By Levi Clancy for Student Reader on
Koch's Postulates determine if a microbe causes a disease. Koch's Molecular Postulates determine specific genes are associated with virulence.
However, there are many examples where it has proven impossible to satisfy all of Koch's postulates for a putative pathogen.
Koch's Original Postulates
The bacterium must be present in every case of the disease.
The bacterium must be isolated from the diseased host & grown inpureculture.
The specific disease must be reproduced when a pure culture of the bacterium is inoculated into a healthy susceptible host.
The bacterium must be recoverable from the experimentally infected host.
Koch's Molecular Postulates
The phenotype under investigation should be associated significantly more often with the pathogenic organism than with nonpathogenic members or strains.
Specific inactivation of a gene (or genes) associated with the suspected virulence trait should lead to a measurable decrease in virulence.
Restoration of full pathogenicity should accompany replacement of the mutated gene with the wild type original.
Exceptions to Koch's Postulates
Some microbes are obligate intracellular parasites (like chlamydia or viruses) and are very challenging, or even impossible, to grow on artificial media.
Some diseases, such as tetanus, have variable signs and symptoms between patients.
Some diseases, such as pneumonia & nephritis, may be caused by a variety of microbes.
Some pathogens, such as S. pyogenes, cause several different diseases.
Certain pathogens, such as HIV, cause disease in humans only -- it is unethical to purposefully infect a human.
For example, Helicobacter pylori and Salmonella typhi did not satisfy (III) because initially there was no animal models, thus disease could not be reproduced. [To get around this, researchers used "model" pathogens in conjunction with "model" hosts. H. mustelae was used with ferrets as host, and S. typhimurium was used with mice as host. Human volunteer studies and the recent development of an animal model for H. pylori-induced ulcers have now satisfied Koch's 3rd postulate.
Chlamydia pneumoniae fails (I) because it is sometimes not found in diseased (atherosclerosis) individuals. However, the ability to culture Chlamydia pneumoniae from atherosclerotic plaques taken from experimentally infected animals was used to support the role of this bacterium in disease.
Also, Chlamydia sp. or Treponema pallidum are examples of bacteria difficult to grow (II). However, methods for culturing these organisms DO exist. C. botulinum toxin acts at a distance, so bacteria only recovered in stool (if at all), not in nervous system (postulate I). But the fact that toxin reproduces disease is important here, as toxin.
Strep. mutans: Miller originally failed to isolate this pathogen because of anaerobic and multi-species community requirements, thus (II) was initially not satisfied. However, Clark (1924) and Keyes & Fitzgerald (1960's) did succeed in culturing mutans streptococci and could transfer disease through contaminated feces or plaques.