Lactate enhancement of sialylation of gonococcal lipopolysaccharide and of induction of serum resistance by CMP-NANA is not due to direct activation of the sialyltransferase: metabolic events are involved

Microb Pathog. 1996 Sep;21(3):193-204. doi: 10.1006/mpat.1996.0054.

Abstract

Lactate enhances lipopolysaccharide (LPS) sialylation and induction of serum resistance in gonococci by CMP-NANA. To investigate whether the enhancement is due to a direct effect on the sialyltransferase, an improved extraction of the enzyme and a reliable quantitative assay were devised. Gonococci (strain F62) were disrupted in a French pressure cell and the bacterial membranes were extracted for 1 h at 37 degrees C with a detergent, NONIDET (1% v/v). The assay involved sialylation of LPS by CMP-14CNANA and scintillation counting of the labelled LPS after fixing it on filter paper strips by trichloracetic acid (TCA) and washing away unincorporated CMP-14CNANA. It was rapid, reproducible and, although the enzyme preparations contained endogenous LPS, was dependent upon added LPS for maximum activity. At 37 degrees C the rate was constant for up to 5 min and proportional to the concentration of extract in the assay. A wide range of concentrations of lithium-L-lactate did not enhance the activity of the extracted sialyltransferase. At concentrations above 22 microM, it was inhibitory. Pre-incubation of gonococci with lactate enhanced subsequent LPS sialylation and induction of serum resistance by CMP-NANA. Hence, the process whereby lactate enhances the effect of CMP-NANA is separate from the action of CMP-NANA itself. Both processes were inhibited by a sublethal concentration of chloramphenicol, indicating that metabolic events are required. Evidently, the enhancement process does not involve a direct activation of the sialytransferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Bactericidal Activity*
  • Cytidine Monophosphate N-Acetylneuraminic Acid / pharmacology*
  • Enzyme Activation
  • Lactic Acid / pharmacology*
  • Lipopolysaccharides / metabolism*
  • Models, Biological
  • Neisseria gonorrhoeae / drug effects
  • Neisseria gonorrhoeae / enzymology
  • Neisseria gonorrhoeae / metabolism*
  • Sialyltransferases / metabolism*

Substances

  • Lipopolysaccharides
  • Cytidine Monophosphate N-Acetylneuraminic Acid
  • Lactic Acid
  • Sialyltransferases