Bacterial iron acquisition mediated by outer membrane translocation and cleavage of a host protein

• Published in: Proceedings of the National Academy of Sciences - PNAS 2018-06, Vol.115 (26), p.6840-6845
• Main Authors: Mosbahi, Khedidja, Wojnowska, Marta, Albalat, Amaya, Walker, Daniel
• Format: Article
• Language: English
• Subjects: ABC transporter; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biological Sciences; Cell Membrane - genetics; Cell Membrane - metabolism; Cell surface; Chelation; Chloroplasts; Cleavage; Cytoplasm; Ferredoxin; Gram-negative bacteria; Homology; Iron; Iron - metabolism; Membrane proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membranes; Mitochondria; Nutrient uptake; Pectobacterium; Pectobacterium - genetics; Pectobacterium - metabolism; Peptide Elongation Factor G - genetics; Peptide Elongation Factor G - metabolism; Periplasm; Periplasm - genetics; Periplasm - metabolism; Proteases; Protein transport; Proteins; Proteolysis; Siderophores; Sulfur; Translocation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1800672115

Iron is an essential micronutrient for most bacteria and is obtained from iron-chelating siderophores or directly from iron-containing host proteins. For Gram-negative bacteria, classical iron transport systems consist of an outer membrane receptor, a periplasmic binding protein, and an inner membrane ABC transporter, which work in concert to deliver iron from the cell surface to the cytoplasm. We recently showed that Pectobacterium spp. are able to acquire iron from ferredoxin, a small and stable 2Fe-2S iron sulfur cluster containing protein and identified the ferredoxin receptor, FusA, a TonB-dependent receptor that binds ferredoxin on the cell surface. The genetic context of fusA suggests an atypical iron acquisition system, lacking a periplasmic binding protein, although the mechanism through which iron is extracted from the captured ferredoxin has remained unknown. Here we show that FusC, an M16 family protease, displays a highly targeted proteolytic activity against plant ferredoxin, and that growth enhancement of Pectobacterium due to iron acquisition from ferredoxin is FusC-dependent. The periplasmic location of FusC indicates a mechanism in which ferredoxin is imported into the periplasm via FusA before cleavage by FusC, as confirmed by the uptake and accumulation of ferredoxin in the periplasm in a strain lacking fusC. The existence of homologous uptake systems in a range of pathogenic bacteria suggests that protein uptake for nutrient acquisition may be widespread in bacteria and shows that, similar to their endosymbiotic descendants mitochondria and chloroplasts, bacteria produce dedicated protein import systems.