3.A.3.32.10
FezAB iron transport system where FezA is a membrane protein with 131 aas and 1 N-terminal TMS, and FezB is an ATPase of the P-type ATPase family (Pi et al. 2023). FezB has 699 aas and may have 8 TMSs. The function identified for this protein indicates that other members of subfamily 3.A.3.32 may transport ferric iron (Pi et al. 2023). To survive within their hosts, bacterial pathogens have evolved iron uptake, storage and detoxification strategies to maintain iron homeostasis. Three Gram-negative environmental anaerobes produce iron-containing ferrosome granules. The Gram-positive bacterium Clostridioides difficile is the leading cause of nosocomial and antibiotic-associated infections in the USA. C. difficile undergoes an intracellular iron biomineralization process and stores iron in membrane-bound ferrosome organelles containing non-crystalline iron phosphate biominerals. FezA and a P_1B6-ATPase transporter (FezB), repressed by both iron and the ferric uptake regulator, Fur, are required for ferrosome formation and play an important role in iron homeostasis during transition from iron deficiency to excess. Ferrosomes are often localized adjacent to cellular membranes as shown by cryo-electron tomography. Using two mouse models of C. difficile infection, Pi et al. 2023 demonstrated that the ferrosome system is activated in the inflamed gut to combat calprotectin-mediated iron sequestration and is important for bacterial colonization and survival during C. difficile infection.