Physiology and metabolism of Neisseria gonorrhoeae and Neisseria meningitidis: implications for pathogenesis

Abstract

Gonococci and meningococci are obligate human pathogens that can infect diverse sites within the human host. Each of these sites represents a unique niche with respect to nutrients, environmental factors, and competing microorganisms. The growth environment has a marked effect on the metabolism and cellular composition of Neisseria gonorrhoeae and N. meningitidis. Altered cellular composition is often reflected by changes in the cell surface that can ultimately affect the interaction of these microorganisms with the human host. The physiology and metabolism of the pathogenic Neisseria spp. have not been reviewed since 1979 (41). This review will discuss selected areas that have implications for the pathogenesis of these important microorganisms. IRON METABOLISMAfter entry into the human host, N. gonorrhoeae and N. meningitidis must multiply to colonize mucosal surfaces and to establish an infection. Cell growth and multiplication require essential nutrients such as iron. To obtain iron, the pathogenic Neisseria spp. must acquire it from the host. Despite the relative abundance of iron in the host, there is little free iron because of its sequestration by the ironbinding proteins transferrin (TF) and lactoferrin (LF) (19). In serum and interstitial fluid, iron is associated with TF; in breast milk, semen, and mucosal surfaces, it is associated primarily with LF. Consequently, gonococci and meningococci must possess mechanisms for utilizing the iron associated with the host iron-binding proteins as well as other potential in vivo iron sources such as heme and hemoglobin.Several studies have implicated iron in the virulence of the pathogenic Neisseria spp. Calver et al. (7) demonstrated that injection of ferrous sulfate prior to or injection of either iron sorbitol citrate or iron-dextran concomitantly with injection of N. meningitidis increased the lethality of several different meningococcal serogroups for mice by up to a 106-fold. The effect of the added iron was partially abrogated by the prior incubation of N. meningitidis with Desferal (CIBA-GEIGY Corp.), an iron chelator from which meningococci and gonococci are unable to remove iron (36). Holbein et al. (24) showed that the 50% lethal dose of N. meningitidis strains in a mouse model was decreased 109-fold by the concomitant administration of iron-dextran with the inoculum. Payne and Finkelstein (50) found that the intravenous inoculation of iron-containing compounds together with avirulent (nonpiliated) gonococci increased the lethality of these avirulent organisms for chicken embryos.Hafiz et al. (20) All strains of N. gonorrhoeae and N. meningitidis are able to grow with 25% iron-saturated TF as their sole source of iron (37). Archibald and DeVoe (1, 2) found that meningococci were capable of obtaining iron from a variety of iron-containing compounds including gastric mucin, ferric citrate, hemoglobin, myoglobin, and human TF. Iron complexed with a number of metabolic organic acids, polyphosphates, and several synthetic polycarboxylic acids was also re...

Iron acquisition and the pathogenesis of meningococcal and gonococcal disease

“…Gonococcal mutants deficient in the uptake of Tf-bound iron are avirulent in the mouse subcutaneous chamber model [12]. Only fragmentary data are presently available on how iron might regulate its own uptake and the virulence of the pathogenic Neisseriae.…”

“…From here the iron is transported into the cytoplasm [36]. Recently, a second sophisticated system for iron acquisition has been identified which seems to be unique to strictly human mucosal pathogens, such as the pathogenic Neisseriae [12,13], Haemophilus influenzae [46] and Bordetella pertussis [44]. Evidence is growing that this mechanism has a central position in the growth and virulence of these organisms in vivo, and that it might serve as a useful target in vaccine development.…”

Fur-Mediated Global Regulatory Circuits in Pathogenic Neisseria Species

“…However, one of the differences between speciesspecific host niches is the iron source. In serum, transferrin is the major iron-carrying protein, while in the mucosal surfaces, lactoferrin is the major iron source (14). In addition, the concentration of lactoferrin can change with the menstrual cycle in human vaginal mucus (15).…”

Effect of atorvastatin on diabetic rat endothelial cells and retinal lesions

“…The pathogenesis of DR is unclear. Traditionally, DR was thought to be caused by numerous factors, while modern research suggests that DR is caused by changes in multiple factors, such as blood glucose, blood fat, glycosylated hemoglobin, retinal blood dynamics, and hemorheology, leading to bloodretinal barrier damage and retinal neovascularization (Chen et al, 1989;He et al, 2013).…”