Carbon Unlike other
Neisseria species that can also metabolize maltose,
N. gonorrhoeae is capable of using only glucose, pyruvate, and lactate as central carbon sources, and glucose is catabolized via both the
Entner-Doudoroff (ED) and
pentose phosphate (PP) pathways, and the ED pathway is the primary oxidative method. Use of these pathways is necessary as
N. gonorrhoeae is incapable of glucose catabolism via the
Embden-Meyerhof-Parnas (EMP) pathway due its lack of the phosphofructokinase (PFK) gene; however, the fructose 1,6-bisphosphatase enzyme is present to allow for
gluconeogenesis to occur. The resultant pyruvate molecules are then converted into
acetyl-CoA, which can then be incorporated as a substrate for the
citric acid cycle (CAC) to yield high-energy electron carriers that will be used by the
electron transport chain (ETC) for ATP production; however, the CAC is largely used for generating biosynthetic precursors rather than for catabolic purposes. This is due in part to inhibited expression of several CAC enzymes in the presence of glucose, pyruvate, or lactate. These enzymes, namely
citrate synthase,
aconitase, and
isocitrate dehydrogenase, are needed for the incorporation of acetate. Instead, a partial CAC has been observed, where α-ketoglutarate is formed by
glutamate dehydrogenase or transamination of oxaloacetate and glutamate by
aspartate aminotransferase (yielding aspartate and α-ketoglutarate). While this acetate can enter the CAC for further oxidation, this does not occur so long as other carbon sources such as glucose or lactate are present, in which case it is excreted from the cell or incorporated for lipid synthesis.
N. gonorrhoeae lack the
glyoxylate shunt, preventing them from using acetate to form CAC intermediates to replenish the cycle. The membrane-bound LDHs have been determined to be
flavoprotein-containing respiratory enzymes that directly oxidize lactate to reduce
ubiquinone. While these enzymes do not directly pump protons (H+ ions) into the periplasmic space, it is proposed that the reduction of ubiquinone by these enzymes is capable of feeding into the larger ETC. Several enzymes contribute electrons to the intramembranous ubiquinone pool, the first step in the ETC. These include the membrane-bound LDHs (LldD and LdhD),
NADH:ubiquinone oxidoreductase (aka NADH dehydrogenase; Nuo complex I), Na+-translocating NADH dehydrogenase (Nqr),
succinate dehydrogenase (SDH), and the membrane-bound NAD+-independent malate:quinone-oxidoreductase (MqR). In the case of the former, electrons can then be passed from the
bc1 complex along two alternative pathways via the reduction of either cytochrome
c4 or
c5. Both of these cytochromes transfer electrons to the terminal cytochrome
ccb3 oxidase for the reduction of O2 to form H2O under aerobic conditions. The general purpose of the ETC is the formation of the electrochemical gradient of hydrogen ions (H+ or protons), resulting from concentration differences across the plasma membrane, needed to power ATP production in a process known as
oxidative phosphorylation. In gonococci, movement of protons into the periplasmic space is accomplished by the Nuo complex I, the cytochrome
bc1 complex, and cytochrome
ccb3. Subsequently, ATP synthesis is performed by the
F1F0 ATP synthase, a two-part protein complex present in gonococci as well as numerous other species across phylogenetic domains. This complex couples proton translocation back into the cytoplasm along its gradient with mechanical rotation to generate ATP.
Iron The general purpose of the ETC is the formation of the electrochemical gradient of hydrogen ions (H+ or protons), resulting from concentration differences across the plasma membrane, needed to power ATP production in a process known as
oxidative phosphorylation. Along with the sequestration defence that can be further upregulated by host inflammation, humans also produce
siderocalins that can chelate siderophores as a further method of inhibiting pathogenic bacterial growth. These are sometimes ineffective against
N. gonorrhoeae, which can colonize intracellularly, particularly in phagocytic cells such as
macrophages and neutrophils. Increases in host intracellular iron also downregulate some of the intracellular pathogen-killing mechanisms; coincidentally, pathogenic
Neisseria can alter several host cell mechanisms that ultimately allow the pathogen to take most of the available iron from the host immune cell.
Opa proteins Phase-variable opacity-associated (Opa) adhesin proteins are used by
N. gonorrhoeae as part of evading the immune response in a host cell. At least 12 Opa proteins are known, and the many variations of surface proteins make recognizing
N. gonorrhoeae and mounting a defense by immune cells more difficult. Opa proteins are in the outer membrane and facilitate a response when the bacteria interacts with a variety of host cells. These proteins bind to various epithelial cells, and allow
N. gonorrhoeae to increase the length of infection as well as increase the amount of invasion into other host cells.
Type IV pili Dynamic
polymeric protein filaments called
type IV pili allow
N. gonorrhoeae to do many bacterial processes, including adhesion to surfaces, transformation competence, twitching motility, and immune response evasions. To enter the host the bacteria uses the pili to adhere to and penetrate mucosal surfaces. The pili are a pivotal
virulence factor for
N. gonorrhoeae; without them, the bacterium is unable to promote colonization. For motility, individual bacteria use their pili in a manner that resembles a grappling hook: first, they are extended from the cell surface and attach to a
substrate. Subsequent pilus retraction drags the cell forward. The resulting movement is referred to as twitching motility.
N. gonorrhoeae can pull 100,000 times its own weight, and the pili used to do so are amongst the strongest biological motors known to date, exerting one
nanonewton. This process allows
N. gonorrhoeae to recombine its genes and alter the
antigenic determinants that adorn its surface, Simply stated, the chemical composition of molecules are changed due to changes at the genetic level. In addition to gene rearrangement, it is also
naturally competent, meaning it can acquire extracellular DNA from the environment via its type IV pilus, specifically proteins PilQ and PilT. These processes allow
N. gonorrhoeae to acquire and spread new genes, disguise itself with different surface proteins, and prevent the development of
immunological memory – an ability which has contributed to antibiotic resistance and impeded vaccine development.
Phase variation Phase variation is similar to antigenic variation, but instead of changes at the genetic level altering the composition of molecules, these genetic changes result in the activation or deactivation of a gene. However, a significant fraction of the gonococci can resist killing through the action of their
catalase, The bacterial RecA protein, which mediates repair of DNA damage, plays a crucial role in gonococcal survival.
N. gonorrhoeae may replace DNA damaged in neutrophil phagosomes with DNA from neighboring gonococci. The process in which recipient gonococci integrate DNA from neighboring gonococci into their genome is called transformation. == Genome ==