Mp. Bos et al., SELECTION OF OPA(-GONORRHOEAE BY LIMITED AVAILABILITY OF NORMAL HUMANSERUM() NEISSERIA), Infection and immunity, 65(2), 1997, pp. 645-650
Experimental infections of human male volunteers with Neisseria gonorr
hoeae have provided valuable insights into the early stages of gonorrh
eal disease. Bacterial variants expressing outer membrane opacity (Opa
) proteins appear to be selected from the inoculum during a period in
which total recoverable numbers of bacteria decrease rapidly. This app
arent survival advantage occurs simultaneously with the onset of an in
flammatory response, characterized by local production of interleukin
6 (IL-6) and IL-8 and the appearance of leukocytes in urine. Since the
inflammatory response may also result in the presence of serum factor
s on the mucosal surface, we investigated the possibility that killing
in normal human serum (NHS) leads to the selection of Opa(+) variants
. We therefore studied killing of separate populations and mixtures of
Opa(-) and Opa(+) N. gonorrhoeae MS11mk in NHS. Expression of an Opa
protein conferred a survival advantage upon the organism; i.e., the Op
a(+) variants were more serum resistant than their isogenic Opa(-) cou
nterparts, resulting in a selection for Opa(+) phenotypes when a mixtu
re of Opa(+) and Opa(-) gonococci (GC) was exposed to submaximal doses
of NHS. This selection was observed in three different lipooligosacch
aride (LOS) backgrounds, indicating that it was not due to a differenc
e in LOS expression between Opa(-) and Opa(+) phenotypes. Incubation i
n NHS of sialylated GC resulted in a similar selection for Opa(+) vari
ants. The presence of normal human urine during the serum killing assa
y had no effect on the selection phenomenon but drastically depleted N
HS of bactericidal activity, which was found to be at least partly due
to complement inhibition. The results suggest that serum killing may
contribute to the transition from Opa(-) to Opa(+) phenotypes during t
he early stages of infection of the male urethra.