Abstract
Hydrogen peroxide (H2O2) is a debriding agent that damages the microbial structure and function by generating various reactive oxygen species (ROS). H2O2-produced hydroxyl radical (OH∙) also exerts oxidative stress on microorganisms. The spread of antibiotic-resistance in bacteria is a serious issue worldwide, and greater efforts are needed to identify and characterize novel antibacterial mechanisms to develop new treatment strategies. Therefore, this study aimed to clarify the relationship between H2O2 and Escherichia coli and to elucidate a novel antibacterial mechanism(s) of H2O2. Following H2O2 exposure, increased levels of 8-hydroxydeoxyguanosine and malondialdehyde indicated that H2O2 accelerates oxidation of bacterial DNA and lipids in E. coli. As oxidative damage worsened, the SOS response was triggered. Cell division arrest and resulting filamentous cells were identified in cells, indicating that LexA was involved in DNA replication. It was also verified that RecA, a representative SOS gene, helps self-cleavage of LexA and acts as a bacterial caspase-like protein. Our findings also showed that dinF is essential to preserve E. coli from H2O2-induced ROS, and furthermore, demonstrated that H2O2-induced SOS response and SOS genes participate differently in guarding E. coli from oxidative stress. As an extreme SOS response is considered apoptosis-like death (ALD) in bacteria, additional experiments were performed to examine the characteristics of ALD. DNA fragmentation and membrane depolarization appeared in H2O2-treated cells, suggesting that H2O2 causes ALD in E. coli. In conclusion, our investigations revealed that ALD is a novel antibacterial mode of action(s) of H2O2 with important contributions from SOS genes.
Highlights
Hydrogen peroxide (H2O2) is a colorless, toxic liquid that causes oxidative stress in many organisms
These findings suggest that H2O2 forms OH∙ within E. coli, and that OH∙ created by H2O2 decomposition may trigger oxidative damage to bacteria
In that its pharmacological activities are effective in treating microbial infection, it is necessary to elucidate the therapeutic effects of H2O2 in greater detail (Amanna, et al 2012, McDonnell 2009)
Summary
Hydrogen peroxide (H2O2) is a colorless, toxic liquid that causes oxidative stress in many organisms. H2O2 is an apoptosis inducer because it exerts a broad cytotoxic efficacy on most types of cells (Xiang, et al 2016) It induces apoptosis by acting as an apoptotic signaling molecule, exerting its effect through changes in pro- and anti-apoptotic protein expression, DNA damage, mitochondrial cytochrome c release, and caspase9/caspase-3 activation (Saito, et al 2006, Singh, et al 2007). A high concentration of H2O2 is involved in the stress response of fungi, which causes cell death, and thereby serves as a fungicide (Glass and Dementhon 2006). It exhibits bactericidal activity by either inhibiting cell proliferation or oxidizing bacterial cell walls (Linley, et al 2012). Proper concentration of H2O2 is known to cure chronic skin wounds, and the application of an appropriate H2O2 concentration helps to treat bacterial infections (Mueller, et al 2012, Zhu, et al 2017)
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