9.A.83.  The FezAB Iron Transporter (FezAB) Family 

Iron is indispensable for almost all forms of life but toxic at elevated levels. 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. Pi et al. 2023 reported that C. difficile undergoes an intracellular iron biomineralization process and stores iron in membrane-bound ferrosome organelles containing non-crystalline iron phosphate biominerals. They found that a membrane protein (FezA) and a P1B6-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.



Pi, H., R. Sun, J.R. McBride, A.R.S. Kruse, K.N. Gibson-Corley, E.S. Krystofiak, M.R. Nicholson, J.M. Spraggins, Q. Zhou, and E.P. Skaar. (2023). Clostridioides difficile ferrosome organelles combat nutritional immunity. Nature. [Epub: Ahead of Print]


TC#NameOrganismal TypeExample

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 with highest similarity in TCDB to the protein with TC# 3.A.3.32.1 (53% identity) (Pi et al. 2023). FezB has 699 aas and may have as many as 10 TMSs.  However, all member of TC family 3.A.3.32 are predicted to have fewer than 10 TMSs.  The function identified for this protein indicates that all members of subfamily 3.A.3.32 may transport iron, probably in the ferric iron valency.

FezAB of Clostridioides difficile