Microbial cellular redox and signal transduction pathways

Microbial cellular redox and signal transduction pathways represent a complex network of systems, such as the thioredoxin and glutathione systems, that maintain the intracellular reduction-oxidation balance essential for survival (Lu & Holmgren, 2014; PMID: 24412293). These pathways also include two-component systems (TCS), which consist of a sensor histidine kinase and a response regulator, allowing microbes to sense and respond to environmental changes (Stock et al., 2000; PMID: 10838337). In pathogenic microbes, these systems are vital for adapting to host-induced oxidative stress and regulating the expression of virulence factors (Teixeira et al., 2014; PMID: 24782841). Therapeutic strategies targeting these pathways often involve the use of prodrugs like metronidazole, which are activated by microbial redox enzymes to form toxic intermediates, or inhibitors like auranofin that target specific enzymes like thioredoxin reductase (Harbut et al., 2015; PMID: 25938274). Because this term describes a broad set of biological processes and multiple distinct protein families rather than a single molecular entity, it is classified as a pathway group rather than a discrete therapeutic target. Disruption of these pathways is a key mechanism for several antimicrobial agents, though achieving selectivity remains a challenge due to the presence of analogous redox systems in human mitochondria (Ezraty et al., 2017; PMID: 28435154).

Other names

Microbial redox systemsBacterial signal transductionTwo-component systems and redox homeostasisMicrobial antioxidant defense systems

Drugs targeting these pathways typically act through the generation of reactive oxygen species (ROS), inhibition of antioxidant enzymes such as thioredoxin reductase, or the disruption of phosphorylation-dependent signaling in two-component systems.