Chapter 120

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.

### Microbial Entry and Adherence

#### Entry Sites

A microbial pathogen can potentially enter any part of a host organism. In general, the type of disease produced by a particular microbe is often a direct consequence of its route of entry into the body. The most common sites of entry are mucosal surfaces (the respiratory, alimentary, and urogenital tracts) and the skin. Ingestion, inhalation, and sexual contact are typical routes of microbial entry. Other portals of entry include sites of skin injury (cuts, bites, burns, trauma) along with injection via natural (i.e., vector-borne) or artificial (i.e., needle-stick injury) routes. A few pathogens, such as Schistosoma species, can penetrate unbroken skin. The conjunctiva can serve as an entry point for pathogens of the eye, which occasionally spread systemically from that site.

Microbial entry usually relies on the presence of specific factors needed for persistence and growth in a tissue. Fecal-oral spread via the alimentary tract requires a biologic profile consistent with survival in the varied environments of the gastrointestinal tract (including the low pH of the stomach and the high bile content of the intestine) as well as in contaminated food or water outside the host. Organisms that gain entry via the respiratory tract survive well in small moist droplets produced during sneezing and coughing. Pathogens that enter by venereal routes often survive best in the warm moist environment of the urogenital mucosa and have restricted host ranges (e.g., Neisseria gonorrhoeae, Treponemapallidum, and HIV).

The biology of microbes entering through the skin is highly varied. Some of these organisms can survive in a broad range of environments, such as the salivary glands or alimentary tracts of arthropod vectors, the mouths of larger animals, soil, and water. A complex biology allows protozoan parasites such as Plasmodium, Leishmania, and Trypanosoma spp. to undergo morphogenic changes that permit transmission of the organism to mammalian hosts during insect feeding for blood meals. Plasmodia are injected as infective sporozoites from ...

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