Schmid-Hempel, P. and Frank, S. A. 2007. Pathogenesis, virulence, and infective dose. PLoS Pathogens 3(10):e147.

Some pathogens can begin an infection with only a small number of cells in the initial inoculum. For example, enterohemorrhagic strains of Escherichia coli require an infective dose of only about ten cells. By contrast, other pathogens, such as Vibrio cholerae, require a large number of cells (103 to 108 cells) in the inoculum to successfully infect a host (Figure 1).

We propose a new hypothesis to explain the wide diversity of infective dose among pathogens. In our hypothesis, the biochemical mechanisms of pathogenesis, which typically facilitate invasion by evading host immune defenses, explain much of the variation in infective dose. If these pathogenic mechanisms act locally, then we predict that the infective dose will be low; if the pathogenic molecules tend to diffuse and act at a distance, then we predict that the infective dose will be high. Local action requires relatively few molecules and therefore relatively few infecting cells. Distant action requires that the infecting population of pathogens builds up sufficient quantities of diffusible molecules to achieve sufficient effect before the host can clear the infection (the “frontal attack strategy” described in [1]); thus, larger infecting doses are required to produce sufficient concentrations of the diffusible pathogenic molecules. Few standardized studies of infective dose have been conducted, in part because there has never been a clear conceptual framework within which to study the problem and formulate testable predictions. To test our hypothesis, we therefore use the reasonably standardized databases of the United States Food and Drug Administration [2] and Health Canada [3], supplemented by additional references.


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