Otto Caitlin C, Koehl Jennifer L, Solanky Dipesh, Haydel Shelley E
School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.
School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America; The Biodesign Institute Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
PLoS One. 2014 Dec 11;9(12):e115172. doi: 10.1371/journal.pone.0115172. eCollection 2014.
Aqueous leachates prepared from natural antibacterial clays, arbitrarily designated CB-L, release metal ions into suspension, have a low pH (3.4-5), generate reactive oxygen species (ROS) and H2O2, and have a high oxidation-reduction potential. To isolate the role of pH in the antibacterial activity of CB clay mixtures, we exposed three different strains of Escherichia coli O157:H7 to 10% clay suspensions. The clay suspension completely killed acid-sensitive and acid-tolerant E. coli O157:H7 strains, whereas incubation in a low-pH buffer resulted in a minimal decrease in viability, demonstrating that low pH alone does not mediate antibacterial activity. The prevailing hypothesis is that metal ions participate in redox cycling and produce ROS, leading to oxidative damage to macromolecules and resulting in cellular death. However, E. coli cells showed no increase in DNA or protein oxidative lesions and a slight increase in lipid peroxidation following exposure to the antibacterial leachate. Further, supplementation with numerous ROS scavengers eliminated lipid peroxidation, but did not rescue the cells from CB-L-mediated killing. In contrast, supplementing CB-L with EDTA, a broad-spectrum metal chelator, reduced killing. Finally, CB-L was equally lethal to cells in an anoxic environment as compared to the aerobic environment. Thus, ROS were not required for lethal activity and did not contribute to toxicity of CB-L. We conclude that clay-mediated killing was not due to oxidative damage, but rather, was due to toxicity associated directly with released metal ions.
从天然抗菌粘土制备的水浸出液(任意命名为CB-L)会将金属离子释放到悬浮液中,pH值较低(3.4 - 5),会产生活性氧(ROS)和H2O2,并且具有较高的氧化还原电位。为了分离pH值在CB粘土混合物抗菌活性中的作用,我们将三种不同的大肠杆菌O157:H7菌株暴露于10%的粘土悬浮液中。粘土悬浮液完全杀死了对酸敏感和耐酸的大肠杆菌O157:H7菌株,而在低pH缓冲液中孵育只会导致活力轻微下降,这表明仅低pH值并不能介导抗菌活性。目前普遍的假设是金属离子参与氧化还原循环并产生活性氧,导致对大分子的氧化损伤并导致细胞死亡。然而,大肠杆菌细胞在暴露于抗菌浸出液后,DNA或蛋白质的氧化损伤没有增加,脂质过氧化略有增加。此外,添加多种活性氧清除剂消除了脂质过氧化,但并没有使细胞免受CB-L介导的杀伤。相反,用广谱金属螯合剂EDTA补充CB-L可降低杀伤作用。最后,与有氧环境相比,CB-L在缺氧环境中对细胞同样具有致死性。因此,致死活性不需要活性氧,活性氧也不会导致CB-L的毒性。我们得出结论,粘土介导的杀伤不是由于氧化损伤,而是由于与释放的金属离子直接相关的毒性。