Open AccessRD1 region in mycobacterial genome is involved in the induction of necrosis in infected RAW264 cells via mitochondrial membrane damage and ATP depletion
Author(s) -
Kaku Taijin,
Kawamura Ikuo,
Uchiyama Ryosuke,
Kurenuma Takeshi,
Mitsuyama Masao
Publication year - 2007
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.2007.00838.x
Subject(s) - microbiology and biotechnology , mitochondrion , tumor necrosis factor alpha , necrosis , chemistry , biology , genetics , immunology
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 (H37RvΔ RD1 ) cause less necrosis of the infected cells. While H37Rv caused damage of the mitochondrial inner membrane and decreased the level of intracellular ATP, H37RvΔ RD1 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 H37RvΔ RD1 , and the intracellular bacterial numbers of H37RvΔ RD1 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.