Establishing the Cause of Infectious Disease

The fact that microorganisms and viruses cause infectious disease is now commonly accepted. The evidence that linked microbes to disease was discovered not much more than a century ago, however, when Robert Koch showed that that Bacillus anthracis causes anthrax (see A Glimpse of History). This was an important step forward, because it often allowed people to avoid or control infection. In addition, it led to the development of antimicrobial drugs and other therapies to combat infectious disease. From his experiments Koch formalized a set of criteria for determining the cause of infectious diseases; these criteria are known as Koch's Postulates. These are now supplemented and often supplanted by Molecular Postulates, which use precise genetic techniques to determine the pathogenicity of microorganisms and viruses.

Koch's Postulates

Robert Koch proposed that in order to conclude that a microbe causes a particular disease, these postulates must be fulfilled:

1. The microorganism must be present in every case of the disease.

2. The organism must be grown in pure culture from diseased hosts.

3. The same disease must be produced when a pure culture of the organism is introduced into susceptible hosts.

4. The organism must be recovered from the experimentally infected hosts.

Koch used these postulates to prove that Bacillus anthracis causes anthrax in sheep. He grew B. anthracis from all cases of anthrax tested; he introduced pure cultures of the organisms grown in the laboratory into healthy susceptible mice, again causing the disease anthrax; and finally, he recovered the organism from the experimentally infected mice.

It is important to note that there are many situations in which Koch's postulates cannot be carried out. In some cases the organism cannot be cultured in the laboratory. In other cases, it would not be ethical to test the postulates on humans because of safety concerns, and suitable experimental animal hosts are not available.

Molecular Postulates

A group of criteria for determining the cause of an infectious disease by using molecular techniques has been incorporated into a new set of postulates called the Molecular Postulates. These newer techniques deal directly with the virulence factors of microorganisms. These factors are particularly relevant in diseases such as pneumonia and urinary tract infection, which can be caused by a variety of microorganisms. They also help explain how some microbes such as Streptococcus pyogenes can cause a number of different diseases.

The Molecular Postulates state:

1. The virulence factor gene or its product should be found in pathogenic strains but not in non-pathogenic strains of the suspected pathogen.

2. Introduction of a cloned virulence gene should change a non-pathogenic to a pathogenic strain, whereas disrupting the function of the virulence gene should reduce the virulence of the organism.

3. The genes for virulence must be expressed during the disease process.

4. Antibodies or immune cells specific for the virulence gene products should be protective.

As with the traditional Koch's Postulates, it is not always possible to apply all of these postulates, but they provide many new approaches to determining the causative agents of infectious diseases. The genes in different strains of an organism are more important than the species in determining the pathogenic potential of that organism.

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