A survey has been made of Neisseria meningitidis strains isolated from patients in order to determine the prevalence of diffusible growth inhibitory substances active against other meningococci. Three types of growth inhibitory activity could be distinguished. The first type was released in cultures of nearly all strains after treatment with chloroform vapour. This activity inhibited all meningococci tested, including the donor strain. The properties were similar to those of the non‐specific growth inhibitors observed among most strains of N. gonorrhoeae. The second type was demonstrated in cultures from four strains among 215 strains tested and may be present in a fifth strain. Bactericidal activity with high strain specificity was spontaneously released from cultures of the four strains. This type of activity was found to fit the description of a bacteriocin. The third type of inhibition was observed in one strain among the 215 strains tested. Cultures of this strain spontaneously released bacteriostatic activity. Products from the strain could inhibit almost all meningococcal strains except the donor strain itself. This activity was not entirely blocked by bovine serum albumin; it was not abolished by pronase and it was not stopped by dialysis membranes with cut‐off 12000.

The bactericidal activity found in four strains of Neisseria meningitidis and the bacteriostatic effect observed in one were expressed in the exponential phase of batch cultures and continued during the stationary phase. The active material was stable for more than 50 hours in agar media. In mixed cultures a strain with inhibitory activity eradicated a sensitive strain, and dominated the culture in the latter part of the exponential phase. Recombination took place in mixed cultures when at least one of the strains had the genetic properties which determine competence in transformation. The presence of inhibitory activity increased the recombination frequency at least ten‐fold. Genetic markers were introduced into a strain with inhibitory activity from sensitive strains of N. meningitidis and from N. cinerea.

In the Neisseria meningitidis strain MC58 (serogroup B; ET-5 complex) genome three putative islands of horizontally transferred DNA (IHTs) have been identified. IHT-A2 codes for eight hypothetical proteins and two disrupted open reading frames with similarity to a secretion protein (NMB0097) and an ABC transporter (NMB0098). The strains MC58 and 44/76 (shown here) are meningocin resistant/weakly sensitive. None of these strains are meningocin producers. However, NMB0097 and NMB0098 homologues with open reading frames are found in meningocin producers (N. meningitidis P241 (serogroup A; systemic isolate) and BT878 (serogroup B; carrier isolate), and also in strain FAM18 (serogroup C; ET-37 complex). Knocking out either of the two genes in the strain BT878 yielded mutants that did not secrete meningocin. A similarly disrupted tolC mutant in strain BT878 still released meningocin. Among systemic meningococcal isolates prior to and at the onset (mid-1973 to the end of 1974) of the epidemic peaking in 1975 in North Norway, 12 of 30 (40%) isolates of serogroup A were meningocin producers. However, the rate for serogroup B was 1 of 45 (2.2%). Serogroup B meningocin-resistant/weakly sensitive non-producers dominated in the region from mid-1975 and spread to the rest of the country from then on. No producers were found in selected pharyngeal isolates from healthy carriers collected in Svalbard in the early spring of 1975. Our results suggest that meningocinogeny has played a part in the change from serogroup A to serogroup B among isolates in North Norway during the first half of 1975.

Influence of blood cells on the expression of bacteriocin-like activity in Neisseriu meningifidis. Acta path. microbiol. immunol. scand. Sect. B, 91: 245-250, 1983.The inhibitors responsible for the bactericidal activity found in four strains of Neisseriu meningitidis were strongly bound to or inactivated by blood cells. The bactericidal effects were specifically influenced by human cells of types 0, A. B and AB. Cells from horse, sheep and rabbit had no significant effect. The bacteriostatic effect observed in one strain of N . meningitidis was more moderately reduced in the presence of animal cells as well as human cells. The effects of the blood cells were connected with pellets from lysates of the blood cells. The bacteriostatic effect was also moderately reduced in the presence of plasma, hemoglobin and methemoglobin regardless of origin, and to some extent of cytochrome C. CaCl2 slightly enhanced the bacteriostatic effect.

Strains of Neisseria meningitidis isolated from patients were more often completely insensitive to five bacteriocin‐like agents than carrier strains, but no particular bacteriocin type could be associated with patient strains. Two genetically distinct types of insensitivity could be separated by transformation. Insensitivity to four bactericidal agents (from the strains P201, P213, P241 and 99/79) was caused by one common genetic marker whereas insensitivity to a bacteriostatic agent (from the strain 77/79) was caused by another. Insensitivity to the bactericidal agents was more often found among strains belonging to serogroup B than among strains belonging to other groups. But group B strains from patients were more often insensitive than similar strains from carriers. Insensitivity to the bacteriostatic agent seemed evenly distributed among strains of various serogroups. All insensitive patient strains tested showed reduced binding/destruction of inhibitor, indicating that resistance and not tolerance is associated with patient strains.