Neisseria gonorrhoeae were exposed to extracts of human neutrophil granules and effects on gonococcal growth and membranes were determined. Enumeration of gonococci by phasecontrast microscopy at 0 and 60 min revealed that they underwent very limited cell division after exposure to granule extract. At 60 min, treated gonococci tended to clump, and some lost their refractivity under phase-contrast optics, indicating membrane damage. Treated and untreated gonococci utilized oxygen at similar rates at time 0; treated gonococci utilized oxygen at a relatively constant rate for 60 min, even though colony-forming ability (i.e. viability) decreased by 90 %, whereas untreated gonococci showed a steadily increasing rate of oxygen consumption over the same period, which essentially paralleled increase in colony-forming ability. Membrane ultrastructure of untreated and treated gonococci was compared in thin section by transmission electron microscopy. Extract treatment resulted in a time-related increase in disruption of the bacterial outer membrane, which became apparent almost immediately after treatment. This was accompanied by increasingly aberrant septum structure. Extract treatment also increased the resolution of peptidoglycan by electron microscopy, as early as 10 min after treatment. These data suggest that extract treatment of gonococci caused a rapid loss of the ability to form colonies on agar concomitant with alteration of gonococcal peptidoglycan and outer-membrane structure, but with little alteration of inner-membrane function.

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...