ANAEROBIC GROWTH AND CYTIDINE 5'-MONOPHOSPHO-N-ACETYLNEURAMINIC ACID ACT SYNERGISTICALLY TO INDUCE HIGH-LEVEL SERUM RESISTANCE IN NEISSERIA-GONORRHOEAE

In vivo, gonococci encounter a myriad of conditions not present in vit ro. At some stages of infection and disease, gonococci may grow anaero bically, probably by using sodium nitrite as a terminal electron accep tor. Also, gonococci sialylate their lipooligosaccharide (LOS) in vivo , by using low concentrations of cytidine 5'-monophospho-N-acetylneura minic acid (CMP-NANA) present in host tissue. This sialylation is resp onsible for the acquired resistance of gonococci to both normal and im mune human serum. Given that gonococci grown in the absence of oxygen or in the presence of CMP-NANA probably more closely resemble gonococc i grown inside a human host, we studied the serum resistance of gonoco cci cultivated under these conditions. In the absence of CMP-NANA, ana erobically grown (anaerobic) gonococci were somewhat less sensitive to serum killing than were aerobically grown (aerobic) gonococci. Howeve r, anaerobic gonococci grown with 6 mug of CMP-NANA per ml exhibited a lmost complete serum resistance, while aerobic gonococci required 16-f old-higher CMP-NANA concentrations to achieve significant serum resist ance. Anaerobic gonococci incubated in CMP-NANA converted to serum res istance two to three times faster than did similarly treated aerobic g onococci and incorporated up to six times as much sialic acid into the ir LOS. Gonococci can express several different LOS molecules. Anaerob ic gonococci expressed the LOS molecule that acts as an acceptor for s ialic acid from CMP-NANA in greater quantity than aerobic gonococci di d. Finally, Triton X-100 extracts of anaerobic gonococci contained abo ut four times more sialyltransferase activity than did extracts of aer obic gonococci. Sialyltransferase activity in these extracts was not i nhibited by oxygen or enhanced by anaerobiosis. These data indicate th at anaerobic conditions lead to altered LOS biosynthesis and to induct ion of sialyltransferase activity in gonococci. In vivo, where decreas ed oxygen levels and relevant concentrations of CMP-NANA are found, go nococci could readily become resistant to killing by normal and immune human serum.