In recent years, the increase in the incidence of hypermucoviscous Klebsiella pneumoniae (hvKP) infections has become a clinical concern worldwide. The high pathogenicity of hvKP is in part attributed to the overproduction of capsular polysaccharide (CPS), which is achieved by the action of a positive regulator of capsular polysaccharide synthesis genes, named rmpA. There have been many studies on the mechanism of hvKP virulence, but no study has focused on the development of anti-virulence therapies. We tried to identify antimicrobial drugs that can suppress the hypermucoviscosity of hvKP. As a result, we found that rifampicin (RFP) has a strong anti-mucoviscous activity against hvKP. RFP treatment caused a drastic reduction in the thickness of the CPS layer around hvKP cells and suppressed transcript levels of capsule-related genes including rmpA. Our data suggest that RFP may be useful as a potential anti-virulence agent for intractable infections caused by hvKP.
Between April of 2002 and March of 2004, I worked at University of Minnesota in the US as a visiting researcher. This opportunity was supported by Research grant of Japanese Antibiotics Research Association. Basic research is essential for clinical medicine. This opportunity in the US have change my values and clinical strategy for the diagnosis and treatment of infectious diseases.