Mitochondrial alterations precede Bordetella pertussis-induced apoptosis.
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 (deltapsim) 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 deltapsim. deltapsim 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 deltapsim disruption in the cascade of events leading to B. pertussis-induced apoptosis.
Bachelet
Maria
M
Laboratoire de Physiologie Respiratoire, UFR Cochin Port Royal, Paris, France. marie.bachelet@chusa.jussieu.fr
Richard
Marie Jeanne
MJ
François
Dominique
D
Polla
Barbara S
BS
D000255:Adenosine Triphosphate / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D017209:Apoptosis; D001886:Bordetella pertussis / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000382:microbiology / Q000502:physiology* / Q000648:ultrastructure; D009000:Monocytes / Q000166:cytology / Q000378:metabolism / Q000382:microbiology / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D000255:Adenosine Triphosphate; D000242:Cyclic AMP