ABOUT THE RESEARCHER

OVERVIEW

Dr. Wessels’ research is concerned with understanding the molecular interactions between pathogen and host in infections due to Streptococcus pyogenes (group A Streptococcus or GAS), the etiologic agent of streptococcal pharyngitis (strep throat) and severe invasive infections such as necrotizing fasciitis and streptococcal toxic shock. These bacteria can colonize mucosal surfaces as harmless commensals, but they have the potential to produce local infection or systemic, life-threatening disease.

The lab is particularly interested in the molecular dialog between the bacteria and the human host, and how signaling between them affects the outcome of infection. Specific virulence factors such as the secreted toxin streptolysin O and its co-toxin NAD-glycohydrolase (NADase) inhibit uptake and killing of GAS by professional phagocytes (macrophages and neutrophils) and epithelial cells. Recent work in the lab has discovered that SLO and NADase prevent intracellular killing of GAS by blocking maturation of autophagosomes in epithelial cells and by inhibiting phagosomal acidification in macrophages. Current studies are focused on identifying receptors for SLO and NADase and understanding how specific interactions with host cell surface molecules and between the toxins control intoxication of target cells. Research in collaboration with the laboratory of Isaac Chiu is investigating how streptolysin S stimulates pain neurons during invasive infection and impairs host defense.

The expression of these and other virulence determinants is regulated by the CsrRS (CovRS) two-component system in response to specific environmental signals including the human cathelicidin antimicrobial peptide LL-37. Paradoxically, stimulation of LL-37 secretion as part of the host innate immune response appears to signal through CsrRS to upregulate multiple GAS virulence factors, thereby promoting a transition from asymptomatic mucosal colonization to invasive infection. The lab is investigating how the CsrRS system activates expression of certain genes and represses others, and how additional regulatory proteins modulate CsrRS-mediated control of gene expression.

 

BACKGROUND

Michael Wessels received his MD from Duke University. He completed internship and residency at Beth Israel Hospital, Boston and a fellowship at Beth Israel and Brigham and Women's Hospitals.