The necessity to revise Koch’s postulates and its application to infectious and non-infectious diseases: a mini-review


Advances in the science have promoted all aspects of human’s life; these, in turn, have changed many principles and scientific postulates. Koch’s postulates, since the beginning of their implementation, have been one of the important subjects involving complications and misinterpretations regarding the causal relationship of microbe-hosts. These postulates have been shown not to be correct in some cases including the inability of some microbes to grow in the culture medium, viruses, or anaerobic bacteria. Today, due to some new scientific facts like the social behaviors of bacteria, such as quorum sensing, there are serious problems regarding the definition of whole microbial effects; these include microbiomes and viromes, as well as their interaction with the existing eukaryotics, the complicated relations between bacteria, L-forms, and cell wall–deficient bacteria, and the important role of microbes in the development of non-infectious diseases. So, the application of Koch’s postulates to explain the causal relationships between host-microbes could be difficult. Therefore, nowadays, even the molecular Koch’s postulates are not accountable. Also, according to the new scientific discoveries, various criteria such as changes in the immune system, pathology, and clinical findings, along with the results of daily laboratory tests, should be used to apply Koch’s postulates in the etiologic studies. Otherwise, the possible etiologic relationships between the host-microbes cannot be verified due to numerous complications; certainly, the relationship between the doctor and the lab is ultimately weakened. Therefore, public health, prevention, and much of the antimicrobial treatments will also remain in a state of ambiguity.

This is a preview of subscription content, log in to check access.

Fig. 1


  1. 1.

    Antonelli G, Cutler S (2016) Evolution of the Koch postulates: towards a 21st-century understanding of microbial infection. Clin Microbiol Infect 22(7):583–584

    CAS  Article  Google Scholar 

  2. 2.

    Methé BA, Nelson KE, Pop M, Creasy HH, Giglio MG, Huttenhower C, Gevers D, Petrosino JF, Abubucker S, Badger JH (2012) A framework for human microbiome research. Nature 486(7402):215

    Article  Google Scholar 

  3. 3.

    Astrauskiene D, Bernotiene E (2007) New insights into bacterial persistence in reactive arthritis. Clin Exp Rheumatol 25(3):470–479

    CAS  PubMed  Google Scholar 

  4. 4.

    Errington J, Mickiewicz K, Kawai Y, Wu LJ (2016) L-form bacteria, chronic diseases and the origins of life. Philosophical Transactions of the Royal Society B: Biological Sciences 371(1707):20150494

    Article  Google Scholar 

  5. 5.

    Pohlod DJ, Mattman LH, Tunstall L (1972) Structures suggesting cell-wall-deficient forms detected in circulating erythrocytes by fluorochrome staining. Appl Environ Microbiol 23(2):262–267

    CAS  Article  Google Scholar 

  6. 6.

    Kar S, Basu S, Sharma S, Das T (2011) Endogenous endophthalmitis caused by bacteria with unusual morphology in direct microscopic examination of the vitreous. Indian J Ophthalmol 59(4):329

    Article  Google Scholar 

  7. 7.

    Lorian V, Waluschka A, Kim Y (1982) Abnormal morphology of bacteria in the sputa of patients treated with antibiotics. J Clin Microbiol 16(2):382–386

    CAS  Article  Google Scholar 

  8. 8.

    Mani R, Nagarathna S, Chandramuki A (2008) Abnormal morphology of bacteria in the cerebrospinal fluid of a patient on antibiotics. Indian J Med Microbiol 26(3):283

    CAS  Article  Google Scholar 

  9. 9.

    Middleton J, Chmel H (1978) Aberrant form of Pseudomonas aeruginosa in sputum and cerebrospinal fluid causing infection in a compromised patient. J Clin Pathol 31(4):351–354

    CAS  Article  Google Scholar 

  10. 10.

    Onwuamaegbu M, Belcher R, Soare C (2005) Cell wall-deficient bacteria as a cause of infections: a review of the clinical significance. J Int Med Res 33(1):1–20

    CAS  Article  Google Scholar 

  11. 11.

    Casadesús J (2007) Bacterial L-forms require peptidoglycan synthesis for cell division. Bioessays 29(12):1189–1191

    Article  Google Scholar 

  12. 12.

    McLaughlin RW, Vali H, Lau PC, Palfree RG, De Ciccio A, Sirois M, Ahmad D, Villemur R, Desrosiers M, Chan EC (2002) Are there naturally occurring pleomorphic bacteria in the blood of healthy humans? J Clin Microbiol 40(12):4771–4775

    Article  Google Scholar 

  13. 13.

    Panaiotov S, Filevski G, Equestre M, Nikolova E, Kalfin R (2018) Cultural isolation and characteristics of the blood microbiome of healthy individuals. Advances in Microbiology 8(05):406

    CAS  Article  Google Scholar 

  14. 14.

    Potgieter M, Bester J, Kell DB, Pretorius E (2015) The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol Rev 39(4):567–591

    Article  Google Scholar 

  15. 15.

    Gholizadeh P, Mahallei M, Pormohammad A, Varshochi M, Ganbarov K, Zeinalzadeh E, Kafil H (2019) Microbial balance in the intestinal microbiota and its association with diabetes, obesity and allergic disease. Microb Pathog 127:48–55

    Article  Google Scholar 

  16. 16.

    Hall-Stoodley L, Stoodley P, Kathju S, Høiby N, Moser C, William Costerton J, Moter A, Bjarnsholt T (2012) Towards diagnostic guidelines for biofilm-associated infections. FEMS Immunol Med Microbiol 65(2):127–145

    CAS  Article  Google Scholar 

  17. 17.

    Potera C (1999) Forging a link between biofilms and disease. American Association for the Advancement of Science

  18. 18.

    Wolcott R, Dowd S (2011) The role of biofilms: are we hitting the right target? Plast Reconstr Surg 127:28S–35S

    CAS  Article  Google Scholar 

  19. 19.

    Rhoads DD, Wolcott RD, Sun Y, Dowd SE (2012) Comparison of culture and molecular identification of bacteria in chronic wounds. Int J Mol Sci 13(3):2535–2550

    CAS  Article  Google Scholar 

  20. 20.

    Ehrlich GD, Arciola CR (2012) From Koch’s postulates to biofilm theory. The lesson of Bill Costerton. SAGE Publications Sage UK, London, England

    Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Pourya Gholizadeh.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This is a literature review study and therefore, ethical approval was not required.

Informed consent

For this type of study, formal consent was not required.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hosainzadegan, H., Khalilov, R. & Gholizadeh, P. The necessity to revise Koch’s postulates and its application to infectious and non-infectious diseases: a mini-review. Eur J Clin Microbiol Infect Dis 39, 215–218 (2020).

Download citation


  • Koch’s postulates
  • Interpretation
  • L-form
  • Biofilm