Research press release


Nature Microbiology

Anti-psychotic drugs treat meningitis-causing infection in mice

精神障害の治療によく用いられるフェノチアジンが、マウスの髄膜炎菌Neisseria meningitidis感染の治療にも使用できることを明らかにした論文が、今週掲載される。フェノチアジンが、ヒトの重症感染患者にも安全かつ有効かを見極めるには、臨床試験が必要となる。


Sandrine Bourdoulousたちは、これまで殺菌作用はほとんど知られていなかったフェノチアジンが、髄膜炎菌の粘着性付属器の働きを阻害して、培養液中で凝集塊を分散させることを見いだした。さらに、ヒトの通常用量と同等の用量のフェノチアジンをマウスに投与すると、凝集塊の発生と血管壁の損傷が抑制され、マウスの死亡が防がれることが明らかになった。この効果は、標準的な抗生物質と組み合わせて用いることでさらに高まった。


Phenothiazines, drugs that are often used to treat psychotic disorders, can be used to combat Neisseria meningiditis infection in mice, according to a study published online this week in Nature Microbiology. Clinical trials will be needed to determine whether phenothiazines are safe and effective in human patients with severe infections.

The bacterium N. meningitidis can cause organ damage and penetrate the blood-brain barrier to cause meningitis, both of which have high fatality rates. In severe disease, N. meningitidis uses its sticky bacterial appendages to clump together and cling to the inside of blood vessels. Traditional antibiotics that kill bacteria are not effective at disrupting existing clumps.

Sandrine Bourdoulous and colleagues find that phenothiazines, which have been previously shown to be poor at killing bacteria, can block N. meningitidis bacteria from using their sticky appendages, and disperses clumps in culture. The authors then show that these drugs (at similar doses to those what is used in humans) can prevent clumps, blood vessel damage and lethal disease in mice. They found that this effect improved when used in combination with a standard antibiotic.

The study suggests that anti-virulence drugs that disarm, but do not kill, N. meningiditis are effective at treating severe disease. The non-traditional approach may be useful for other infections since many bacteria rely on sticky appendages to cause disease.

doi: 10.1038/s41564-019-0395-8


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