Mechanisms Of Pathogenesis

From a microbe's perspective, the interior of the human body is a lucrative source of nutrients, provided that some of the obstacles of the innate and adaptive immune systems can be overcome. The ability to subvert these defenses and cause damage is what separates the pathogenic microbes from the multitudes of other microorganisms that inhabit this planet. The methods that disease-causing microbes use to either evade the host defenses or cause damage are called mechanisms of patho-genicity. The arsenal of mechanisms that an individual pathogen possesses is collectively referred to as its virulence determinants. The DNA encoding these virulence factors can sometimes be transferred to other bacteria. ■ genetic transfer of virulence factors, p. 212

The innate and adaptive immune systems do not need to be overcome indefinitely, simply long enough for the pathogen to multiply and then successfully exit the host. A pathogen that is too adept at overcoming the host defenses and causing damage is actually at a disadvantage because its opportunity to be transmitted may be limited and it loses an exclusive source of nutrients if the host dies. In fact, pathogens and their hosts generally evolve over time to a state of balanced pathogenic-ity; the pathogen becomes less virulent while simultaneously the host becomes less susceptible. This was demonstrated when the myxoma virus was intentionally introduced into Australia in the early 1950s to kill the burgeoning rabbit population. Shortly after introduction of the virus, the rabbit population plummeted. Eventually, however, the numbers of rabbits again began increasing. Viruses recovered from surviving rabbits were shown to be less virulent than the original strain, while at the same time the rabbits themselves were more resistant to the original virus strains.

The mechanism by which a microorganism causes disease generally follows one of several patterns:

■ Production of toxins that are then ingested.

The microorganism does not grow on or in the host, so this is not an infection but rather a foodborne intoxication, a form of food poisoning. The only virulence determinant that these bacteria require is toxin production. Relatively few organisms cause foodborne intoxication, but these include Clostridium botulinum, which causes botulism, toxin-producing strains of Staphylococcus aureus, which cause staphylococcal food poisoning, and the fungus Claviceps purpurea, which causes ergot poisoning.

■ botulism, p. 672 ■ Staphylococcus aureus foodborne intoxication, p. 812

■ Colonization of surface of the host, followed by toxin production. The microorganism multiplies to high numbers on a host surface, such as the respiratory or intestinal tract. There, the microbes produce a toxin that interferes with cell function, sometimes structurally damaging the cell. Examples of bacteria that use this strategy include Vibrio cholerae, which causes cholera, E. coli O157:H7, which causes bloody diarrhea, and Corynebacterium diphtheriae, which causes diphtheria. ■ cholera, p. 611 ■ E. coliO157:H7 diarrhea, p. 615 ■ diphtheria, p. 568

■ Invasion of host tissues. The microbe penetrates the first-line defenses, breaching the body's barriers, and then multiplies within the tissues. Organisms that use this strategy generally have mechanisms to avoid destruction by macrophages; additionally, some have mechanisms to avoid detection by antibodies. There are numerous examples of bacteria that use this strategy, including Mycobacterium tuberculosis, Yersinia pestis, Salmonella species, and Streptococcus pyogenes.

■ Mycobacterium tuberculosis, p. 582 ■ Yersinia pestis, p. 724

■ Salmonella, p. 616 ■ Streptococcus pyogenes, p. 565

■ Invasion of host tissues, followed by toxin production. These organisms are similar to those in the previous category, but in addition to their other attributes, they also make toxins. Examples include Shigella dysenteriae and certain strains of Streptococcus pyogenes. ■ Shigella, p. 613

Awareness of the pathogenic strategies of microorganisms and viruses is important because they illustrate why only certain microbes are able to cause disease in a healthy host. They also help explain the epidemiology and symptoms associated with the various diseases described later in the textbook.

In the next sections we will describe the mechanisms that pathogens use to adhere to and colonize host tissue, avoid innate defenses, avoid adaptive defenses, and, finally, cause the damage associated with disease. We will focus on mechanisms used by bacterial pathogens because these are by far the most thoroughly characterized; later in the chapter we will discuss mechanisms of pathogenicity of viruses and eukaryotic organisms. As we describe various virulence determinants, recognize that their attributes are not mutually exclusive; a single structure on a cell can serve more than one purpose.

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  • lamorac
    What is causative agent mechanism?
    3 years ago

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