BBS Faculty Member - Michael Wessels

Michael Wessels

Department of Pediatrics
Department of Microbiology and Immunobiology

Boston Children's Hospital
Infectious Diseases, Enders Bldg., Rm. 761
300 Longwood Ave.
Boston, MA 02115
Tel: 617-919-2900
Fax: 617-730-0254
Email: michael.wessels@childrens.harvard.edu
Lab Members: 4 postdoctoral fellows



Research our laboratory 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.

We 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 how these toxins prevent bacterial entry and modulate intracellular survival by induction of autophagy and disruption of phagolysosomal function.

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. The lab is particularly interested in bacterial detection of environmental changes within the infected host. Experimental infection models are being used to assess the role of CsrRS signaling in bacterial adaptation in this setting and its implications for pathogenesis.



Last Update: 6/5/2014



Publications

For a complete listing of publications click here.

 


 



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