ZFIN ID: ZDB-PUB-200221-11
Mycobacterium tuberculosis pathogenicity viewed through the lens of molecular Koch's postulates
Ramakrishnan, L.
Date: 2020
Source: Current opinion in microbiology   54: 103-110 (Review)
Registered Authors: Ramakrishnan, Lalita
Keywords: none
MeSH Terms:
  • Animals
  • Disease Models, Animal
  • Genes, Bacterial
  • Host-Pathogen Interactions
  • Humans
  • Macrophages, Alveolar/immunology
  • Macrophages, Alveolar/microbiology
  • Mycobacterium Infections, Nontuberculous/immunology
  • Mycobacterium Infections, Nontuberculous/microbiology*
  • Mycobacterium marinum/genetics*
  • Mycobacterium marinum/pathogenicity*
  • Mycobacterium marinum/physiology
  • Mycobacterium tuberculosis/genetics*
  • Mycobacterium tuberculosis/pathogenicity*
  • Mycobacterium tuberculosis/physiology
  • Tuberculosis/immunology
  • Tuberculosis/microbiology*
  • Virulence/genetics
  • Virulence Factors/genetics
  • Virulence Factors/physiology*
  • Zebrafish
PubMed: 32062573 Full text @ Curr. Opin. Microbiol.
Thirty years ago Stanley Falkow formulated molecular Koch's postulates as a framework to help dissect the contribution of microbial genes to their pathogenicity (Box 1). Three years later, his advice led me to develop Mycobacterium marinum, a close genetic relative of Mycobacterium tuberculosis, as a model for tuberculosis pathogenesis. Here, I discuss insights into M. tuberculosis pathogenicity from studying M. marinum in the zebrafish, and frame them in terms of molecular Koch's postulates. The highly orchestrated life cycle of M. tuberculosis is achieved in substantial measure not by "traditional" pathogen-exclusive virulence genes acquired along its evolutionary history, but rather by genes that are shared with its environmental ancestors. Together, these genes support its tactics of subterfuge and exploitation to overcome host immunity so as to produce the transmissible disease that ensures the evolutionary survival of this obligate human pathogen.