Role of porin proteins in acquisition of transferrin iron by enteropathogens.

Acquisition of iron from key innate immune defence proteins such as transferrin (Tf) and lactoferrin is an important mechanism by which pathogenic bacteria obtain essential iron for growth within their host. Bacterial species that do not produce siderophores often use specific Tf-binding proteins, the best characterized being the Neisseriaceae-type Tf-binding proteins TbpA and TbpB. Previous work from our laboratory has shown that siderophore-producing enteric species such as Escherichia coli also readily bind Tf, although no genomic evidence exists for Tbp-like Tf-binding proteins. Application of proteomic analyses and molecular mutagenesis strategies to an enteropathogenic E. coli identified the OmpA and OmpC porins as Tf-binding proteins. Mutagenesis of the ompA or ompC genes affected E. coli Tf binding and, furthermore, compromised the ability of the ompA mutant to respond to growth promotion by certain catecholamine stress hormones. Evidence was also found to implicate the OmpA porin as an entry point for catecholamine stress hormones. Further proteomic analyses in other bacterial pathogens revealed wide-scale involvement of porins in Tf binding: Salmonella typhimurium (OmpC), and Shigella sonnei, Shigella flexneri and Shigella boydii (OmpC and/or OmpA). This study shows that in addition to their existing housekeeping functions, the Gram-negative porin family of proteins can also act as Tf-capture proteins for those bacteria that lack the classical Neisseriaceae-type Tf-binding proteins.