Anaerobic electron-transport proteins

Anaerobic electron-transport proteins, such as ferredoxin and pyruvate:ferredoxin oxidoreductase (PFOR), are critical components of the metabolic pathways in obligate anaerobic bacteria and certain protozoa [1, 8, 16]. These proteins are characterized by their exceptionally low redox potential, which allows them to facilitate electron transfer during anaerobic respiration and fermentation processes [2, 4, 15]. In clinical pharmacology, they serve as the primary mediators for the activation of nitroimidazole prodrugs like metronidazole [1, 6, 11]. Within the anaerobic environment of the pathogen, these proteins reduce the drug's nitro group to form highly reactive, short-lived nitro radical anions [4, 8, 13]. These radicals interact with and damage microbial DNA, leading to strand breaks and the inhibition of nucleic acid synthesis, which results in cell death [2, 5, 14]. The absence of these specific low-redox-potential proteins in aerobic organisms and human cells provides the basis for the selective toxicity of these antimicrobial agents [9, 18]. Resistance to these drugs often involves mutations that decrease the expression or activity of these electron-transport components [14, 16]. Understanding these proteins is essential for managing infections caused by pathogens like Bacteroides fragilis, Clostridioides difficile, and Trichomonas vaginalis [1, 18]. Therapeutic challenges include the potential for neurotoxicity and the development of multidrug-resistant anaerobic strains [9, 14]. Overall, these proteins represent a unique metabolic vulnerability in anaerobes that is successfully exploited by current antimicrobial therapies [11, 18].

Other names

Electron-transport proteins in anaerobic organismsFerredoxinFlavodoxinPyruvate:ferredoxin oxidoreductasePFORNitroreductaseAnaerobic electron transport proteins

Reductive activation of nitroimidazole prodrugs into cytotoxic free radicals that damage DNA and inhibit nucleic acid synthesis.