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

Loïc Léger (1) , Aurélie Budin-Verneuil (2) , Margherita Cacaci (3) , Abdellah Benachour (2) , Axel Hartke (4) , Nicolas Verneuil (4)

1 UNICAEN - Université de Caen Normandie
2 U2RM - Unité de Recherche Risques Microbiens
3 Istituto di Microbiologia - Institute of Microbiology [Rome]
4 LME - Laboratoire de Microbiologie de l’Environnement

Whereas the primary actions of b-lactams are wellcharacterized, their downstream effects are lesswell understood. Although their targets are extracellular, b-lactams stimulate respiration in Escherichiacoli leading to increased intracellular accumulationof reactive oxygen species (ROS). Here, we showthat b-lactams over a large concentration rangetrigger a strong increase in ROS production inEnterococcus faecalis under aerobic, but not anaerobic, conditions. Both amoxicillin, to which the bacterium is susceptible, and cefotaxime, to whichE. faecalis is resistant, triggers this response. Thisstimulation of ROS formation depends mainly on demethylmenaquinone (DMK), a component of theE. faecalis respiratory chain, but in contrast toE. coli is observed only in the absence of respiration.Our results suggest that in E. faecalis, b-lactams increase electron flux through the respiratory chain,thereby stimulating the auto-oxidation of reducedDMK in the absence of respiration, which triggersincreased extracellular ROS production.

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology

Loïc Léger, Aurélie Budin-Verneuil, Margherita Cacaci, Abdellah Benachour, Axel Hartke, et al.. β-Lactam Exposure Triggers Reactive Oxygen Species Formation in Enterococcus faecalis via the Respiratory Chain Component DMK. Cell Reports, 2019, 29 (8), pp.2184-2191.e3. ⟨10.1016/j.celrep.2019.10.080⟩. ⟨hal-02371675⟩