The fbpABC locus of Neisseria gonorrhoeae functions in the periplasm-to-cytosol transport of iron

Abstract

We have determined that the DNA sequence downstream of the well-characterized gonococcal fbp gene contains two open reading frames: one designated fbpB, which encodes a protein proposed to function as a cytoplasmic permease, and one designated fbpC, which encodes a protein proposed to function as a nucleotidebinding protein. The fpbABC operon composes an iron transport system that is homologous to the sfu and hit operons previously reported for Serratia marcescens and Haemophilus influenzae, respectively, and displays elements characteristic of ATP binding cassette transporters. The fpbABC operon differs from these loci in that it is lethal when overexpressed in Escherichia coli.

Sulfate as a Synergistic Anion Facilitating Iron Binding by the Bacterial Transferrin FbpA: The Origins and Effects of Anion Promiscuity

“…12,13 In these cases, a single periplasmic iron-binding protein, ferric binding protein (FbpA), designated hFbpA (HitA) in Haemophilus influenzae and nFbpA (FbpA) in Neisseria gonorrhoeae 14 effectively mediates iron transport from the inside of the outer membrane to the outside of the inner membrane. 3,5,[16][17][18][19] As the only means of shuttling iron across the periplasmic space, FbpA plays a pivotal role in the iron uptake process of these pathogens, perhaps as the rate-limiting step in bacterial iron acquisition .3 FbpA is a member of the transferrin superfamily of proteins that traces its ancestry to an anion binding protein. 20 FbpA is referred to as bacterial transferrin; a title attributed to both functional and structural similarities to mammalian transferrin.…”

Characterization of a Nucleotide-Binding Domain Associated with Neisserial Iron Transport

“…Iron is removed from these host iron-binding proteins and transferred to the periplasmic iron-binding protein FbpA (ferric iron-binding protein), which initiates the periplasm-to-cytosol transport of iron. Adhikari et al (1996) determined the nucleotide sequence of the fbpABC operon in N. gonorrhoeae (1) and proposed that these three genes encode a periplasmic binding protein, cytoplasmic permease, and a nucleotide-binding domain, respectively. The addition of a plasmid containing the fbpABC operon enables siderophore-deficient Escherichia coli strains to grow on nutrient agar containing an inhibitory concentration of 2,2Ј-dipyridyl, an iron chelator, showing that this operon functions as an iron transport system at the periplasmto-cytosol level (1).…”

“…Adhikari et al (1996) determined the nucleotide sequence of the fbpABC operon in N. gonorrhoeae (1) and proposed that these three genes encode a periplasmic binding protein, cytoplasmic permease, and a nucleotide-binding domain, respectively. The addition of a plasmid containing the fbpABC operon enables siderophore-deficient Escherichia coli strains to grow on nutrient agar containing an inhibitory concentration of 2,2Ј-dipyridyl, an iron chelator, showing that this operon functions as an iron transport system at the periplasmto-cytosol level (1). Initial attempts to detect the expression of FbpB (511 amino acids) and FbpC (352 amino acids) in ironstressed N. gonorrhoeae or in E. coli constructs containing the fbpABC operon have been unsuccessful (1,21).…”

“…The addition of a plasmid containing the fbpABC operon enables siderophore-deficient Escherichia coli strains to grow on nutrient agar containing an inhibitory concentration of 2,2Ј-dipyridyl, an iron chelator, showing that this operon functions as an iron transport system at the periplasmto-cytosol level (1). Initial attempts to detect the expression of FbpB (511 amino acids) and FbpC (352 amino acids) in ironstressed N. gonorrhoeae or in E. coli constructs containing the fbpABC operon have been unsuccessful (1,21). However, Khun and coworkers recently showed the presence of fbpAB and fbpBC transcripts in Neisseria meningitidis by reverse transcription-PCR, suggesting that the fbpABC locus is transcribed as a single contiguous message in that organism (9).…”

“…Interestingly, reconstitution of the wild-type genotype by replacing the mutated hitC gene with the wild-type allele by allelic exchange created a new strain that was able to utilize all of these iron sources (18), indicating the critical role of HitC in the iron transport process. Moreover, reverse transcription-PCR of the fbpABC locus in N. meningitidis detected an fbpC transcript (9); in contrast, no fbpC transcripts were detected in RNA samples from N. gonorrhoeae cultures (1,21). Detection of fbpBC transcripts implies a functional role for FbpB and FbpC in neisserial periplasmic iron transport.…”