The streptococcal collagen-like protein-1 (Scl1) is a multifunctional adhesin in extracellular matrix interactions, biofilm formation, and host colonization by group A Streptococcus

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

The streptococcal collagen-like protein-1 (Scl1) is a significant determinant for biofilm formation by group a Streptococcus

<p>Abstract</p> <p>Background</p> <p>Group A <it>Streptococcus </it>(GAS) is a human-specific pathogen responsible for a number of diseases characterized by a wide range of clinical manifestations. During host colonization GAS-cell aggregates or microcolonies are observed in tissues. GAS biofilm, which is an <it>in vitro </it>equivalent of tissue microcolony, has only recently been studied and little is known about the specific surface determinants that aid biofilm formation. In this study, we demonstrate that surface-associated streptococcal collagen-like protein-1 (Scl1) plays an important role in GAS biofilm formation.</p> <p>Results</p> <p>Biofilm formation by M1-, M3-, M28-, and M41-type GAS strains, representing an intraspecies breadth, were analyzed spectrophotometrically following crystal violet staining, and characterized using confocal and field emission scanning electron microscopy. The M41-type strain formed the most robust biofilm under static conditions, followed by M28- and M1-type strains, while the M3-type strains analyzed here did not form biofilm under the same experimental conditions. Differences in architecture and cell-surface morphology were observed in biofilms formed by the M1- and M41-wild-type strains, accompanied by varying amounts of deposited extracellular matrix and differences in cell-to-cell junctions within each biofilm. Importantly, all Scl1-negative mutants examined showed significantly decreased ability to form biofilm <it>in vitro</it>. Furthermore, the Scl1 protein expressed on the surface of a heterologous host, <it>Lactococcus lactis</it>, was sufficient to induce biofilm formation by this organism.</p> <p>Conclusions</p> <p>Overall, this work (i) identifies variations in biofilm formation capacity among pathogenically different GAS strains, (ii) identifies GAS surface properties that may aid in biofilm stability and, (iii) establishes that the Scl1 surface protein is an important determinant of GAS biofilm, which is sufficient to enable biofilm formation in the heterologous host <it>Lactococcus</it>. In summary, the GAS surface adhesin Scl1 may have an important role in biofilm-associated pathogenicity.</p

Group A Streptococcus

The streptococcal collagen-like protein-1 (Scl1) i