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.