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1.6.5: Koch's Postulate

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    Learning Objectives
    • Summarize Koch’s postulates and molecular Koch’s postulates, respectively, and explain their significance and limitations
    • Explain the concept of pathogenicity (virulence) in terms of infectious and lethal dose
    • Distinguish between primary and opportunistic pathogens and identify specific examples of each
    • Summarize the stages of pathogenesis
    • Explain the roles of portals of entry and exit in the transmission of disease and identify specific examples of these portals

    For most infectious diseases, the ability to accurately identify the causative pathogen is a critical step in finding or prescribing effective treatments. Today’s physicians, patients, and researchers owe a sizable debt to the physician Robert Koch (1843–1910), who devised a systematic approach for confirming causative relationships between diseases and specific pathogens.

    Koch’s Postulates

    In 1884, Koch published four postulates that summarized his method for determining whether a particular microorganism was the cause of a particular disease. Each of Koch’s postulates represents a criterion that must be met before a disease can be positively linked with a pathogen. In order to determine whether the criteria are met, tests are performed on laboratory animals and cultures from healthy and diseased animals are compared (Figure \(\PageIndex{1}\)).

    Koch’s Postulates
    1. The suspected pathogen must be found in every case of disease and not be found in healthy individuals.
    2. The suspected pathogen can be isolated and grown in pure culture.
    3. A healthy test subject infected with the suspected pathogen must develop the same signs and symptoms of disease as seen in postulate
    4. The pathogen must be re-isolated from the new host and must be identical to the pathogen from postulate 2.
    A diagram Koch’s postulates. 1 – The suspected causative agent must be absent from all healthy organisms but present in all diseased organisms. This is demonstrated by looking at slides under a microscope from a sick mouse and seeing the suspected agent. A slide from a healthy mouse only shows healthy red blood cells. 2 – The causative agent must be isolated from the diseased organism and grown in pure culture. This is demonstrated by showing grown on a petri plate from the sick mouse and no growth from the healthy mouse. 3 – The cultured agend must cause the same disease when inoculated into a healthy, susceptible organism. This is demonstrated by injecting a healthy mouse with the cultured agent and having that mouse get sick. 4 – The same causative agent must then be reisolated from the inoculated diseased organism. This is demonstrated by a petri plate from this last mouse showing growth of the causative agent.
    Figure \(\PageIndex{1}\): The steps for confirming that a pathogen is the cause of a particular disease using Koch’s postulates.

    In many ways, Koch’s postulates are still central to our current understanding of the causes of disease. However, advances in microbiology have revealed some important limitations in Koch’s criteria. Koch made several assumptions that we now know are untrue in many cases. The first relates to postulate 1, which assumes that pathogens are only found in diseased, not healthy, individuals. This is not true for many pathogens. For example, H. pylori, described earlier in this chapter as a pathogen causing chronic gastritis, is also part of the normal microbiota of the stomach in many healthy humans who never develop gastritis. It is estimated that upwards of 50% of the human population acquires H. pylori early in life, with most maintaining it as part of the normal microbiota for the rest of their life without ever developing disease.

    Koch’s second faulty assumption was that all healthy test subjects are equally susceptible to disease. We now know that individuals are not equally susceptible to disease. Individuals are unique in terms of their microbiota and the state of their immune system at any given time. The makeup of the resident microbiota can influence an individual’s susceptibility to an infection. Members of the normal microbiota play an important role in immunity by inhibiting the growth of transient pathogens. In some cases, the microbiota may prevent a pathogen from establishing an infection; in others, it may not prevent an infection altogether but may influence the severity or type of signs and symptoms. As a result, two individuals with the same disease may not always present with the same signs and symptoms. In addition, some individuals have stronger immune systems than others. Individuals with immune systems weakened by age or an unrelated illness are much more susceptible to certain infections than individuals with strong immune systems.

    Koch also assumed that all pathogens are microorganisms that can be grown in pure culture (postulate 2) and that animals could serve as reliable models for human disease. However, we now know that not all pathogens can be grown in pure culture, and many human diseases cannot be reliably replicated in animal hosts. Viruses and certain bacteria, including Rickettsia and Chlamydia, are obligate intracellular pathogens that can grow only when inside a host cell. If a microbe cannot be cultured, a researcher cannot move past postulate 2. Likewise, without a suitable nonhuman host, a researcher cannot evaluate postulate 2 without deliberately infecting humans, which presents obvious ethical concerns. AIDS is an example of such a disease because the human immunodeficiency virus (HIV) only causes disease in humans.

    Exercise \(\PageIndex{1}\)

    Briefly summarize the limitations of Koch’s postulates.

    Key Concepts and Summary

    • Koch’s postulates are used to determine whether a particular microorganism is a pathogen.

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