Sense and sensor ability: redox-responsive regulators in Listeria monocytogenes

Abstract

Listeria monocytogenes is a Gram-positive bacterium that thrives in nature as a saprophyte and in the mammalian host as an intracellular pathogen. Both environments pose potential danger in the form of redox stress. In addition, endogenous reactive oxygen species (ROS) are continuously generated as by-products of aerobic metabolism. Redox stress from ROS can damage proteins, lipids, and DNA, making it highly advantageous for bacteria to evolve mechanisms to sense and detoxify ROS. This review focuses on the five redox-responsive regulators in Lm: OhrR (to sense organic hydroperoxides), PerR (peroxides), Rex (NAD + /NADH homeostasis), SpxA1/2 (disulfide stress), and PrfA (redox stress during infection).

Stimulating Respiratory Activity Primes Anaerobically Grown Listeria monocytogenes for Subsequent Intracellular Infections

“…Moreover, the oncogenic effects of fumarate accumulated in FH-deficient cells have helped introduce fumarate as a potential oncometabolite [22]. Elevated levels of fumarate in FH-deficient cells also lead to succination of glutathione, resulting in increased production of reactive oxygen species [23] and defects in respiratory chain activities [24]—both processes may implicate the outcome of L. monocytogenes infections [25,26]. Whether exogenous fumarate supplementation to fibroblasts in our experimental design leads to an increase in cytosolic fumarate or similar responses in ROS production or mitochondrial functions is not clear.…”

YjbH mediates the oxidative stress response and infection by regulating SpxA1 and the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) in Listeria monocytogenes

“…37 The intracellular lifecycle of Listeria requires it to survive the harsh phagosomal compartment, escape into the highly reducing cytosol, and spread to neighboring cells. 12 Proteins in the thioredoxin family play major roles in the protection of cells against toxic oxygen species as well as maintaining the bacterial thiol-disulfide balance. Here, we investigated the roles of thioredoxin-like YjbH in the adaptation of L. monocytogenes to diverse redox environments and, more importantly, in the regulation of PTS and virulence during infection.…”

“…In B. subtilis, oxidized Spx activates >100 redox homeostasis genes (e.g., thioredoxin, bacillithiol biosynthesis, and oxidoreductase genes), and represses approximately 170 genes involved in energy-consuming functions. 12,24,45 Among these Spx-regulated genes, the beta-glucoside-and mannose-specific PTS components, enzyme II ABC, are directly regulated by Spx. 45 Thus, we speculate that PTS regulation in L. monocytogenes is YjbHdependent under oxidative conditions, and this regulation switches to become YjbH independent when the stress is relieved.…”

“…10 Therefore, L. monocytogenes is an excellent model system for studying bacterial adaptive responses to redox changes during host infection. 11,12 Bacteria maintain the cytosolic redox status largely by using redox-regulating thiol molecules such as glutathione and the dicysteine proteins thioredoxin and glutaredoxin. 13 At the expense of NADPH, glutathione is maintained in a reduced state by glutathione reductase, and thioredoxin is kept reduced by thioredoxin reductase.…”

“…This enables activation of >140 genes and operons to help reestablish the cytoplasmic thiol-disulfide redox balance and repair the stress-related damage. 12,28 L. monocytogenes encodes two Spx paralogs, SpxA1 and SpxA2, and SpxA1 but not SpxA2 is required for resistance to oxidative stress and pathogenesis, suggesting a critical role for SpxA1 in redox homeostasis and virulence. 5,11 However, the interactive relationships and underlying mechanisms of SpxA1-YjbH remain unclear.…”