Although the criteria that Koch developed for proving a causal relationship between a microorganism and a specific disease have been of great importance in medical microbiology, it is not always possible to apply them in studying human diseases. For example, some pathogens cannot be grown in pure culture outside the host; because other pathogens grow only in humans, their study would require experimentation on people. The identification, isolation, and cloning of genes responsible for pathogen virulence have made possible a new molecular form of Koch’s postulates that resolve some of these difficulties. The emphasis is on the virulence genes present in the infectious agent rather than on the agent itself. The molecular postulates can be briefly summarized as follows:
- The virulence trait under study should be associated much more with pathogenic strains of the species than with non pathogenic strains.
- Inactivation of the gene or genes associated with the suspected virulence trait should substantially decrease pathogenicity.
- Replacement of the mutated gene with normal wild-type gene should fully restore pathogenicity.
- The gene should be expressed at some point during the infection and disease process.
- Antibodies or immune system cells directed against the gene products should protect the host.
The molecular approach cannot always be applied because of problems such as the lack of an appropriate animal system. It also is difficult to employ the molecular postulates when the pathogen is not well characterized genetically.
Reference: Microbiology Prescott.