[ODP-110/W6-5] パラ百日咳菌の産生するメラニンは宿主内における菌の生存を促進する
Bordetella parapertussis causes respiratory infection in humans with a mild pertussis (whooping cough)-like disease. The organism produces a brown pigment, the nature and biological significance of which have not been elucidated. Here, by screening a transposon library we demonstrate that the gene encoding 4-hydroxyphenylpyruvate dioxygenase (HppD) is responsible for production of this pigment. Our results also indicate that the brown pigment produced by the bacterium is melanin, because HppD is involved in the biosynthesis of a type of melanin called pyomelanin and homogentisic acid, the monomeric precursor of pyomelanin, was detected by high-performance liquid chromatography-mass spectrometry analyses. In an infection assay using macrophages, the hppD-deficient mutant was internalized by THP-1 macrophage-like cells similar to the wild-type strain, but was less able to survive within the cells, indicating that melanin protects B. parapertussis from intracellular killing in macrophages. Mouse infection experiments also showed that the hppD-deficient mutant was eliminated from the respiratory tract more rapidly compared to the wild-type strain, although the initial colonization levels were comparable between the two strains. Taken together, our findings indicate that melanin produced by B. parapertussis confers a survival advantage to the bacterium during host infection.