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Cnm is a major virulence factor of invasive S treptococcus mutans and part of a conserved three‐gene locus
Author(s) -
AvilésReyes A.,
Miller J.H.,
SimpsonHaidaris P.J.,
Lemos J.A.,
Abranches J.
Publication year - 2014
Publication title -
molecular oral microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 77
eISSN - 2041-1014
pISSN - 2041-1006
DOI - 10.1111/omi.12041
Subject(s) - virulence , biology , microbiology and biotechnology , gene , streptococcus mutans , galleria mellonella , virulence factor , laminin , locus (genetics) , extracellular matrix , genetics , bacteria
Summary Cnm, a collagen‐ and laminin‐binding protein present in a subset of S treptococcus mutans strains, mediates binding to extracellular matrices ( ECM ), intracellular invasion and virulence in the G alleria mellonella model. Antibodies raised against C nm were used to confirm expression and the cell surface localization of C nm in the highly invasive OMZ 175 strain. Sequence analysis identified two additional genes ( cna B and cbp A ) encoding putative surface proteins immediately upstream of cnm . Inactivation of cna B and cbp A in OMZ 175, 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 cna B and cbp A in the cnm − strain UA 159 revealed that these genes did not enhance C nm‐related phenotypes. However, integration of cnm in the chromosome of UA 159 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 OMZ 175 to bind to collagen and laminin and invade HCAEC , and significantly protected G. mellonella against OMZ 175 infection. We concluded that neither C na B nor C bp A is necessary for the expression of C nm‐related traits. We also provided definitive evidence that C nm is an important virulence factor and a suitable target for the development of novel preventive and therapeutic strategies to combat invasive S . mutans strains.