Michael R. Wessels, MD
|Hospital Title||Chief, Division of Infectious Diseases|
|Academic Title||John F. Enders Professor of Pediatrics and Professor of Medicine (Microbiology and Immunology)|
300 Longwood Avenue
Boston MA 02115
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.
About Michael Wessels
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.
- Jiang S-M, Ishmael N, Hotopp JD, Puliti M, Tissi L, Kumar N, Cieslewicz MJ, Tettelin H, Wessels MR. Variation in the group B Streptococcus CsrRS regulon and effects on pathogenicity. J. Bacteriol. 2008; 190:1956-1965.
- Gryllos I, Tran-Winkler HJ, Cheng M-F, Chung H, Bolcome R, Lu W, Lehrer RI, Wessels MR. Induction of group A Streptococcus virulence by a human antimicrobial peptide. Proc. Natl. Acad. Sci. USA 2008; 105:16755-16760.
- Cortés G, Wessels MR. Inhibition of dendritic cell maturation by group A Streptococcus. J. Infect. Dis. 2009; 200:1152-61.
- Logsdon LK, Hakansson AP, Cortes G, Wessels MR. Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus. mBio 2011; Feb 15;2(1). pii: e00332-10
- Tran-Winkler HJ, Love JF, Gryllos I, Wessels MR. Signal transduction through CsrRS confers an invasive phenotype in group A Streptococcus. PLoS Pathog. 2011; 7(10): e1002361.