Mechanisms of iron acquisition by the human pathogens Neisseria meningitidis and Neisseria gonorrhoeae.

Abstract

It is well established that bacterial pathogenesis is dependent on the ability to acquire iron within the host. The success of the highly adapted obligate human pathogens Neisseria meningitidis (NM) and Neisseria gonorrhoeae (NG) can be attributed in part to the efficient utilization of multiple host iron (Fe) sources, allowing replication on mucosal surfaces, in the bloodstream, and intracellularly. Most Gram-negative bacterial strategies for scavenging iron from the human host rely on the TonB protein to energize active iron transport across the outer membrane. Pathogenic Neisseria express multiple high-affinity iron transporters including a family of two-component TonB-dependent receptors as well as multiple single-component TonB-dependent Fe transporters. This review describes our current understanding of the mechanisms Neisseria have evolved to utilize various iron sources encountered during infection of the human host. Recent studies have provided insight into the interaction of neisserial outer membrane receptors with host iron carrier proteins. Emerging structural information on neisserial iron transporters will be compared with the crystal structures and biochemical data available for homologous Escherichia coli TonB-dependent Fe-siderophore receptors. In the process, we will highlight the aspects of the iron transport process that are unique and those that remain to be experimentally demonstrated in Neisseria. These include receptor structure/function, the mechanism of iron removal from protein ligands, the fate of Fe and heme-Fe after traversing the outer membrane, and the role of TonB-associated energy in receptor functions. Finally, we will discuss regulatory mechanisms that control the expression of iron scavenging systems. The investigation of iron metabolism in NM and NG is important for understanding the biochemistry of this virulence factor, the development of vaccines targeted at outer membrane iron receptors, and therapeutic interventions exploiting these transporters as high affinity drug delivery systems.