Fumarate reductase (FRD) (FRD)

Fumarate reductase (FRD) is a membrane-bound enzyme complex in Helicobacter pylori that is essential for the bacterium's anaerobic respiration and energy metabolism [1, 3]. It catalyzes the reduction of fumarate to succinate, acting as the terminal electron acceptor in a non-cyclic Krebs cycle, which allows the pathogen to survive in the low-oxygen environment of the human gastric mucosa [1, 8]. While the enzyme is not strictly required for growth in vitro, it is indispensable for the colonization and persistence of H. pylori in the acidic stomach, as demonstrated in animal models [7]. Structurally, the complex consists of three subunits (FrdA, FrdB, and FrdC), with FrdA being highly immunogenic in infected patients [4, 6]. Targeting FRD is a promising therapeutic strategy, particularly for treating antibiotic-resistant strains, as its inhibition leads to a significant decrease in cellular ATP levels and bacterial death [1, 11]. Several drugs, including the proton pump inhibitor lansoprazole and anthelmintics such as oxantel and thiabendazole, have been identified as inhibitors of this enzyme [2, 13]. Because human cells utilize a related but functionally distinct enzyme (succinate dehydrogenase) for the reverse reaction, FRD represents a selective target for anti-infective drug development [1, 5].

Other names

Quinol:fumarate reductaseSuccinate dehydrogenase (fumarate reductase)FrdABC complexSuccinate:quinone oxidoreductase

Inhibition of the enzymatic reduction of fumarate to succinate, which disrupts the anaerobic respiratory chain and energy production (ATP synthesis) essential for bacterial survival and colonization [1, 11, 13].