Iron piracy: acquisition of transferrin‐bound iron by bacterial pathogens

Abstract

The mechanism of iron utilization from transferrin has been most extensively characterized in the pathogenic Neisseria species and Haemophilus species. Two transferrin-binding proteins, Tbp1 and Tbp2, have been identified in these pathogens and are thought to be components of the transferrin receptor. Tbp1 appears to be an integral, TonB-dependent outer membrane protein while Tbp2, a lipoprotein, may be peripherally associated with the outer membrane. The relative contribution of each of these proteins to transferrin binding and utilization is discussed and a model of iron uptake from transferrin is presented. Sequence comparisons of the genes encoding neisserial transferrin-binding proteins suggest that they are probably under positive selection for variation and may have resulted from inter-species genetic exchange.

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

“…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and Morris, 1988b;Pettersson et al, 1993;1994a,b;Biswas and Sparling, 1995;Bonnah et al, 1995;Lewis et al, 1996;our unpublished observations).…”

Heme uptake across the outer membrane as revealed by crystal structures of the receptor–hemophore complex

“…Bacteria can also use iron sources other than ferrisiderophores such as iron carried by ferriproteins [transferrin (2) or lactoferrin (3)], heme, hemoproteins (4) (hemoglobin, hemopexin, etc. ), and hemophores (small bacterial extracellular proteins that scavenge heme owing to their very high affinity) (5,6).…”

Identification of a conserved Moraxella catarrhalis haemoglobin-utilization protein, MhuA

“…These two specific receptor systems are similar in composition, with an integral outermembrane protein (OMP) component and an outermembrane lipoprotein component that work together to bind the iron-carrier protein and internalize the iron moiety. These well-known transferrin-and lactoferrinbinding systems have been described for many other pathogens, including pathogenic species of the genera Neisseria and Haemophilus (Cornelissen & Sparling, 1994;Gray-Owen & Schryvers, 1996;Schryvers, 1989). Investigators have provided evidence that these surface receptors have vaccine potential, although significant heterogeneity has been reported (Ala 'Aldeen & Borriello, 1996;Ala'Aldeen et al, 1994;Johnson et al, 1999;Masri & Cornelissen, 2002;Rokbi et al, 2000;West et al, 2001).…”