Heterologous expression of Streptococcus mutans Cnm in Lactococcus lactis promotes intracellular invasion, adhesion to human cardiac tissues and virulence

Author(s)

Freires, Irlan A. ; Aviles-Reyes, Alejandro ; Kitten, Todd ; Simpson-Haidaris, P. J. ; Swartz, Michael ; Knight, Peter A. ; Rosalen, Pedro L. ; Lemos, Jose A. ; Abranches, Jacqueline

• Document type: Journal article
• Source: VIRULENCE; v. 8, n. 1, p. 18-29, 2017.
• Web of Science Citations: 11

Abstract

In S. mutans, the expression of the surface glycoprotein Cnm mediates binding to extracellular matrix proteins, endothelial cell invasion and virulence in the Galleria mellonella invertebrate model. To further characterize Cnm as a virulence factor, the cnm gene from S. mutans strain OMZ175 was expressed in the non-pathogenic Lactococcus lactis NZ9800 using a nisin-inducible system. Despite the absence of the machinery necessary for Cnm glycosylation, Western blot and immunofluorescence microscopy analyses demonstrated that Cnm was effectively expressed and translocated to the cell wall of L. lactis. Similar to S. mutans, expression of Cnm in L. lactis enabled robust binding to collagen and laminin, invasion of human coronary artery endothelial cells and increased virulence in G. mellonella. Using an ex vivo human heart tissue colonization model, we showed that Cnm-positive strains of either S. mutans or L. lactis outcompete their Cnm-negative counterparts for tissue colonization. Finally, Cnm expression facilitated L. lactis adhesion and colonization in a rabbit model of infective endocarditis. Collectively, our results provide unequivocal evidence that binding to extracellular matrices mediated by Cnm is an important virulence attribute of S. mutans and confirm the usefulness of the L. lactis heterologous system for further characterization of bacterial virulence factors. (AU)

• FAPESP's process: 14/07231-0 - Prevalence of Cnm-expressing Streptococcus mutans and the role of this glycoprotein on platelet activation and adherence to cardiac tissues
• Grantee: Irlan de Almeida Freires
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 13/25080-7 - Prevalence of strains of Streptococcus mutans expressing Cnm in children and adults, and the role of this glycoprotein in the pathogen-host interactions
• Grantee: Irlan de Almeida Freires
• Support Opportunities: Scholarships in Brazil - Doctorate