Invasion of human coronary artery endothelial cells by Streptococcus mutans: molecular mechanisms of pathogenesis.

Project: Research

Investigators

  • Jacqueline Abranches (PI)

Description

Dissemination of oral bacteria into the bloodstream is common in patients subjected to dental procedures such as tooth extraction, endodontic treatment, and periodontal surgery. Streptococcus mutans, the etiologic agent of dental caries, is frequently implicated in cardiovascular diseases (CVD), especially infective endocarditis (IE). Recently, S. mutans was identified as the most prevalent bacterial species found in heart vegetations and atheromatous plaque. Based on this clinical evidence, we evaluated the capacity of S. mutans isolated from dental plaque and from blood of patients with bacteremia and endocarditis, to invade human coronary artery endothelial cells (HCAEC). We showed for the first time that S. mutans strains belonging to serotype e and f are capable of invading HCAEC. Among the tested strains, two serotype f strains, OMZ175 and NCTC 11060, displayed the most invasive behavior with an average 0.22% (approx. 4.4 x 104 CFU) of the initial inoculum able to reach HCAEC intracellular compartment. Interestingly, we found that only invasive strains carry an additional gene (cnm) coding for a collagen-binding protein. By knocking out cnm in OMZ175, we demonstrated that Cnm is critical for HCAEC invasion, and contributes to S. mutans virulence in the killing of Galleria mellonella, an invertebrate model commonly used to study bacterial pathogenesis. Our working hypothesis is that both non-invasive and invasive S. mutans strains can elicit IE, but only strains carrying cnm can invade the valve tissue contributing to disease severity, persistent infection and chronic inflammatory responses. The first goal of this proposal is to fully characterize the role of Cnm in the invasion process of HCAEC by S. mutans. The second goal of this proposal is to use an established rabbit model for IE to show that invasive (cnm+) strains are more virulent than non-invasive strains, and to localize invasive S. mutans in the vegetation and heart valve tissue. The findings from this proposal will: (i) show the relevance of invasion to the pathogenesis of IE, (ii) reveal the potential use of Cnm as a biomarker for screening patients that might need to receive preventive treatment prior to dental procedures, and (iii) possibly identify a novel target for the development of new therapeutic approaches to treat or prevent IE.
Award amount$192,288.00
Award date07/01/2010
Program typeGrant-in-Aid
Award ID10GRNT4210049
Effective start/end date07/01/201006/30/2013
StatusFinished