16. Microbial Mechanisms of Pathogenicity
16.2 How Pathogens Cause Disease
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 sizeable 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 (Table 16.3) 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 16.4).
Table 16.3. Koch’s Postulates
| 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 1. |
| (4) The pathogen must be re-isolated from the new host and must be identical to the pathogen from postulate 2. |
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