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 nonpathogenic strains. Box 1.2 Molecular Koch’s Postulates

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.

Eilshemius Hesse, the wife of Walther Hesse, one of Koch’s assistants . She suggested the use of agar as a solidifying agent—she had been using it successfully to make jellies for some time. Agar was not attacked by most bacteria and did not melt until reaching a temperature of 100°C. One of Koch’s assistants, Richard Petri, developed the petri dish , a container for solid culture media. These developments made possible the isolation of pure cultures that contained only one type of bacterium, and directly stimulated progress in all areas of bacteriology. Isolation of bacteria and pure culture techniques .

Koch also developed mediasuitable for growing bacteria isolated from the body. Because of their similarity to body fluids, meat extracts and protein digests were used as nutrient sources. The result was the development of nutrient broth and nutrient agar, media that are still in wide use today. By 1882 Koch had used these techniques to isolate the bacillus that caused tuberculosis. There followed a golden age of about 30 to 40 years in which most of the major bacterial pathogens were isolated