A trace amount of the human pro-apoptotic factor Bax induces bacterial death accompanied by damage of DNA.
An amount of human pro-apoptotic Bax as low as 0.01% of total protein was sufficient to cause cell death in Escherichia coli. The bacterial cell death was examined using a viable bacteria-specific fluorescence indicator system and loss of colony formation ability. Co-expression of anti-apoptotic Bcl-xL showed a modest inhibitory effect on the cell death caused by Bax. The trace amount of Bax elongated E. coli and accumulated monounsaturated fatty acids, suggesting an unusual metabolism of redox in the host. In fact, an increase of KCN-dependent O2 consumption accompanied the expression of Bax. At the same time, a fluorescent pH indicator showed the apparent accumulation of protons outside the cell, suggesting that the membrane is intact. Bax increased the level of superoxide anion as measured by the expression of superoxide-dependent promoter. Nicked DNA was significantly generated, and the frequency of mutations resistant to rifampicin was increased by 30-fold, depending upon the expression of Bax. It is proposed that trace amounts of Bax increase oxygen consumption, triggering generation of superoxide, which affects DNA, leading to bacterial death.
Asoh
S
S
Department of Biochemistry and Cell Biology, Institute of Gerontology, Nippon Medical School, 1-396, Kosugi-cho, Nakahara-ku, Kawasaki-city, Kanagawa 211-0063, Japan.
Nishimaki
K
K
Nanbu-Wakao
R
R
Ohta
S
S
D017209:Apoptosis; D004249:DNA Damage; D004269:DNA, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D013481:Superoxides / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004269:DNA, Bacterial; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D013481:Superoxides; D010100:Oxygen