Donald A. Ferguson, Jr., Ph.D.
Associate Professor and Director of the Clinical Microbiology Laboratory
A.B. Biology ,Clark University ,
Worcester ,Massachusetts , 1967;
Ph.D. Microbiology ,Syracuse University ,
Syracuse ,New York , 1974
Research Associate , Anaerobe Laboratory of
Virginia Polytechnic Institute and State University ,Blacksburg ,Virginia (1975-78)
Assistant Professor of Microbiology (1978-89)
Associate Professor of Microbiology (1989-present)
Co-director of Clinical Microbiology Lab (1981-98)
Director of Clinical Microbiology Lab (1998-present),
Quillen College of Medicine, Johnson City ,TN.
Pathogenesis of bacterial infections including mixed anaerobic infections; virulence factors including: mechanisms of toxins, tissue tropism as mediated by specific colonization factors, adhesins and specific receptors; comparison and contrast of facultative intracellular (chronic) and extracellular (acute) bacterial infections and the roles of innate, humoral and cell-mediated immunity in their resolution; rationale for antibiotic treatment of bacterial infections.
Major Service Areas:
Director of the Clinical Microbiology Laboratory: The UPPG Diagnostic Microbiology Laboratory provides diagnostic microbiology services to all of the MEAC Clinical Departments and serves as a reference bacteriology laboratory for Johnson City Medical Center Hospital and Bristol Regional Medical Center Hospital . We also provide clinical laboratory training for Department of Internal Medicine residents, periodic laboratory update workshops for area county health care staff and physicians, and advanced diagnostic clinical microbiology training for physicians from around the world. We offer a laboratory rotation course for graduate students and a two week elective for senior medical students. We also have contributed our services and expertise to several NIH grants and have obtained numerous pharmaceutical grants for testing the efficacy of new antibiotics against clinical isolates from our laboratory.
OSHA Duties: I assure that OSHA standards are maintained for the handling of hazardous chemicals and blood-borne pathogens and oversee general laboratory safety in my capacity as OSHA Occupational Safety Officer and Infection Control Coordinator for the Department of Microbiology. I assure that all personnel evacuate the 3rd floor of building 119, VA Campus during a fire alarm in my capacity as Assistant Building Safety Coordinator.
Molecular Epidemiology of Helicobacter pylori Infections
Our research has dealt with delineating the transmission routes of Helicobacter pylori , the only known bacterium which is capable of colonizing and causing disease in the human stomach. It is the major cause of stomach ulcers, the almost exclusive cause of type B gastritis and duodenal ulcers and is statistically associated with gastric carcinoma and lymphoma. The bacterium is curved, micro- aerophilic , produces powerful urease and mucinase enzymes as virulence
factors and causes the most common bacterial infection of humans in the world. Despite numerous investigations over the decade in which the organism has been recognized as a pathogen, the route or routes of transmission have not been clearly established. We were the first to culture the organism from saliva. Our research group has produced exquisitely sensitive and specific DNA probes, and PCR-primers for detecting the organism in heavily contaminated sites such as saliva and feces. We have employed these in analytical methods such as Restriction Fragment Length Polymorphism (RFLP) and Single and Double-Stranded Conformational Polymorphism (SDSCP) to allow both detection and sub-typing of isolates from these and other sites without requiring culture and isolation of the organism. We have shown that the gastric string test is an excellent method for obtaining gastric juice for both cultural isolation of the organism and PCR detection of H. pylori DNA. This method allows asymptomatic patients to be tested for the presence of H. pylori in epidemiologic studies without having to undergo endoscopy .
Amelioration of Sepsis by Macrophage Activation
Sepsis, systemic inflammatory response syndrome (SIRS) and shock are significant causes of morbidity and mortality in critically ill patients. Clinical data indicate that (1->3)-ß- glucan phosphate reduces septic morbidity and mortality in surgical patients. Our research involves the investigation of the cellular and molecular mechanisms of glucan phosphate treatment in a mouse cecal ligation and puncture model of multi-microbial sepsis. My area of this study involves culture of blood from septic mice to determine the severity of bacteremia in glucan treated and non-treated animals. Blood is cultured for aerobic and anaerobic bacteria and the number of species of bacteria (especially anaerobic bacteria) isolated is correlated with the severity of the infection and the survival rate.
Innate Immune Recognition of Candida: Role of Cell Wall Glucans
Pathogenic fungi are increasingly common as opportunistic pathogens which cause significant morbidity and mortality in immunocompromised patients. It is not clear how fungal pathogens interact with the innate immune system to cause systemic infections. Glucans are the major carbohydrate constituents of fungal cell walls and may serve as important recognition signals for the innate immune system. My participation in this study involves growing Candida albicans to produce either blastospore or hyphal growth for extraction of cell wall glucans and for isolation of extracellular glucans which will then be characterized by NMR analysis. We plan to use the purified products to characterize the receptor mediated binding/internalization of Candida derived (1->3)-ß- glucans in human macrophage and neutrophil cell lines and determine whether the glucan receptor mediates the uptake and/or killing of Candida .We also plan to determine whether parenteral administration of highly purified Candida glucans stimulates tissue NF?B and NF-IL6 nuclear binding activity, a pro-inflammatory and/or chemokine response, alters T H1/T H2 cytokine profiles and whether Candida glucans will protect against challenge with viable Candida albicans .Our long-term objectives are to define the role of (1->3)-ß- glucans in the cellular and molecular pathogenesis of Candida infections and to utilize this data to identify potential drug targets and/or improve therapeutic strategies for the management of fungal infections.
The Effect of Dietary Supplementation with Glucan on immune function
Glucans are natural product polymers of glucose, which are produced by fungi, bacteria and plants. They have been shown to stimulate immunity and increase resistance to infectious challenge if administered via IV, IP, IM or SQ routes. Glucans are found as fiber in the normal diet and are components of traditional Chinese, Japanese and Indian medicines. Recently, dietary supplements have appeared in the western marketplace which claim to contain glucans . The manufacturers have inferred from the scientific literature that glucans have the same beneficial effects taken orally as has been observed with systemic administration. The evidence to support these claims, however, is limited and controversial. The aim of our research is to determine whether dietary supplementation with glucan will modulate immune function and increase resistance to common infectious diseases.
Rohrbach M., D.A. Ferguson, Jr. , J. Farnum , and E. Thomas. 1993. Chronic gastritis associated with Helicobacter pylori infection in southern Appalachian veterans with dyspepsia. So. Med. Journal 86 :1354-1359.
Wilhoite , S., D.A. Ferguson, Jr. , D. Soike , J. Kalbfleisch , and E. Thomas. 1993. Increased prevalence of Helicobacter pylori antibodies among nurses. Arch. Int. Med., 153 :708-712.
Ferguson , Jr., D.A. , C. Li , N.Patel , W.R. Mayberry, D.S. Chi and E. Thomas. 1993. Isolation of Helicobacter pylori from saliva. J. Clin .Microbiol . 31 :2802-2804.
Li, C., D.A. Ferguson, Jr. , T. Ha, D.S. Chi and E. Thomas. 1993. A highly specific and sensitive DNA probe derived from chromosomal DNA of Helicobacter pylori is useful for typing H. pylori isolates. J. Clin .Microbiol . 31 :2157-2162.
Li, C., T. Ha, D.A. Ferguson, Jr. , P.R. Musich , D.S. Chi and E. Thomas. 1995. High prevalence of Helicobacter pylori in saliva demonstrated by a novel PCR assay. J. Clin .Pathol .48 : 662-667.
Gallemore , G.H., R.T. Mohon , and D.A. Ferguson, Jr. 1995. Lactobacillus fermentum endocarditisinvolving a native mitral valve. J. Tenn. Med. Assoc 88 : 306-308.
Li, C., T. Ha, D.A. Ferguson, Jr. , D.S. Chi, R. Zhao, N. R. Patel, K. Guha and E. Thomas. 1996. A newly developed pcr assay of H. pylori in gastric biopsy, saliva, and feces: evidence of high prevalence of H. pylori in saliva supports oral transmission. Digestive Diseases and Sciences 41 : 2142-2149.
Reddy, I. , D.A. Ferguson, Jr. and F.A. Sarubbi .1997. Endocarditis due to Actinomyces pyogenes .Clin .Infect. Dis. 25 :1476-1477.
Li, C., T. Ha, D.S. Chi, D.A. Ferguson, Jr. , C. Jiang , J.J. Laffan, and E. Thomas. 1997. Differentiation of Helicobacter pylori strains directly from gastric biopsy specimens by pcr -based restriction fragment length polymorphism analysis without culture. J. Clin .Microbiol . 35 (12): 3021-3025.
Thomas, E., C. Jiang , D.S. Chi, C. Li, and D.A. Ferguson, Jr. 1997. The role of the oral cavity in Helicobacter pylori infection. Amer. J. Gastroenterol . 92: 2148-2154.
Jiang , C., C. Li, T. HA, D.A. Ferguson, Jr. , D.S. Chi, J. Laffan and E. Thomas. 1998. Identification of H. pylori in saliva by a nested PCR assay derived from a newly cloned DNA probe. Dig. Dis. Sci. 43: 1211-1218.
Vasques , J.E., D.A. Ferguson, Jr. , S. Bin- Sagheer , J.W. Myers, A. Ramsak , M.A. Wilson and F.A. Sarubbi .1998. Pasteurella multocida endocarditis: a molecular epidemiology study. Clin .Infect Dis. 26 :518-520
Jiang , C., C. Li, D.S. Chi, D.A. Ferguson, Jr. , T. Ha, J.J. Laffan, and E. Thomas. 1998. Combination of single- and double-stranded conformational polymorphism for direct discrimination of gastric Helicobacter pylori . J Microbiol Methods 34: 1-8.
Ferguson , Jr., D.A. , C. Jiang , J.J. Laffan, C. Li, D.S. Chi and E. Thomas. 1999. Evaluation of two string tests for obtaining gastric juice for culture, nested- pcr detection and combined single- and double-stranded conformational polymorphism discrimination of Helicobacter pylori . Dig Dis Sci 44: 2056-2062
Williams, David L., T. Ha, C. Li, J.H. Kalbfleisch and D. A. Ferguson, Jr. 1999. Early activation of hepatic NF?B and NF-IL6 in polymicrobial sepsis correlates with bacteremia, cytokine expression and mortality. Annals of Surgery 230: 95- 104.
Browder , W. T. Ha, C. Li, J.H. Kalbfleisch , D.A. Ferguson, Jr. and D. Williams. 1999. Early activation of pulmonary NF?B and NF-IL6 in polymicrobial sepsis. J Trauma 46 : 590-596.
Williams, David L., T. Ha, C. Li, J.H. Kalbfleisch , J.J. Laffan and D. A. Ferguson, Jr. 1999. Inhibiting early activation of tissue NF?B and NF-IL6 with (1->3)-ß-D- glucan increases long term survival in polymicrobial sepsis. Surgery 126: 54-65.