Open AccessSurvival ofTropheryma whipplei, the Agent of Whipple's Disease, Requires Phagosome Acidification
Author(s) -
Éric Ghigo,
Christian Capo,
Marianne Aurouze,
Ching–Hsuan Tung,
JeanPierre Gorvel,
Didier Raoult,
JeanLouis Mège
Publication year - 2002
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.70.3.1501-1506.2002
Subject(s) - tropheryma whipplei , phagosome , biology , whipple's disease , bafilomycin , phagolysosome , vacuole , microbiology and biotechnology , lysosome , whipple disease , cathepsin d , cathepsin , phagocytosis , biochemistry , autophagy , enzyme , medicine , coeliac disease , apoptosis , disease , pathology , intestinal malabsorption , cytoplasm
Tropheryma whipplei was established as the agent of Whipple's disease in 2000, but the mechanisms by which it survives within host cells are still unknown. We show here that T. whipplei survives within HeLa cells by controlling the biogenesis of its phagosome. Indeed, T. whipplei colocalized with lysosome-associated membrane protein 1, a membrane marker of late endosomal and lysosomal compartments, but not with cathepsin D, a lysosomal hydrolase. This defect in phagosome maturation is specific to live organisms, since heat-killed bacilli colocalized with cathepsin D. In addition, T. whipplei survived within HeLa cells by adapting to acidic pH. The vacuoles containing T. whipplei were acidic (pH 4.7 +/- 0.3) and acquired vacuolar ATPase, responsible for the acidic pH of late phagosomes. The treatment of HeLa cells with pH-neutralizing reagents, such as ammonium chloride, N-ethylmaleimide, bafilomycin A1, and chloroquine, increased the intravacuolar pH and promoted the killing of T. whipplei. The ability of T. whipplei to survive in an acidic environment and to interfere with phagosome-lysosome fusion is likely critical for its prolonged persistence in host cells during the course of Whipple's disease. Our results suggest that manipulating the intravacuolar pH may provide a new approach for the treatment of Whipple's disease.