploring the genetic and molecular basis underlying adhesion of the human pathogen Staphylococcus aureus to the human host. However, we are also studying adhesion of other bacteria too. We recently developed a sensitive and robust whole cell assay to enable the large-scale profiling of S. aureus adhesion to host ligands. Using this assay, we profiled a sequence-defined S. aureus transposon mutant library, identifying mutants with attenuated adhesion to human-derived fibronectin, keratin, and fibrinogen—three important host ligands (see below figure and Petrie et al., 2021 JBC). Delineating the genetic requirements of S. aureus adhesion provided a more in-depth understanding of the interaction of this organism with the host and we are currently exploring these findings in more detail.

In addition, we are also interested in identifying novel anti-adhesive therapeutics and we are using our recently developed adhesion assay to pioneer a cutting-edge drug discovery campaign. Anti-adhesives could complement our antibiotic arsenal, offering the potential to reduce the severity of the resistance crisis using a more targeted approach.