Gonococcal transferrin-binding protein 1 is required for transferrin utilization and is homologous to TonB-dependent outer membrane receptors

Abstract

The pathogenic Neisseria species are capable of utilizing transferrin as their sole source of iron. A neisserial transferrin receptor has been identified and its characteristics defined; however, the biochemical identities of proteins which are required for transferrin receptor function have not yet been determined. We The ability of many human pathogens to cause infection is dependent in part on their ability to acquire iron from their host. Unlike the members of the family Enterobacteriaceae, the pathogenic Neisseria species do not produce and secrete soluble siderophores to compete with host iron-binding proteins such as transferrin (Tf) and lactoferrin (Lf), but instead can acquire iron directly from these proteins (32, 33). Utilization requires direct contact between Tf and the cell membrane (1,30,53), which implies the presence of specific receptors for these iron-binding proteins. Recent evidence suggests that other human pathogens such as Haemophilus influenzae and Bordetella pertussis also possess specific receptors for Tf (43,48).Tf receptor function has been characterized in the pathogenic Neisseria species (8,27,50,58). Tf utilization and binding is iron repressible (27,50,53,60)

Cloning and functional characterization of Neisseria gonorrhoeae tonB, exbB and exbD genes

“…Tbp1 (Cornelissen et al, 1992;Legrain et al, 1993), Lbp1 (lbpA product) (Pettersson et al, 1993;Biswas and Sparling, 1995) and HpuB (Roe et al, 1996) each exhibit extensive similarity to TonB-dependent receptors in Gram-negative bacteria. HmbR also exhibits similarities to TonB-dependent receptors (Stojiljkovic et al, 1995).…”

“…The TF receptor is composed of the 100 kDa transmembrane protein, Tbp1, and the 85 kDa lipoprotein, Tbp2, encoded by the genes tbpA and tbpB, respectively (Schryvers and Morris, 1988a;Cornelissen et al, 1992;Legrain et al, 1993;Anderson et al, 1994;Cornelissen and Sparling, 1994;Cornelissen and Sparling, 1996). The LF receptor is composed of the 103 kDa transmembrane protein Lbp1 and a lipoprotein, Lbp2, analogous to Tbp2 encoded by the genes lbpA and lbpB, respectively (Schryvers and Morris, 1988b;Pettersson et al, 1993;1994a,b;Biswas and Sparling, 1995;Bonnah et al, 1995;Lewis et al, 1996;our unpublished observations).…”

The proline‐rich domain of TonB possesses an extended polyproline II‐like conformation of sufficient length to span the periplasm of Gram‐negative bacteria

“…2 The TonB system is also critical for uptake of bacterial toxins like colicin Ia and B 3 and certain antibiotics (albomycin, rifamycin, and microcin 25 4 ). In complex with the cytoplasmic membrane proteins ExbB and ExbD, and dependent on the proton motive force, TonB serves a large class of ''TonB-dependent'' outer membrane receptors, each responsible for the uptake of specific cargo molecules, including iron complexed by siderophores, heme, 5 transferrin 6 and lactoferrin, cobalt as cyanocobalamin, nickel, copper, thiamine, and carbohydrates. 7 In the cell, these receptors outnumber TonB.…”

Transferrin Binding Proteins as a Means to Obtain Iron in Parasitic Protozoa

“…TbpA is similar to a classical receptor; it is an integral membrane protein that depends on TonB for energy transduction between the OM and IM. TbpA transports ferric ions across the OM [Cornelissen et al, 1992]. TbpB is a surface-exposed lipoprotein that binds TF independently [Gray-Owen and Schryvers, 1995].…”