Enhancement of β-Lactam-Mediated Killing of Gram-Negative Bacteria by Lysine Hydrochloride

作者：Shouqiang Hong, Shaopeng Su, Qiong Gao, Miaomiao Chen, Lisheng Xiao, Runbo Cui, Yinli Guo, Yunxin Xue, Dai Wang, Jianjun Niu, Haihui Huang, Xilin Zhao · 发表于：Microbiology Spectrum · 年份：2023 · DOI：10.1128/spectrum.01198-23 · 被引用次数：10 · 研究领域：Antibiotic Resistance in Bacteria、Antibiotics Pharmacokinetics and Efficacy

Antibiotic resistance among Gram-negative pathogens is a serious medical problem. The present work describes a new study in which a nontoxic nutrient increases the lethal action of clinically important β-lactams. Elevated lethality is expected to reduce the emergence of resistant mutants. The effects were observed with significant pathogens (Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa), indicating widespread applicability. Examination of tolerant mutants and biochemical measurements revealed involvement of endogenous reactive oxygen species in response to outer membrane perturbation. These lysine hydrochloride-β-lactam data support the hypothesis that lethal stressors can stimulate the accumulation of ROS. Genetic and biochemical work also revealed how an alteration in a membrane protease, FtsH, abolishes lysine stimulation of β-lactam lethality. Overall, the work presents a method for antimicrobial enhancement that should be safe, easy to administer, and likely to apply to other nutrients, such as arginine.