Lactate causes changes in gonococci including increased lipopolysaccharide synthesis during short-term incubation in media containing glucose

Abstract

Gonococci (strain BS4(agar)), emerging from lag-phase during 1-1.5 h incubation in a medium containing glucose (28 mM) and either 5 microM or 50 microM sodium lactate, show enhanced capacity for their lipopolysaccharide (LPS) to be sialylated by cytidine 5'-monophospho-N-acetyl neuraminic acid. The sialyltransferase content of the lactate-treated gonococci was not greater than that of control organisms and showed no differences in LPS components. However, the total LPS content of the lactate-treated gonococci was 10-20% higher than that of control organisms, so lactate enhancement may be due to more sialyl receptors becoming available due to an overall stimulation of LPS synthesis. The protein and pentose contents of the lactate-treated gonococci were also higher than those of controls, indicating stimulation of protein synthesis and ribosome production. Electron microscopy showed hair-like external appendages on control but not on lactate-treated gonococci. The above growth conditions are unnatural. However, when concentrations of glucose and lactate were adjusted to values akin to those occurring in vivo (glucose 5 mM alone and with either 1 mM or 10 mM lactate), and gonococcal multiplication occurred during the short incubation period (1-1.5 h), lactate again induced greater contents of LPS, protein and pentose. A high content of LPS, which will contribute to pathogenicity, should be a constant feature of gonococci growing in human urogenital tissues, where lactate is ever present with glucose.

Growth of Neisseria gonorrhoeae in the Female Mouse Genital Tract Does Not Require the Gonococcal Transferrin or Hemoglobin Receptors and May Be Enhanced by Commensal Lactobacilli

“…In vivo, the reduced pH resulting from acid production by lactobacilli may cause the release of iron from murine transferrin and lactoferrin. An additional way by which lactobacilli might enhance gonococcal infection is via the production of lactate, which when used as a carbohydrate source in vitro increases the resistance of gonococci to complement-mediated lysis via induction of higher levels of lipooligosaccharide (20,45) and, in particular, of a lipooligosaccharide species that can be posttranslationally sialylated (41). It should be noted that we generally do not isolate L. murinus from estradiol-treated mice until 4 to 5 days after implantation of the estradiol pellet; this emergence of lactobacilli often parallels the increased recovery of N. gonorrhoeae that occurs during the course of experimental murine infection.…”

Lactate Stimulation of Gonococcal Metabolism in Media Containing Glucose: Mechanism, Impact on Pathogenicity, and Wider Implications for Other Pathogens

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Over the past decade, studies of Neisseria gonorrhoeae have shown that in media containing glucose, lactate stimulates metabolism, and this could affect pathogenicity (7,19). Recently, the probable mechanism of this stimulation has been identified as one that could apply to other pathogens (68).

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Effect of Host Lactate on Gonococci and Meningococci: New Concepts on the Role of Metabolites in Pathogenicity

“…Increased LPS sialylation occurs through greater production of both LPS and the sialyltransferase. There was more rapid emergence from lag phase with lactate and a 20% increase in the rate of logarithmic growth compared with glucose alone (22). Lactate was used more rapidly than glucose in a synthetic medium (22), as was seen in the fluid obtained from subcutaneous plastic chambers in guinea pigs that had been infected with gonococci (25).…”

“…This difference between the species affects the mechanism of increase in sialylated LPS and serum resistance induced by lactate. For gonococci, general stimulation of metabolism by lactate, producing more LPS and sialyltransferase, is predominant (22). For meningococci, the major role of lactate appears to be in promoting sialic acid production for LPS sialylation and incorporation in capsular polysaccharide.…”

“…The enhancing effect of physiological concentrations of lactate on LPS sialylation occurred as gonococci were emerging from lag phase in a medium containing glucose. This resulted from an overall stimulation of metabolism, evidenced by greater LPS production (by 10 to 20%), enhanced protein synthesis (10 to 20%), and larger pentose contents (30 to 60%) (21,22). Increased LPS sialylation occurs through greater production of both LPS and the sialyltransferase.…”