Joined: May 2002
There is a certain sad irony here, and I'm not talking about meningitis being a disease of the brain...
SFI Working Paper Abstract
Title: Two-Tiered Evolution of “Neiserria meningitis”: How Within-Host Ecology and Between-Host Epidemiology Expedite Phase Shifting
Author(s): Lauren W. Ancel, Bruce R. Levin, Anthony R. Richardson, and Igor Stojiljkovic
Abstract: Many so-called pathogenic bacteria make their living as commensals or even symbionts of the hosts that they colonize. Bacteria such as “Neiserria Meningitidis,” “Haemophilus influenzae,” “Staphylococcus aureus (1),” “Streptococcus pneumoneae,” “Helicobacter pylori,” and “Echerichia coli” are far more likely to colonize and maintain their populations in healthy individuals, asymptomatically, than to cause disease. Moreover, the members of these otherwise benign or beneficial species that are actually responsible for diseases like meningitis and sepsis, are not transmitted to new hosts and are therefore at an ecological and evolutionary dead-end. This implies that the virulence factors responsible for the pathogenicity of these bacteria must evolve in response to selection pressures other than those for causing disease. What are these pressures? Here we consider “Neisseria meningitidis”--a common member of the commensal flora of the nasal pharyngeal passages of humans that is also responsible for sporadic and epidemic meningitis. We focus on the evolution of phase shifting--a mutational process that turns genes on and off and, in particular, genes that code for virulence determinants such as pili, lipopolysaccharide, capsular polysaccharide, and outer membrane proteins.
Using mathematical models, we offer two testable hypotheses: First, within a single human host, fast phase shifting leads to virulence. And second, although virulence may be disadvantageous within the framework of a single host, fast phase shifting may evolve in response to selection operating at a multihost epidemiological level. We discuss avenues for empirically testing these hypotheses and the implications of this work for the evolution of virulence in general.
Keywords: evolution, epidemiology, mutation rate, phase shifting, virulence, Neisseria meningitis