Pathogen Discovery and Identification: The Role of Novel Microbes in Unexplained Diseases

David Fredricks, MD

Analysis of microbial small subunit ribosomal RNA gene sequences amplified from infected tissues has been successfully used to identify and characterize cultivation-resistant pathogens such as Tropheryma whippelii , the bacterium that causes Whipple's disease, and Rhinosporidium seeberi , the protistan parasite that causes rhinosporidiosis.    In addition, labeling microbial rRNA with fluorescent DNA probes has allowed us to visualize these organisms in tissue sections via fluorescence microscopy. We are interested in employing similar techniques to identify novel pathogens that may be responsible for some unexplained disease syndromes, such as idiopathic pneumonia in hematopoietic cell transplant recipients.

Publications:

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 . Novel microbes and chronic diseases.   Clinical Microbiology Newsletter 2002;24:41-44.

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.

Lynch T, Odel J, Fredricks DN , Louis ED, Forman S, Rotterdam H, Fahn S, Relman DA.   Polymerase chain reaction-based detection of Tropheryma whippelii   in central nervous system Whipple's disease.   Ann Neurol 1997; 42: 120-24.

Ramzan NN, Loftus E, Burgart LJ, Rooney M, Batts KP, Wiesner RH, Fredricks DN , Relman DA, Persing DH. Diagnosis and monitoring of Whipple's disease by polymerase chain reaction. Ann Intern Med 1997;126(7):520-7.

Petrides PE, Muller-Hocker J, Fredricks DN , Relman DA. PCR analysis of T. whippelii DNA in a case of Whipple's disease: effect of antibiotics and correlation with histology. American Journal of Gastroenterology   1998 Sep, 93(9):1579-82.