
![]() |
Douglas E. BergProfessorPhone, office: (314)-362-2772 Phone, lab: (314)-362-2771 FAX: (314)-362-1232 email: berg@borcim.wustl.edu 8220 McDonnell Pediatric Research Building |
We study Helicobacter pylori (Hp), a genetically diverse species that chronically infects the gastric mucosa of billions of people worldwide. It constitutes a major cause of peptic ulcers and gastric cancer, even though most infections are asymptomatic. Infections seem poised on a “knife edge”, always provoking some inflammation, which provides nutrients for bacterial growth while being insufficient for pathogen clearance. The following three projects illustrate our current research directions.
1) Hp population genetics. Our analysis of housekeeping gene sequences of Hp from different human populations showed that East Asian and Spanish strains are distinct, whereas strains from urban Peruvian Amerindians (collected by collaborator Dr. Robert Gilman) are mostly Spanish-like, whereas strains from a remote Amazonian population are Asian-like. Perhaps Hp brought to the Americas by European conquerors were more robust than ancestral Amerindian strains, and outcompeted them during mixed infection.
2) Interplay with host. We found that many Hp strains can infect mice, and that “specialist” Hp strains can infect some inbred mouse lines (e.g., DBA/2) far better than others (e.g. BALB/c). Certain pairs of mouse-colonizing H. pylori strains differ in preferred sites of stomach colonization, and thus can coexist during chronic infection. Among strains that do not differ in gastric tropism, some are more vigorous than others. This mouse infection model should allow experimental tests of interpretations gleaned from human population studies (1, above). Selection and analysis of increased-vigor or expanded-host-range Hp mutants or recombinants should allow definition of bacterial factors important in vivo.
3) Evolution in real time. In collaboration with Dr. Tom Albert, we implemented a very efficient microarray-hybridization method for finding point mutations anywhere in a bacterial genome. Using this and new genetic analysis strategies, we are analyzing mutations in the multiple genes that allow stepwise emergence of high level resistance to the important anti-Hp agent metronidazole (Mtz). Many of these mutations diminish the ability of cells to convert Mtz from prodrug to bactericidal agent (chemical reduction). One special class alters Hp’s novel “Fur” [iron and pH responsive] regulatory protein. These analyses should give valuable insights into protein structure-function and regulatory circuitry, serve as a general model for studies and understanding of complex, important genetic traits, with implications for the new discipline of “systems biology”.
| Date and place of birth: September 21, 1943; Mt. Vernon, New York Citizenship: U.S.A. | |
Education | |
| 1964 | B.S. Botany, Cornell University, Ithaca, New York |
| 1969 | Ph.D. Genetics, University of Washington, Seattle |
Professional Experience and Appointments | |
| 1991-Present | Alumni Endowed Professor of Molecular Microbiology Professor of Genetics, and Professor of Medicine Washington University School of Medicine. St. Louis, Missouri, 63110 |
| 1964-1969 | Graduate Fellow and Teaching Assistant (Genetics), University of Washington (with Dr. Jonathan A. Gallant) Thesis: Berg, D. E. 1969. Recombinant formation in partially diploid strains of Escherichia coli. Ph.D. dissertation, University of Washington. |
| 1969-1971 | USPHS Postdoctoral Fellow, Stanford University Medical School, Department of Biochemistry (with Dr. A. Dale Kaiser). |
| 1971-1975 | Research Associate, University of Geneva, Department of Molecular Biology (with Dr. Lucien G. Caro). |
| 1975-1977 | Research Associate, University of Wisconsin, Department of Biochemistry (with Dr. Julian Davies). |
| 1977-1981 | Assistant Professor, Washington University School of Medicine, Departments of Microbiology & Immunology and of Genetics |
| 1981-1983 | Associate Professor, Washington University School of Medicine, Departments of Microbiology & Immunology and of Genetics |
| 1984-1990 | Professor, Washington University School of Medicine, Departments of Microbiology & Immunology and of Genetics |
| 1990-Present | Alumni Endowed Professor of Molecular Microbiology Washington University School of Medicine |
| 2004-Present | Professor, Department of Medicine Washington University School of Medicine |
Editorial service | |
| 1985-1990 | Associate Editor, Genetics |
| Jan. 1991-1993 | Associate Editor, Plasmid |
| Jan. 1992-present | Editorial Board, Journal of Bacteriology |
| Jan. 1995-present | Journal of Clinical Microbiology |
Honors | |
| Honorary Doctor of Medicine, University of Umeå, Sweden | |
| Membership in American Academy of Microbiology | |
Return to Molecular Microbiology Home Page | |
| Send suggestions and comments to: www@borcim.wustl.edu
WWW | |
| Tel 314-362-7250, FAX 314-362-1232 | |