REGULATION OF GONOCOCCAL SIALYLTRANSFERASE, LIPOOLIGOSACCHARIDE, AND SERUM RESISTANCE BY GLUCOSE, PYRUVATE, AND LACTATE

Strain F62 of Neisseria gonorrhoeae gonococci (GC) is sensitive to nor mal human serum unless CMP-N-acetylneuraminic acid (CMP-NANA) is prese nt. NANA is transferred primarily to a 4.5-kDa lipooligosaccharide (LO S) structure by a GC sialyltransferase (Stase), We investigated LOS an d Stase expression and serum resistance in strain F62 grown in differe nt carbon sources and growth conditions, Pyruvate-grown GC expressed 1 .9 to 5.6-fold more Stase activity than did glucose-grown GC, whereas lactate-grown GC generally expressed intermediate Stase activities, Br oth-grown GC expressed two- to fourfold more Stase activity than did p late-grown GC in all carbon sources. Pyruvate- or lactate-grown GC exp ressed significantly more of the sialylateable 4.5-kDa LOS species tha n did glucose-grown GC, Anaerobically, the 4.5-kDa LOS species was exp ressed in greater quantity than the 4.9-kDa N-acetyl galactosamine-ter minating species in all carbon sources, Pyruvate-grown GC also incorpo rated up to threefold more radiolabelled CMP-NANA onto the 4.5-kDa LOS species than did glucose-grown GC, In serum resistance studies, pyruv ate-grown GC were 6.5- to 16.1-fold more serum resistant than glucose- grown GC at limiting CMP-NANA concentrations (1.56 to 12.50 mu g/ml), Taken together, these results indicate that gonococcal expression of S tase activity is up-regulated by growth in pyruvate or lactate, which correlates with enhanced expression of the sialylateable 4.5-kDa LOS a nd, for growth in pyruvate, correlates with enhanced sialylation of go nococcal LOS and greater serum resistance, In different in vivo niches , gonococcal LOS sialylation, serum resistance, and interaction with h ost cells can be highly regulated.