title: RD1 region in mycobacterial genome is involved in the induction of necrosis in infected RAW264 cells via mitochondrial membrane damage and ATP depletion.
abstract: It was shown that virulent Mycobacterium tuberculosis H37Rv induces necrosis of infected RAW264 cells at 24 h post infection while avirulent H37Ra and an attenuated H37Rv mutant that is deficient for RD1 region (H37RvDeltaRD1) cause less necrosis of the infected cells. While H37Rv caused damage of the mitochondrial inner membrane and decreased the level of intracellular ATP, H37RvDeltaRD1 did not exhibit these harmful effects in infected cells. On the other hand, there was no difference in the level of intracellular reactive oxygen species after infection with H37Rv or H37RvDeltaRD1, and the intracellular bacterial numbers of H37RvDeltaRD1 and H37Ra were comparable to that of H37Rv. These results suggested that some virulence factors of H37Rv may contribute to the necrosis of infected cells through induction of mitochondrial dysfunction and depletion of intracellular ATP. RD1 appeared to encode some components possibly playing a central role in the induction of host cell necrosis after M. tuberculosis infection.
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Taijin
authors.initials: T
authors.lastname: Kaku
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kawamura
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Uchiyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurenuma
authors.forename: Masao
authors.initials: M
authors.lastname: Mitsuyama
mesh_terms: D000255:Adenosine Triphosphate / Q000172:deficiency* / Q000378:metabolism; D002460:Cell Line; D004269:DNA, Bacterial / Q000235:genetics; D016680:Genome, Bacterial; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000502:physiology*; D009336:Necrosis / Q000503:physiopathology; D016366:Open Reading Frames; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004269:DNA, Bacterial; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate