Molecular Koch's postulates are a set of experimental criteria that must be satisfied to show that a
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
found in a pathogenic
microorganism
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
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
Virulence factors (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the followin ...
. The postulates were formulated by the microbiologist
Stanley Falkow
Stanley "Stan" Falkow (January 24, 1934 – May 5, 2018) was an American microbiologist and a professor of microbiology at Georgetown University, University of Washington, and Stanford University School of Medicine. Falkow is known as the father ...
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...
or property under investigation should be associated with pathogenic members of a genus or pathogenic strains of a
species
In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
.
# Specific inactivation of the gene(s) associated with the suspected
virulence
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
trait should lead to a measurable loss in pathogenicity or
virulence
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
.
# Reversion or allelic replacement of the mutated gene should lead to restoration of pathogenicity."
To apply the molecular Koch's postulates to human diseases, researchers must identify which microbial genes are potentially responsible for symptoms of pathogenicity, often by sequencing the full genome to compare which nucleotides are homologous to the protein-coding genes of other species. Alternatively, scientists can identify which mRNA transcripts are at elevated levels in the diseased organs of infected hosts. Additionally, the tester must identify and methods for inactivating and reactivating the gene being studied.
In 1996, Fredricks and Relman proposed seven molecular guidelines for establishing microbial disease causation:{{cite journal , last1=Fredricks , first1=David , last2=Relman , first2=David , title=Sequence-Based Identification of Microbial Pathogens: a Reconsideration of Koch's Postulates , journal=Clinical Microbiology Reviews , date=January 1996 , volume=9 , issue=1 , pages=18-33 , doi=10.1128/CMR.9.1.18 , url= , pmid=8665474 , pmc=172879
# "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 (i.e., with anatomic, histologic, chemical, or clinical evidence of pathology) and not in those organs that lack pathology.
# Fewer, or no, copy numbers of pathogen-associated nucleic acid sequences should occur in hosts or tissues without disease.
# With resolution of disease (for example, with clinically effective treatment), the copy number of pathogen-associated nucleic acid sequences should decrease or become undetectable. With clinical relapse, the opposite should occur.
# 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.
# The nature of the microorganism inferred from the available sequence should be consistent with the known biological characteristics of that group of organisms. When phenotypes (e.g., pathology, microbial morphology, and clinical features) are predicted by sequence-based phylogenetic relationships, the meaningfulness of the sequence is enhanced.
# 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.
# These sequence-based forms of evidence for microbial causation should be reproducible."