Microbiology, 2021

15.2 • How Pathogens Cause Disease 619
Figure 15.4
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