Open AccessMitochondrial alterations precede Bordetella pertussis ‐induced apoptosis
Author(s) -
Bachelet Maria,
Richard MarieJeanne,
François Dominique,
Polla Barbara S
Publication year - 2002
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2002.tb00544.x
Subject(s) - bordetella pertussis , biology , apoptosis , pertussis toxin , programmed cell death , microbiology and biotechnology , mitochondrion , phagocytosis , immunology , signal transduction , g protein , genetics , bacteria
Bordetella pertussis , the causative agent of whooping cough in humans, secretes a number of toxins, including adenylate cyclase‐hemolysin (AC‐Hly), and induces macrophage apoptosis. We investigated the effects of B. pertussis on mitochondrial membrane potential (ΔΨm) and ATP levels, as possible determinants of cell death. Using the fluorescent probe JC‐1, we found that infection of human monocytes by B. pertussis lead to a disruption in host‐cell ΔΨm. ΔΨm alterations were preceded by a massive increase in cyclic AMP, a moderate decrease in ATP, and was independent from oxidative stress. These changes were observed when human monocytes were infected by the parental B. pertussis 18323 but not when infected by the mutants deficient in the expression of AC‐Hly. Exposure of human monocytes to purified AC‐Hly induced changes comparable to those observed with the B. pertussis parental strain. Our results provide a mechanistic relationship between AC‐Hly, ATP, and ΔΨm disruption in the cascade of events leading to B. pertussis ‐induced apoptosis.