Koch’s Postulates for 21st Century

Robert Koch formulated his theories in the 19th century on the establishment of a causal link between a microbe and a disease. Since the development of Koch postulates till the present day, the issue of infectious agent attribution has plagued microbiologists. 

Scientific discoveries have improved every element of human life, which has led to the modification of numerous scientific postulates and tenets. Even Robert Koch acknowledged that his suggested guidelines for determining causation for microbial illnesses might have some exceptions. These days, a reevaluation of the initial hypotheses is necessary due to the growing dependence on sequence-based techniques for microbiological identification.

Due to recent scientific discoveries, it may now be challenging to apply Koch's postulates to explain host-microbe causal linkages, such as those involving quorum sensing, microbiomes, viromes and their interactions with eukaryotic organisms. Considering this, Koch's postulates have been updated to the molecular level in more recent times to take into account developments in experimentation and a deeper comprehension of the host-parasite connection. 

The most significant technological shifts of the twenty-first century are the increasing use of big sequencing datasets in research practice. These modern research methodologies are gaining traction and developing into ever more creative ways to use sequencing data to identify intricate behavioural patterns and get a better comprehension of the bacterial cell. This technology has increased the pressure for the advancement of molecular Koch's postulates to next generation postulates.

The first postulate, which states that bacterial strains with an identifiable genetic mutation should exhibit the desired phenotype, will typically be easily fulfilled by genomic screening techniques. The second postulate states that particular modifications to the gene of interest ought to alter the relevant phenotype. Although not every genetic variation will lead to a loss of gene function, one common method to satisfy this postulate is to create targeted gene deletions and replicate the experimental setup that produces the desired phenotype. CRISPR is a well-known example of sequence-specific suppression of gene expression.The third and final postulate focuses on using genetic complementation to restore the observed phenotype. In order to complete the circle and establish causation, this crucial stage might call for a more advanced collection of genetic instruments. Complementation through a conditional expression system, typically on a plasmid or at an ectopic locus in the genome, is the most obvious example. 

Microbiology is now more equipped than ever to promote a greater understanding of the natural world through critical analysis of present microbiology practice and a renewed understanding of the importance of sharing complex datasets across disciplines. The emergence of the field of virology verified that strict adherence to the standards proposed by Koch was insufficient. With the advent of whole-genome sequencing, additional modifications to causality standards are necessary.

References

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2. Falkow S. Molecular Koch's postulates applied to bacterial pathogenicity--a personal recollection 15 years later. Nat Rev Microbiol. 2004;2(1):67–72.

3. Fredricks DN, Relman DA. Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates. Clin Microbiol Rev. 1996 Jan;9(1):18-33. 

4. Kobras et al. Next-generation microbiology: from comparative genomics to gene function. Genome Biology 2021;22:123.  

5. G. Antonelli, S. Cutler. Evolution of the Koch postulates: towards a 21st-century understanding of microbial infection. Clinical Microbiology and Infection 2016; 22(7):583-534.