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Open Access Publications from the University of California

The Fibrinogen-binding M1 Protein Reduces Pharyngeal cell Adherence and colonization Phenotypes of M1T1 Group A Streptococcus

  • Author(s): Anderson, EL
  • Cole, JN
  • Olson, J
  • Ryba, B
  • Ghosh, P
  • Nizet, V
  • et al.

Background: The group A Streptococcus (GAS) M1 protein binds fibrinogen (Fg) to block phagocytosis and to form a proinflammatory complex. Results: M1 and Fg limit GAS adherence and invasion of pharyngeal keratinocytes in vitro. Conclusion: Protease SpeB modulates M1 expression and GAS host cell interactions differentially during the course of infection. Significance: M1 protein is shown to impede pharyngeal colonization in vivo. Group A Streptococcus (GAS) is a leading human pathogen producing a diverse array of infections from simple pharyngitis ("strep throat") to invasive conditions, including necrotizing fasciitis and toxic shock syndrome. The surface-Anchored GAS M1 protein is a classical virulence factor that promotes phagocyte resistance and exaggerated inflammation by binding host fibrinogen (Fg) to form supramolecular networks. In this study, we used a virulentWTM1T1GASstrain and its isogenic M1-deficient mutant to examine the role of M1-Fg binding in a proximal step in GAS infection-interaction with the pharyngeal epithelium. Expression of the M1 protein reduced GAS adherence to human pharyngeal keratinocytes by 2-fold, and this difference was increased to 4-fold in the presence of Fg. In stationary phase, surfaceM1protein cleavage by theGAScysteine protease SpeB eliminated Fg binding and relieved its inhibitory effect on GAS pharyngeal cell adherence. In a mouse model of GAS colonization of nasal-Associated lymphoid tissue, M1 protein expression was associated with an average 6-fold decreasedGAS recovery in isogenic strain competition assays. Thus, GAS M1 protein-Fg binding reduces GAS pharyngeal cell adherence and colonization in a fashion that is counterbalanced by SpeB. Inactivation of SpeB during the shift to invasive GAS disease allows M1-Fg binding, increasing pathogen phagocyte resistance and proinflammatory activities.© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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