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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.

References associated with 9.A.83 family:

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] 37968387