Cnm is a major virulence factor of invasive Streptococcus mutans and part of a conserved three‐gene locus. (30th October 2013)

• Record Type: Journal Article
• Authors: Avilés‐Reyes, A.; Miller, J.H.; Simpson‐Haidaris, P.J.; Lemos, J.A.; Abranches, J.
• Is Part Of: Molecular oral microbiology. Volume 29:Number 1(2014:Feb.)
• Page Start: 11
• Page End: 23
• Publication Date: 2013-10-30
• Subjects: Mouth -- Microbiology -- Periodicals; Respiratory infections -- Microbiology -- Periodicals; Mouth -- Diseases -- Immunological aspects -- Periodicals; 617.522
• DOI: 10.1111/mom.12041
• Languages: English
• ISSNs: 2041-1006

Abstract

<abstract abstract-type="main" id="omi12041-abs-0001"> <title>Summary</title> <p>Cnm, a collagen‐ and laminin‐binding protein present in a subset of <italic>Streptococcus mutans</italic> strains, mediates binding to extracellular matrices (ECM), intracellular invasion and virulence in the <italic>Galleria mellonella</italic> 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 (<italic>cnaB</italic> and <italic>cbpA</italic>) encoding putative surface proteins immediately upstream of <italic>cnm</italic>. Inactivation of <italic>cnaB</italic> and <italic>cbpA</italic> 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 <italic>G. mellonella</italic>. Similarly, expression of <italic>cnaB</italic> and <italic>cbpA</italic> in the <italic>cnm</italic><sup>−</sup> strain UA159 revealed that these genes did not enhance Cnm‐related phenotypes. However, integration of <italic>cnm</italic> in the chromosome of UA159 significantly increased its ability to bind to collagen and laminin, invade HCAEC, and kill <italic>G. mellonella</italic>. 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 <italic>G. mellonella</italic> 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 <italic>S. mutans</italic> strains.</p> </abstract>