Dr. Lewis has authored over 100 papers and is an inventor on several patents. His notable findings include the development of general methods to grow previously uncultured bacteria that make up >99% of biodiversity on the planet, the discovery of the culprit of recalcitrant biofilm infections, drug-tolerant persister cells; and several novel antibiotics.
Dr. Lewis has been a permanent member of the Drug Discovery and Drug Resistance NIH Study Section, and Chair of two NIH Study Sections on Drug Discovery. Dr. Lewis has served as a panelist and contributor to reports on antimicrobial resistance (AMR) by National Academies Institute of Medicine, the Pew Charitable Trust, and the European Academies of Science. Dr. Lewis is a member of Faculty 1000, a world-wide panel of experts evaluating research advancements. He is a recipient of the MIT C.E. Reed Faculty Initiative Award and is a recipient of the NIH Director’s Transformative Award.
Interesting Compounds from Microbiome Mining
Environmental microbiomes are characterized by the dominance of “uncultured” bacteria that do not readily grow in vitro. We have been developing general methods to access uncultured bacteria – growth in situ and identification of growth factors such as siderophores. From previously uncultured bacteria, we discovered several novel antimicrobials, including teixobactin, the first antibiotic without detectable resistance. The animal microbiome is an untapped source of interesting chemistry. We identified growth factors for uncultured bacteria of the human microbiome, including, surprisingly, GABA. The nematode microbiome produced several compounds with unusual mode of action. Discovering novel compounds acting against Gram-negative bacteria is especially challenging. From the nematode symbionts Photorhabdus we isolated darobactins that bind the “non-druggable” protein BamA on the surface of the outer membrane, and ADG, a prodrug mimic of GTP acting against Enterobacteriaceae. The microbiomes still remain a largely unexplored source of natural products.