Microbes and disease Microbes and Disease: Establishing a Connection History and Relevance of Koch's Postulates And The Germ Theory of Infectious Disease The first sightings of microbes through the microscopes invented by Antonie van Leeuwenhoek ( ) occurred in the 1600s, but it took 2 centuries for the connection between microbes and disease to be made.

Koch's Postulates A German microbiologist, Robert Koch ( ), proposed a set of "rules" for establishing a connection between a microbe and a disease; 1.The microbe must be associated with symptoms of the disease and must be present at the site of infection. 2.The microbe must be isolated from the lesions of disease and grown as a pure culture. 3.A pure culture of the microbe, when inoculated into a susceptible host, must reproduce the disease in the experimental host. 4.The microbe must be reisolated in pure culture from the experimentally infected host.

Some Important Limitations of The Koch's Postulates. First, they assume that the disease symptoms are dependent entirely on the bacterium, yet host susceptibility due to genetic and other factors, such as age and the proficiency of the immune system, varies in human and animal populations and is now known to play a major role in virulence

In addition, prior infection with one microbe may influence the response of the host to subsequent infection with another microbe. 2. Second, Koch's postulates assume that a pathogenic bacterium can be readily isolated and cultured. Unfortunately, not all bacteria can be cultured (or at least we have not yet determined how to culture them) under standard laboratory conditions. 3. Third, Koch's postulates assume that all members of a bacterial species are equally virulent and that a single species causes each disease. This is clearly not the case for all bacterial pathogens.

Koch's postulates require reinoculation into a susceptible host to reproduce the disease symptoms. For human disease, this requires either brave volunteers in highly structured studies or, more likely, a good animal model. However, an animal model may not be available, and indeed, for many diseases non- human animals are only approximate model systems.

Limitations of Artificial Inoculation of Microbe into a Susceptible Host In recent years, the third postulate has been a stumbling block for scientists working on H. pylori and C. pneumoniae. Acceptance of the proposal that most ulcers are caused by bacteria was held up for more than a decade because critics of the idea insisted that Koch's third postulate had to be met. There are now good animal models for ulcers, but in the early days of H. pylori research, these models were not available. This led one frustrated scientist to use himself as the "guinea pig" in an attempt to satisfy Koch's third postulate.

Modern Alternatives to Detecting and Culturing Microbe A modern alternative to detecting and cultivating pathogenic bacteria in diseased tissues is to use molecular biology approaches, such as the PCR-based typing approaches

Concepts of Disease Varieties of Human-Microbe Interactions 1) Scientists realized that not all people who drank water containing Vibrio cholerae developed cholera. (2) Not all people exposed to someone with tuberculosis developed symptomatic disease, even though it could be shown that they were infected with the bacterium.

Molecular Approaches to Study Disease- Causing Microbe Molecular Koch's Postulates There have been several versions of molecular Koch's postulates, but most of them read as follows: 1.First, the gene (or its product) should be found only in strains of bacteria that cause the disease and not in bacteria that are avirulent. 2.Second, the gene should be "isolated" by cloning. 3.Third, disrupting the gene in a virulent strain should reduce or attenuate its virulence (the concept of attenuation). Alternatively, introducing the cloned gene into an avirulent strain should render the strain virulent. 4.Finally, it should be demonstrated that the gene is expressed by the bacterium when it is in an animal or human volunteer at some point during the infectious process.