A TRACE AMOUNT OF THE HUMAN PRO-APOPTOTIC FACTOR BAX INDUCES BACTERIAL DEATH ACCOMPANIED BY DAMAGE OF DNA

An amount of human pro-apoptotic Bar 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. Coexpression of anti-apoptotic Bcl-x(L) showed a modest inhibitory effect on the cell death caused by Bar. The trace amount of Bay elongated E. coli and ac cumulated monounsaturated fatty acids, suggesting an unusual metabolis m of redox in the host. In fact, an increase of KCN-dependent O-2 cons umption accompanied the expression of Bar. At the same time, a fluores cent pH indicator showed the apparent accumulation of protons outside the cell, suggesting that the membrane is intact. Bax increased the le vel of superoxide anion as measured by the expression of superoxide-de pendent promoter. Nicked DNA was significantly generated, and the freq uency of mutations resistant to rifampicin was increased by 30-fold, d epending upon the expression of Bar. It is proposed that trace amounts of Bar increase oxygen consumption, triggering generation of superoxi de, which affects DNA, leading to bacterial death.