Date of Graduation
School of Medicine
Microbiology, Immunology, and Cell Biology
Group A Streptococcus (GAS) is responsible for over 100 million skin infections annually that may lead to invasive episodes and autoimmune sequelaes. Wounds and unapparent skin infringements are susceptible to the introduction of GAS and serve as a portal of entry. The nutritional nature of a wound and the accessibility to exposed host cell surfaces and extracellular matrix components create a model milieu for successful host colonization and potential biofilm formation. The initiation of biofilm is often mediated by bacterial surface adhesins and has been shown to interfere with wound healing by blocking critical host cellular interactions. However, the underlying molecular mechanisms supporting this impediment of wound healing are not completely understood. Here, we characterize the GAS surface adhesin, streptococcal collagen-like protein-1 (Scl1), and its interaction with extracellular matrix components and contribution to GAS biofilm formation. Scl1 has been detected in all GAS strains and extends from the GAS surface as a homotrimeric protein composed of a collagen-like domain, structurally similar to mammalian collagen, and an adjacent amino-terminal non-collagenous variable domain. The current work (i) identifies that the Scl1 variable domain binds to extracellular matrix proteins, cellular fibronectin and laminin and contributes to GAS adherence and internalization (ii) demonstrates that the Scl1 protein is an important determinant of GAS biofilm formation on untreated and ECM-deposited surfaces, and (iii) characterizes a novel molecular mechanism by which GAS utilizes the Scl1 protein to specifically target the EDA-containing variant of cellular fibronectin predominantly expressed at the site of injured tissue in order to secure host colonization and biofilm formation. In total, these studies further demonstrate the importance of the Scl1 protein in GAS pathogenesis.
Oliver-Kozup, Heaven A., "The streptococcal collagen-like protein-1 (Scl1) is a multifunctional adhesin in extracellular matrix interactions, biofilm formation, and host colonization by group A Streptococcus" (2013). Graduate Theses, Dissertations, and Problem Reports. 570.