Bactericidal action of Tat (47-58) peptide via attenuation of cell defense systems

Cells contain a variety of proteins, including those forming a cellular defense system against oxidative stress and DNA damage. In this study, we examined the antibacterial effect of Tat (47–58) peptide, a cell-penetrating peptide, derived from human immunodeficiency virus-1 by focusing on the glutathione and SOS response. First, total glutathione levels were measured to reveal the cellular defense capacity against oxidative stress. Tat (47–58) decreased total glutathione and generated excessive reactive oxygen species, leading to oxidative damage. Second, the expression of RecA protein, which activates the SOS response system in bacterial cells, was detected. Tat (47–58) induced the expression of RecA protein by damaging chromatin and DNA; these actions were confirmed by DAPI and TUNEL staining. Moreover, membrane depolarization and phosphatidylserine exposure, regarded as apoptotic markers, were observed in Tat (47–58)-treated cells. In conclusion, the bactericidal action of Tat (47–58) attenuated the cellular defense systems, including the antioxidant defense system and DNA repair system, and induced apoptosis-like death of Escherichia coli.