Microbial pathogenesis

Postulates for the detection of microbial pathogens

In 1996, Fredricks and Relman suggested the following postulates for the novel field of microbial pathogenesis.

1. (i) A nucleic acid sequence belonging to a putative pathogen should be present in most cases of an infectious disease. Microbial nucleic acids should be found preferentially in those organs or gross anatomic sites known to be diseased, and not in those organs that lack pathology.
2. (ii) Fewer, or no, copies of pathogen-associated nucleic acid sequences should occur in hosts or tissues without disease.
3. (iii) With resolution of disease, the copy number of pathogen-associated nucleic acid sequences should decrease or become undetectable. With clinical relapse, the opposite should occur.
4. (iv) When sequence detection predates disease, or sequence copy number correlates with severity of disease or pathology, the sequence-disease association is more likely to be a causal relationship.
5. (v) The nature of the microorganism inferred from the available sequence should be consistent with the known biological characteristics of that group of organisms.
6. (vi) Tissue-sequence correlates should be sought at the cellular level: efforts should be made to demonstrate specific in situ hybridization of microbial sequence to areas of tissue pathology and to visible microorganisms or to areas where microorganisms are presumed to be located.
7. (vii) These sequence-based forms of evidence for microbial causation should be reproducible.