Dr. Hoffman research program focuses on molecular mechanisms of microbial pathogenesis by enteric bacterial pathogens and parasites.
Legionella pneumophila is an intracellular parasite of fresh water amoeba that when transmitted by aerosol to humans often causes severe pneumonia.
Legionella is a model system for the study of obligate intracellular pathogens such as
Chlamydia and
Coxiella.
Helicobacter pylori colonizes the gastric mucosa of humans, a niche that is hostile to other microbes. We are studying the mechanisms of long-term persistence in the host and its dual role as a pathogen versus and commensal organism. Dr. Hoffman laboratory has been involved in the study of drug resistance and in the development of new genomic and bioinformatic based strategies for identifying new microbial targets to aid the discovery of new therapeutics. We have synthesized a novel antibiotic Amixicile that is a potent inhibitor of pyruvate ferredoxin oxidoreductase and related alpha keto acid decarboxylases common to all strictly anaerobic bacteria, anaerobic human parasites and to microaerobic human pathogens
Helicobacter pylori and
Campylobacter jejuni. Dr. Hoffman discovered the basis for metronidazole resistance in H. pylori. The target is not found in humans or probiotic beneficial microorganisms. Amixicle shows efficacy against
Clostridium difficile and
H. pylori in mouse infection models. Related analogues with different chemistries show efficacy against biofilm producing bacteria and against
Legionella pneumophila,
Bacillus anthracis and MRSA strains of
Staphylococcus aureus. He serves on the editorial board of several microbiology journals, including the Journal of Bacteriology and serves as a standing member of the VA Infectious Disease study section. Additionally, Dr. Hoffman led an anti-infectives research program as Assistant Director of the Anti-infectives Research Division at GlaxoSmithKline and was a Professor of Infectious Diseases at University of Virginia.
