Research in the laboratory of Michael Wessels is concerned with understanding the molecular interactions between pathogen and host in infections due to two species of hemolytic streptococci, S. pyogenes (group A Streptococcus, GAS) and S. agalactiae (group B Streptococcus , GBS). These bacteria can colonize mucosal surfaces as harmless commensals, but both species have the potential to produce local infection or systemic, life-threatening disease.

Current projects are investigating how specific products of GAS alter the biology of pharyngeal epithelial cells, thereby modulating epithelial barrier integrity and innate immune responses at the mucosal surface. The hyaluronic acid capsular polysaccharide of GAS acts an adhesin by binding to CD44, a hyaluronic acid-binding protein on pharyngeal epithelial cells. Signaling through CD44 alters host cell morphology and epithelial integrity, thereby enhancing GAS penetration of the epithelial barrier. The secreted toxins streptolysin O and NADase interfere with uptake of GAS by epithelial cells and antigen presenting cells and prevent killing of internalized GAS by lysosomal fusion. Current studies are characterizing the intracellular trafficking pathways that are modulated by the action of these toxins in host cells and exploring the implications for innate and adaptive immune responses.

In both GAS and GBS, the CsrRS two-component regulatory system controls expression of multiple virulence determinants in response to environmental signals. Ongoing studies are investigating the nature of the stimuli that interact with the CsrS sensor component of this system in each species, as well as the molecular events involved in signal transduction to the CsrR transcriptional regulator and modulation of target gene expression. Transcriptional profiling with whole genome microarrays aims to define the global regulon of bacterial factors controlled by this system in response to specific environmental signals. Experimental infection models are being used to assess the role of CsrRS signaling in bacterial adaptation in the infected host.