The Collagen-Binding Protein Cnm Is Required for Streptococcus mutans Adherence to and Intracellular Invasion of Human Coronary Artery Endothelial Cells

<jats:title>ABSTRACT</jats:title> <jats:p> <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Streptococcus mutans</jats:named-content> is considered the primary etiologic agent of dental caries, a global health problem that affects 60 to 90% of the population, and a leading causative agent of infective endocarditis. It can be divided into four different serotypes ( <jats:italic>c</jats:italic> , <jats:italic>e</jats:italic> , <jats:italic>f</jats:italic> , and <jats:italic>k</jats:italic> ), with serotype <jats:italic>c</jats:italic> strains being the most common in the oral cavity. In this study, we demonstrate that in addition to OMZ175 and B14, three other strains (NCTC11060, LM7, and OM50E) of the less prevalent serotypes <jats:italic>e</jats:italic> and <jats:italic>f</jats:italic> are able to invade primary human coronary artery endothelial cells (HCAEC). Invasive strains were also significantly more virulent than noninvasive strains in the <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Galleria mellonella</jats:named-content> (greater wax worm) model of systemic disease. Interestingly, the invasive strains carried an additional gene, <jats:italic>cnm</jats:italic> , which was previously shown to bind to collagen and laminin <jats:italic>in vitro</jats:italic> . Inactivation of <jats:italic>cnm</jats:italic> rendered the organisms unable to invade HCAEC and attenuated their virulence in <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">G. mellonella</jats:named-content> . Notably, the <jats:italic>cnm</jats:italic> knockout strains did not adhere to HCAEC as efficiently as the parental strains did, indicating that the loss of the invasion phenotype observed for the mutants was linked to an adhesion defect. Comparisons of the invasive strains and their respective <jats:italic>cnm</jats:italic> mutants did not support a correlation between biofilm formation and invasion. Thus, Cnm is required for <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">S. mutans</jats:named-content> invasion of endothelial cells and possibly represents an important virulence factor of <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">S. mutans</jats:named-content> that may contribute to cardiovascular infections and pathologies. </jats:p>