UR Risques Microbiens, Normandie Univ, UNICAEN, U2RM, 14000 Caen, France.
Università Cattolica del Sacro Cuore, Instituto di Microbiologia, Rome, Italy.
Cell Rep. 2019 Nov 19;29(8):2184-2191.e3. doi: 10.1016/j.celrep.2019.10.080.
Whereas the primary actions of β-lactams are well characterized, their downstream effects are less well understood. Although their targets are extracellular, β-lactams stimulate respiration in Escherichia coli leading to increased intracellular accumulation of reactive oxygen species (ROS). Here, we show that β-lactams over a large concentration range trigger a strong increase in ROS production in Enterococcus faecalis under aerobic, but not anaerobic, conditions. Both amoxicillin, to which the bacterium is susceptible, and cefotaxime, to which E. faecalis is resistant, triggers this response. This stimulation of ROS formation depends mainly on demethylmenaquinone (DMK), a component of the E. faecalis respiratory chain, but in contrast to E. coli is observed only in the absence of respiration. Our results suggest that in E. faecalis, β-lactams increase electron flux through the respiratory chain, thereby stimulating the auto-oxidation of reduced DMK in the absence of respiration, which triggers increased extracellular ROS production.
β-内酰胺类抗生素的主要作用已得到充分描述，但它们的下游效应则知之甚少。尽管它们的靶标在细胞外，但β-内酰胺类抗生素会刺激大肠杆菌的呼吸，导致活性氧（ROS）在细胞内的积累增加。在这里，我们发现在有氧但不是厌氧条件下，β-内酰胺类抗生素在很大的浓度范围内都会引发粪肠球菌中 ROS 产生的强烈增加。对细菌敏感的阿莫西林和粪肠球菌耐药的头孢噻肟都能触发这种反应。这种 ROS 形成的刺激主要依赖于甲基萘醌（DMK），DMK 是粪肠球菌呼吸链的一个组成部分，但与大肠杆菌不同的是，这种刺激只有在没有呼吸的情况下才会观察到。我们的结果表明，在粪肠球菌中，β-内酰胺类抗生素增加了电子通过呼吸链的流动，从而刺激了在没有呼吸的情况下还原 DMK 的自动氧化，这触发了细胞外 ROS 产生的增加。
