Host-Pathogen Interactions: Redefining the Basic Concepts of Virulence and Pathogenicity

While preparing to teach the Microbial Pathogenesis graduate course at our institution, we found ourselves struggling to find basic definitions of virulence and pathogenicity that incorporated the contributions of both the host and the pathogen. The generally used definition of a pathogen as a microbe that causes disease in a host (Table 1) seemed inadequate, because some microbes do not cause clinically evident disease in all hosts. As we investigated the origins of the modern concepts of microbial pathogenesis, we found that while the importance of a host’s susceptibility for a microbe’s virulence was often recognized, the existing definitions did not account for the contributions of both pathogen and host. Historical definitions of pathogens were based on their ability to cause disease as an invariant trait. An integrated view of microbial pathogenesis accounting for the contributions of both host and pathogen has not been developed. In this article, we review historical concepts of microbial pathogenicity and virulence, propose new definitions, and suggest a classification system for microbial pathogens based on their ability to cause damage as a function of the host’s immune response.