β-Lactam Exposure Triggers Reactive Oxygen Species Formation in Enterococcus faecalis via the Respiratory Chain Component DMK

• Main Authors: Loïc Léger, Aurélie Budin-Verneuil, Margherita Cacaci, Abdellah Benachour, Axel Hartke, Nicolas Verneuil
• Format: Article
• Language: English
• Published: Elsevier 2019-11-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124719314020

Summary: 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. : Léger et al. show that β-lactams treatment enhances superoxide and hydrogen peroxide production in Enterococcus faecalis in a mainly demethylmenaquinone (DMK)-dependent process. In the absence of respiration, the antibiotics trigger the accumulation of the reduced form of DMK, a respiratory chain component, which increases the adventitious reactivity with oxygen. Keywords: Enterococcus, β-lactams, oxidative stress, ROS, respiratory chain