Cnm is a major virulence factor of invasive Streptococcus mutans and part of a conserved three-gene locus.
Cnm, a collagen- and laminin-binding protein present in a subset of Streptococcus mutans strains, mediates binding to extracellular matrices (ECM), intracellular invasion and virulence in the Galleria mellonella model. Antibodies raised against Cnm were used to confirm expression and the cell surface localization of Cnm in the highly invasive OMZ175 strain. Sequence analysis identified two additional genes (cnaB and cbpA) encoding putative surface proteins immediately upstream of cnm. Inactivation of cnaB and cbpA in OMZ175, individually or in combination, did not decrease the ability of this highly invasive and virulent strain to bind to different ECM proteins, invade human coronary artery endothelial cells (HCAEC), or kill G. mellonella. Similarly, expression of cnaB and cbpA in the cnm(-) strain UA159 revealed that these genes did not enhance Cnm-related phenotypes. However, integration of cnm in the chromosome of UA159 significantly increased its ability to bind to collagen and laminin, invade HCAEC, and kill G. mellonella. Moreover, the presence of antibodies against Cnm nearly abolished the ability of OMZ175 to bind to collagen and laminin and invade HCAEC, and significantly protected G. mellonella against OMZ175 infection. We concluded that neither CnaB nor CbpA is necessary for the expression of Cnm-related traits. We also provided definitive evidence that Cnm is an important virulence factor and a suitable target for the development of novel preventive and therapeutic strategies to combat invasive S. mutans strains.
['Avilés-Reyes|A|A|', 'Miller|J H|JH|', 'Simpson-Haidaris|P J|PJ|', 'Lemos|J A|JA|', 'Abranches|J|J|']
D018829:Adhesins, Bacterial D000818:Animals D000907:Antibodies, Bacterial D001422:Bacterial Adhesion D001426:Bacterial Proteins D002352:Carrier Proteins D002460:Cell Line D003094:Collagen D042783:Endothelial Cells D005109:Extracellular Matrix D056426:Genetic Loci D006801:Humans D007797:Laminin D008565:Membrane Proteins D009036:Moths D013290:Streptococcal Infections D013295:Streptococcus mutans D037521:Virulence Factors
Cnm Streptococcus mutans intracellular invasion collagen-binding protein