Phagosome Acidification Has Opposite Effects on Intracellular Survival ofBordetella pertussisandB. bronchiseptica

Bordetella pertussis is readily killed after uptake by professional phagocytes, whereas its close relativeBordetella bronchiseptica is not and can persist intracellularly for days. Phagocytosis of members of either species by a mouse macrophage cell line results in transport of the bacteria to a phagosomal compartment positive for the lysosome-associated membrane protein 1, the protease cathepsin D, and the late endosomal vacuolar proton-pumping ATPase but negative for the early endosome antigen 1 and the early endosomal transferrin receptor. In addition, we demonstrate thatBordetella -containing phagosomes rapidly acidify to pH 4.5 to 5.0. Taken together, these data demonstrate thatBordetella -containing phagosomes rapidly mature to an acidic late endosomal/lysosomal compartment. Following up on this observation, we determined thatB. pertussis does not survive in bacterial growth media adjusted to a pH of 4.5, whereas this pH has only minor effects on the growth ofB. bronchiseptica . Raising the intracellular pH in infected macrophages by the addition of bafilomycin A1 , ammonium chloride, or monensin increases the survival of acid-sensitiveB. pertussis but, surprisingly, decreases that of acid-tolerantB. bronchiseptica . In summary, we hypothesize that the differential survival ofB. pertussis andB. bronchiseptica in macrophages is, at least in part, due to the differences in their acid tolerance.