U.S. Department of Health and Human Services

Bacterial Strategy To Acquire Iron from Humans

A three-dimensional reconstruction detailing the interactions between proteins from the bacteria Neisseria meningitidis and the human iron-binding protein transferrin has recently been determined. Two members of the Neisseria family of bacteria can cause disease in humans; one of these, N. meningitidis, is a leading cause of meningitis. It requires iron both for its survival and to cause disease. N. meningitidis collects iron by extracting it from the human transferrin receptor, a protein on the cell surface that binds to iron in the blood and transports it into cells. 

To acquire iron, the bacterium uses two proteins on its surface, TbpA and TbpB, that can bind to and remove iron from the transferrin receptor in the human host. The exact nature of this interaction is unknown. Determining the structure of these bacterial proteins and how they interact with host proteins is an important step in understanding how they function. 

Researchers have, for the first time in the laboratory, generated complexes of TbpA and TbpB bound to human transferrin that permitted the assembly of a three-dimensional reconstruction defining important interaction sites between the bacterial proteins and transferrin. They examined complexes of TbpA and transferrin, TbpB and transferrin, and of all three proteins together using three different methods. The reconstruction suggests a mechanism for bacterial uptake of iron, including how the bacteria latches on to transferrin, how a part of protein TbpA inserts itself into and displaces the iron from transferrin, and how the recently acquired iron is transported inside the bacteria. 
This study provides critical information regarding the structural basis for iron piracy by disease causing bacteria. Furthermore, as TbpA and TbpB are on the surface of the bacteria, this finding may have implications for the development of both structure based vaccines and drug design. 

Noinaj N, Easley NC, Oke M, et al. Structural basis for iron piracy by pathogenic Neisseria. Nature 483: 53-58, 2012.