Molecular Koch's postulates

Molecular Koch's postulates are a set of experimental criteria that must be satisfied to show that a gene found in a pathogenic microorganism encodes a product that contributes to the disease caused by the pathogen. Genes that satisfy molecular Koch's postulates are often referred to as virulence factors. The postulates were formulated by the microbiologist Stanley Falkow in 1988 and are based on Koch's postulates.^[1]

The postulates as originally described by Falkow are as follows:

1. "The phenotype or property under investigation should be associated with pathogenic members of a genus or pathogenic strains of a species." Additionally, the gene in question should be found in all pathogenic strains of the genus or species but be absent from nonpathogenic strains.
2. "Specific inactivation of the gene(s) associated with the suspected virulence trait should lead to a measurable loss in pathogenicity or virulence." Virulence of the microorganism with the inactivated gene must be less than that of the unaltered microorganism in an appropriate animal model.
3. "Reversion or allelic replacement of the mutated gene should lead to restoration of pathogenicity." In other words, reintroduction of the gene into the microbe should restore virulence in the animal model.

For many pathogenic microorganisms, it is not currently possible to apply molecular Koch's postulates to a gene in question. Testing a candidate virulence gene requires a relevant animal model of the disease being examined and the ability to genetically manipulate the microorganism that causes the disease. Suitable animal models are lacking for many important human diseases. Additionally, many pathogens cannot be manipulated genetically.

In 1996, Fredricks and Relman remarked on Falkow's postulates in their seminal paper on microbial pathogenesis.^[2] Their seven criteria have subsequently been accepted by most practitioners in the field.

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