Subversion of nutritional immunity by the pathogenic Neisseriae

Abstract

The pathogenic Neisseria species, including Neisseria meningitidis and Neisseria gonorrhoeae, are obligate human pathogens that cause significant morbidity and mortality. The success of these pathogens, with regard to causing disease in humans, is inextricably linked to their ability to acquire necessary nutrients in the hostile environment of the host. Humans deploy a significant arsenal of weaponry to defend against bacterial pathogens, not least of which are the metal-sequestering proteins that entrap and withhold transition metals, including iron, zinc and manganese, from invaders. This review will discuss the general strategies that bacteria employ to overcome these metal-sequestering attempts by the host, and then will focus on the relatively uncommon 'metal piracy' approaches utilized by the pathogenic Neisseria for this purpose. Because acquiring metals from the environment is critical to microbial survival, interfering with this process could impede growth and therefore disease initiation or progression. This review will also discuss how interfering with metal uptake by the pathogenic Neisseriae could be deployed in the development of novel or improved preventative or therapeutic measures against these important pathogens.

Aggregatibacter Actinomycetemcomitans: Clinical Significance of a Pathobiont Subjected to Ample Changes in Classification and Nomenclature

“…Iron is an essential transition metal for nearly all forms of life. The host limits the availability of iron through a process termed nutritional immunity [92]. Haemolysis can be an initial step for release of iron from heme by Gram-negative bacteria.…”

The Diversity of Mammalian Hemoproteins and Microbial Heme Scavengers Is Shaped by an Arms Race for Iron Piracy

“…In fact, most gonococcal strains isolated from human patients are phase off for HpuA/B with the exclusion of those deriving from women in their early menses ( 94 ). Moreover, N. gonorrhoeae strains isolated to date do not express HmbR, which is present as a frame-shifted pseudogene ( 95 ). Overall, these observations suggest that gonococci are less dependent on Hb as an iron source than meningococci and thus that the selective pressure acting on HpuA/B is weak in N. gonorrhoeae .…”

The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae

“…In experimental murine infection, Ng is seen adherent to vaginal epithelial cells, in cervical tissue and within the lamina propria, which is presumably mediated by other Ng colonization ligands for which species specificity has not been defined [45, 46] or that are not host-restricted [47]. Acquisition of iron from lactoferrin (LF) and transferrin (TF), and recently, zinc from calprotectin [48], is also host-restricted. These restrictions limit the ability to fully evaluate the efficacy of vaccines that induce antibodies that block colonization or nutrient uptake in the mouse model, although mice that are transgenic for the human carcinoemybryonic antigen cellular adherence molecules (CEACAMs), the major Opa protein receptors and hTF could be used [49-51].…”