Molecular Koch's Postulates
Although the criteria that Koch developed for proving a causal relationship
between and a microorganism and a specific disease
have been of immense 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 resolves 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:
1. The virulence trait under study should be associated much more with
pathogenic strains of the species than with non pathogenic strains.
2. Inactivation of the gene or genes associated with the suspected
virulence trait should substantially decrease pathogenicity.
3. Replacement of the mutated gene with the normal wild-type gene
should fully restore pathogenicity.
4. The gene should be expressed at some point during the infection
and disease process.
5. 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.