++
Over the past four decades, molecular studies of the pathogenesis of microorganisms have yielded an explosion of information about the various microbial and host molecules that contribute to the processes of infection and disease. These processes can be classified into several stages: microbial encounter with and entry into the host; microbial growth after entry; avoidance of innate host defenses; tissue invasion and tropism; tissue damage; and transmission to new hosts. Virulence is the measure of an organism’s capacity to cause disease and is a function of the pathogenic factors elaborated by microbes. These factors promote colonization (the simple presence of potentially pathogenic microbes in or on a host), infection (attachment and growth of pathogens and avoidance of host defenses), and disease (often, but not always, the result of activities of secreted toxins or toxic metabolites). In addition, the host’s inflammatory response to infection greatly contributes to disease and its attendant clinical signs and symptoms. The recent surge of interest in the role of the microbiota and its associated microbiome—the collection of microbial genomes residing in or on mammalian organisms—in the physiology of, susceptibility to, and response to infection and in immune system development has had an enormous impact on our understanding of host-pathogen interaction.
++
(See also Chap. 3) We now understand that the indigenous microbial organisms living in close association with almost all animals are organized into complex communities that strongly modulate the ability of pathogenic microbes to become established in or on host surfaces. The sheer numbers of these microbes and their genomic variability vastly exceed the numbers of host cells and genes in a typical animal. Changes and differences in microbiomes within and between individuals, currently characterized by high-throughput DNA sequencing techniques and bioinformatic analysis, affect the development and control of the immune system as well as such diverse conditions as obesity, type 1 diabetes, cognition, neurologic states, autoimmune diseases, and infectious diseases of the skin, gastrointestinal tract, respiratory tract, and vagina. It has been more difficult to directly associate specific types of microbiomes with pathophysiologic states and to assess how conserved or variable microbial species within human and animal microbiomes are evolving. Defining clusters of organisms associated with diseases may become more feasible as more data are obtained. Complicating this task are the results from the Human Microbiome Project suggesting a high level of variability among individuals in the components of the microbiome, although many individuals appear to maintain a fairly conserved microbiome throughout their lives. In the context of infectious diseases, clear changes and disruptions of the indigenous microbiome have a strong and often fundamental impact on the progression of infection. Such alterations can be associated with the effects of antibiotic and immunosuppressive drug use on the normal flora, with environmental changes, and with the impact of microbial virulence factors that displace the indigenous microbial flora to facilitate pathogen colonization. As the available technology for defining the ...