Reduce, Induce, Thrive: Bacterial Redox Sensing during Pathogenesis

Abstract

The abundance of oxidants and reductants must be balanced for an organism to thrive. Bacteria have evolved methods to prevent redox imbalances and to mitigate their deleterious consequences through the expression of detoxification enzymes, antioxidants, and systems to repair or degrade damaged proteins and DNA. Regulating these processes in response to redox changes requires sophisticated surveillance strategies ranging from metal chelation to direct sensing of toxic reactive oxygen species. In the case of bacterial pathogens, stress that threatens to disrupt redox homeostasis can derive from endogenous sources (produced by the bacteria) or exogenous sources (produced by the host). This minireview summarizes the sources of redox stress encountered during infection, the mechanisms by which bacterial pathogens diminish the damaging effects of redox stress, and the clever ways some organisms have evolved to thrive in the face of redox challenges during infection.

Keywords: RNS; ROS; bacillithiol; glutathione; iron; iron regulation; low-molecular-weight thiols; metabolism; mycothiol; pathogenesis; phagocytosis; regulation; virulence; virulence regulation.

FIG 1

Host defense mechanisms against intracellular bacterial pathogens. (A) Host-derived antimicrobial ROS and RNS (highlighted in yellow). Host proteins are in blue boxes, and bacterial detoxification enzymes are in red boxes. NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS) are recruited to the phagosome in the respiratory burst. Myeloperoxide (MPO) is a significant component of neutrophil granules but is also found in phagolysosomes (97). Superoxide dismutase (SOD), catalase (Kat), and peroxiredoxins (Prx) detoxify ROS, while flavohemoglobin (Hmp) and flavorubredoxin (NorV) detoxify RNS. At low pH, peroxynitrite will be protonated (ONOOH [24]). Similarly, superoxide is protonated in the phagolysosome to form the reactive HO₂˙ species (13). (B) Simplified schematic depicting macrophage phagosomal maturation (97). The pH of the phagosome steadily decreases, according to the pH scale shown, via recruitment of the vacuolar ATPase (vATPase). The bacterium is in gray. Not drawn to scale.