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Overview: Microbial Pathogenesis

Beginning at birth, microbial organisms enter and leave the body, primarily on external or mucosal surfaces. Some of these predominantly commensal organisms become resident; others are transient; and still others establish latent foci in otherwise sterile spaces. Over a lifetime, a person is the reservoir for hundreds of strains of viruses, thousands of bacterial species, and a scattering of fungi and parasites. When these organisms violate their niche, invade, or produce toxic products, and at the same time overcome innate and adaptive host defenses, virulent interactions take place and occasionally lead to disease. Organisms can cause disease without entering or adhering to tissues by releasing toxic products. However, all infections caused by obligate intracellular parasites such as viruses require attachment of microbes onto cells and subsequent intracellular invasion as typified by the viral hemagglutinin molecule on the surface of the influenza virus, which determines species and tissue tropism, transmissibility, and replication.1,2

Binding to cells does not always occur with bacterial pathogens, particularly in the lung. In contrast to the GI tract where most bacterial pathogens must attach to surfaces and some, such as Shigella dysenteriae, do enter into cells, many studies with common respiratory bacterial pathogens such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pyogenes, and others have found that avoidance of binding to respiratory epithelial cells promotes progression of infection and development of disease. Thus, the statement that one often encounters that bacterial binding to epithelial cells initiates infection in the respiratory tract is not correct for some prominent lung pathogens. This is likely due, in large part, to the role of bacterial cell binding to the respiratory epithelium in promoting clearance of most organisms entering the lung (see Chapter 121). This occurs by a variety of nonspecific innate immune mechanisms that are potently activated by microbial binding to epithelial surface or, following binding and internalization, binding to intracellular toll-like receptors (TLRs) and other conserved pattern-recognition molecules. Along with induction of cytokine synthesis and release there is a rapid activation of beneficial inflammation and clearance. In some situations, however, organisms are able to avoid such clearance and propagate and produce clinical symptoms. For example, in neutropenic mice, the infectious dose of P. aeruginosa applied to the nose of an anesthetized animal that produces a lethal pneumonia and sepsis can be in the range of 10 to 50 bacterial cells, whereas in a neutrophil-sufficient setting usually 107 to 108 bacterial cells are needed to initiate infection. Clearly, avoiding polymorphonuclear leukocyte (PMN)-mediated clearance initiated by innate immunity is essential for serious disease due to P. aeruginosa. This finding highlights how pathologic conditions in the host can predispose to entry and survival of microbes, ranging from breaks in mucosal surfaces to defects in the immune system (see Chapter 121). Organisms become parasites when they express the requisite virulence determinants to gain entry and overcome or evade host ...

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