To Örebro University

BACKGROUND: Neisseria meningitidis is a human pathogen, carried asymptomatically in the nasopharynx, that can also cause invasive meningococcal disease. Understanding the carriage/invasiveness balance is crucial, and bacterial genetic factors may impact this balance. A previous genome-wide association study reported that the gene porB class 3 was significantly associated with carriage isolates. This study aimed to examine the impact of porB variants on virulence in carriage and invasive meningococcal isolates.

RESULTS: For this, 24 isolates were used (13 invasive and 11 carriage) belonging to different genogroups (B, C, W, Y, and cnl) and selected based on the presence of the genetic variant porB class 2 or class 3. Transgenic BALB/c mice expressing human transferrin were infected intraperitoneally with these isolates. After 3 and 24 h of infection, clinical scores (fur quality, strength, and temperature) and bacterial load in blood were used to evaluate bacterial virulence. The concentrations of inflammatory cytokines were determined from blood. PorB- mutants were created from a carriage and an invasive isolate, and were tested in transgenic mice. The invasive isolates provoked significantly more severe infections compared to the carriage isolates, and the carriage isolates of porB class 3 were significantly less virulent than the invasive isolates of porB class 2 or 3. The invasive PorB- isolate caused milder infections than the parental isolate.

CONCLUSIONS: This study confirms the ability of invasive isolates of N. meningitidis to cause more severe infections than carriage isolates in transgenic mice. The porB expressed in invasive isolates seems to contribute to their higher virulence compared to carriage isolates, although this effect may depend on the genomic context. Notably, differences in virulence were mainly observed among serogroup C and W isolates.