Fig. 2.

Proposed model for the onset of invasive meningococcal disease.

Following transmission and colonization of the human nasopharynx, the founder clone starts proliferating. During this phase, extensive phenotypic variation is generated by the stochastic reassortment of virulence factors (surface determinants and genes involved in host-pathogen interaction) driven by meningococcal chromosomic variability factors (step 1). This exploration of new phenotypic solutions can lead to the accidental onset of a virulent variant (step 2), which is able to penetrate the nasopharyngeal epithelial barrier and cause septicemia (step 3).