Molecular Microbiology of Human-Associated Niches

David Fredricks, MD

Our understanding of the microflora that colonize the human body is derived mostly from studies using cultivation methods to detect and identify microorganisms.  The limitations of cultivation technology are increasingly apparent since many newly described microbial species defy attempts at laboratory propagation.  An alternative approach for characterizing microbial communities is to identify the microbial constituents through their unique ribosomal RNA gene sequences. We use this cultivation-independent molecular method to analyze the census of microbes present in human-associated niches, such as the vagina.  We are studying the syndrome bacterial vaginosis and have identified several new uncultivated bacterial species associated with this syndrome. We are interested in studying the role of novel microbial communities in the maintenance of human health and the production of disease.

We previously used molecular methods such as consensus sequence rDNA PCR and fluorescence in situ hybridization (FISH) to identify enigmatic pathogens and to localize these microbes to specific regions of infected tissue. For instance, we used FISH to identify the site of replication of the cultivation-resistant Whipple bacillus (Tropheryma whipplei ) in infected small intestine from patients with Whipple disease.   We used molecular phylogenetic analysis to identify the causative agent of rhinosporidiosis (Rhinosporidium seeberi) as a protistan parasite from a novel clade of microbes near the animal-fungal divergence.   We are interested in employing similar techniques to identify novel pathogens that may be responsible for some unexplained disease syndromes.

Publications:

Fredricks DN, Fiedler TL, Thomas KK, Oakley BB, Marrazzo JM.  Targeted Polymerase Chain Reaction for the Detection of Vaginal Bacteria Associated with Bacterial Vaginosis.  Journal of Clinical Microbiology 2007; 45:3270-6.

Fredricks DN , Fiedler T, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis.   New England Journal of Medicine 2005; 353:1899-1911.

Fredricks DN , Marrazzo JM. Molecular methodology in determining vaginal flora in health and disease; its time has come. Current Infectious Diseases Reports 2005;7:463-470.

Fredricks DN , Schubert MM, Myerson D. Molecular identification of an invasive gingival bacterial community. Clinical Infectious Diseases 2005;41:e1-4.

Fredricks DN , Myerson D.   Pneumonia in a patient with leukemia .   Infectious Diseases in Clinical Practice 2006; In press.

Fredricks DN. Diseases of unknown etiology: the role of infectious agents. In: Infectious Diseases.   Editors: Cohen J, Powderly WJ.   Second edition.   Elsevier Health Sciences, London, 2003.

Fredricks DN , Relman DA.   Localization of Tropheryma whippelii rRNA in tissues from patients with Whipple's disease.   Journal of Infectious Diseases 2001;183:1229-1237.

Maiwald M, von Herbay A, Persing DH, Mitchell PS, Abdelmalek MF, Thorvilson JN, Fredricks DN , Relman DA.   Tropheryma whippelii DNA is rare in the intestinal mucosa of patients without other evidence of Whipple's disease.   Annals of Internal Medicine 2001;134:115-119.

Fredricks DN , Jolley J, Lepp PW, Kosek J, Relman DA.   Rhinosporidium seeberi : A   human pathogen from a novel group of aquatic protistan parasites.   Emerging Infectious Diseases 2000; 6: 273-282.

Fredricks DN , Relman DA.   Infectious agents and the etiology of chronic idiopathic diseases.  Current Clinical Topics in Infectious Diseases 1998; 18:180-200.

Fredricks DN , Relman DA.   Cultivation of Whipple bacillus: the irony and the ecstasy. Lancet   1997; 350:1262-1263.

Fredricks DN , Relman DA.   Sequence-based identification of microbial pathogens: a   reconsideration of Koch's postulates. Clinical Microbiology Reviews 1996; 9: 18-33.