The collagen-binding protein of Streptococcus mutans is involved in haemorrhagic stroke

Kazuhiko Nakano; Kazuya Hokamura; Naho Taniguchi; Koichiro Wada; Chiho Kudo; Ryota Nomura; Ayuchi Kojima; Shuhei Naka; Yoshinori Muranaka; Min Thura; Atsushi Nakajima; Katsuhiko Masuda; Ichiro Nakagawa; Pietro Speziale; Nobumitsu Shimada; Atsuo Amano; Yoshinori Kamisaki; Tokutaro Tanaka; Kazuo Umemura; Takashi Ooshima

Although several risk factors for stroke have been identified, one-third remain unexplained. Here we show that infection with Streptococcus mutans expressing collagen-binding protein （CBP） is a potential risk factor for haemorrhagic stroke. Infection with serotype k S. mutans, but not a standard strain, aggravates cerebral haemorrhage in mice. Serotype k S. mutans accumulates in the damaged, but not the contralateral hemisphere, indicating an interaction of bacteria with injured blood vessels. The most important factor for high-virulence is expression of CBP, which is a common property of most serotype k strains. The detection frequency of CBP-expressing S. mutans in haemorrhagic stroke patients is significantly higher than in control subjects. Strains isolated from haemorrhagic stroke patients aggravate haemorrhage in a mouse model, indicating that they are haemorrhagic stroke-associated. Administration of recombinant CBP causes aggravation of haemorrhage. Our data suggest that CBP of S. mutans is directly involved in haemorrhagic stroke.