Correspondence

Bacteria Associated with Bacterial Vaginosis

N Engl J Med 2006; 354:202-203January 12, 2006

Article

To the Editor:

Fredricks and colleagues (Nov. 3 issue)1 reported complex communities of bacteria and a high level of species diversity in vaginal secretions from women with bacterial vaginosis. However, the study of vaginal fluid alone provides an incomplete picture of disease pathogenesis, since infections also may affect the vaginal epithelium. Fluorescence in situ hybridization of vaginal-biopsy specimens with the use of bacteria-specific probes demonstrates that a clinical diagnosis of bacterial vaginosis is highly associated with the development of a bacterial biofilm on the epithelial surface.2 Gardnerella and atopobium species together constitute more than 90 percent of the biofilm mass. The biofilm also contains numerous, less abundant bacterial species, in agreement with the findings of Fredricks and others.1,3 Formation of the biofilm allows bacteria to reach higher concentrations than can be achieved in vaginal fluid alone. Desquamation of epithelial cells coated with biofilm in situ results in the clue cells that are diagnostic of bacterial vaginosis. Given such complex microbiota, it is clear that identification of single pathogens, as was introduced by Koch and Pasteur more than 100 years ago, is inadequate for explaining the pathogenesis of bacterial vaginosis.

Laura P. Hale, M.D., Ph.D.
Duke University Medical Center, Durham, NC 27710
laura.hale@duke.edu

Alexander Swidsinski, M.D., Ph.D.
Charité Hospital of Humboldt University, 10098 Berlin, Germany

Werner Mendling, M.D.
Vivantes Clinic for Obstetrics and Gynecology, 10967 Berlin, Germany

3 References

1. 1

   Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 2005;353:1899-1911
   Full Text | Web of Science | Medline

2. 2

   Swidsinski A, Mendling W, Loening-Baucke V, et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol 2005;106:1013-1023
   CrossRef | Web of Science | Medline

3. 3

   Verhelst R, Verstraelen H, Claeys G, et al. Cloning of 16S rRNA genes amplified from normal and disturbed vaginal microflora suggests a strong association between Atopobium vaginae, Gardnerella vaginalis and bacterial vaginosis. BMC Microbiol 2004;4:16-16
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Hale and colleagues highlight their study showing that adherent bacterial biofilms commonly were detected in vaginal-biopsy specimens from subjects with bacterial vaginosis, suggesting that biofilms may play a role in the pathophysiology of this syndrome.1 We agree that it is important to study both the vaginal epithelial surface and free vaginal fluid to determine how bacterial communities may lead to disease. Fluorescence in situ hybridization is an excellent method for studying the spatial relationships and composition of bacteria in these compartments. We also agree that no single bacterium is likely to be the cause of bacterial vaginosis and that Koch's postulates for disease causation are inadequate for describing potential causal relationships in this syndrome. Bacterial vaginosis probably results from infection with complex communities of bacteria that consist of metabolically interdependent (syntrophic) species. Diseases caused by uncultivated microbes or communities of microbes are not amenable to the application of Koch's postulates in their original formulation2); therefore, we must build a case for causation on the basis of a concordance of scientific evidence.3

David N. Fredricks, M.D.
Fred Hutchinson Cancer Research Center, Seattle, WA 98109
dfredric@fhcrc.org

Jeanne M. Marrazzo, M.D., M.P.H.
University of Washington, Seattle, WA 98195

3 References

1. 1

   Swidsinski A, Mendling W, Loening-Baucke V, et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol 2005;106:1013-1023
   CrossRef | Web of Science | Medline

2. 2

   Evans AS. Causation and disease: a chronological journey. New York: Plenum Medical Book, 1993:238.
   

3. 3

   Fredricks DN, Relman DA. Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates. Clin Microbiol Rev 1996;9:18-33
   Web of Science | Medline

Citing Articles (4)

Citing Articles

1. 1

   Piet Cools, Hans Verstraelen, Mario Vaneechoutte, Rita Verhelst. 2011. Atopobium. , 31-43.
   CrossRef

2. 2

   RF Lamont, JD Sobel, RA Akins, SS Hassan, T Chaiworapongsa, JP Kusanovic, R Romero. (2011) The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG: An International Journal of Obstetrics & Gynaecology 118:5, 533-549
   CrossRef

3. 3

   P. CADIEUX, G. WIGNALL, R. CARRIVEAU. 2009. Introduction to biofilms in urology. , 3-41.
   CrossRef

4. 4

   Prabodh K. Gupta, Cindy McGrath. 2008. Microbiology, Inflammation, and Viral infections. , 91-129.
   CrossRef