title: Contribution of biofilm regulatory protein A of Streptococcus mutans, to systemic virulence.
abstract: Streptococcus mutans is occasionally isolated from the blood of patients with bacteremia and infective endocarditis (IE), and the possibility that it could be pathogenic for those diseases has been discussed. The initial important step for the involvement of bacterial pathogens in the virulence of IE is thought to be survival in blood for an extended period. Recently, the brpA gene encoding biofilm regulatory protein A (BrpA) of S. mutans was cloned and sequenced, after which it was shown that inactivation of brpA in an isogenic mutant strain resulted in longer chain formation than in the parental strain. In the present study, a BrpA-defective isogenic mutant strain (MT8148BRD) was constructed from strain MT8148. In an analysis of its susceptibility to phagocytosis by human polymorphonuclear leukocytes (PMNs), the phagocytosis rate of MT8148BRD was shown to be significantly lower than that of MT8148 (P < 0.01). Next, strains with various chain lengths were produced by culturing MT8148 in media with various initial pH levels, which revealed that there was a statistically negative correlation between phagocytosis susceptibility and chain length (P < 0.01). Further, MT8148BRD was found to possess higher platelet aggregation properties than MT8148 (P < 0.05). In addition, injection of MT8148BRD into the jugular vein of specific pathogen-free Sprague-Dawley rats resulted in a longer duration of bacteremia, which prolonged systemic inflammation for a longer period than in those infected with MT8148. These results indicate that S. mutans BrpA is associated with virulence in blood, due to its correlation to phagocytosis susceptibility and platelet aggregation properties.
authors.affiliation: Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry, 1-8 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakano
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Fujita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Nishimura
authors.forename: Ryota
authors.initials: R
authors.lastname: Nomura
authors.forename: Takashi
authors.initials: T
authors.lastname: Ooshima
mesh_terms: D000818:Animals; D016470:Bacteremia; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology*; D017353:Gene Deletion; D006801:Humans; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D010974:Platelet Aggregation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013290:Streptococcal Infections / Q000821:virology*; D013295:Streptococcus mutans / Q000166:cytology / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; C454866:BrpA protein, Streptococcus mutans; D037521:Virulence Factors