Antimicrobial Discovery Center
The Antimicrobial Discovery Center(ADC) is a molecular microbiology group at Northeastern University studying bacterial persister cells, drug discovery, unculturable microorganisms, and Mycobacterium tuberculosis.ADC in the News
A recent study of uncultured bacteria by Professor Kim Lewis and members of the ADC was featured on the Discover Magazine website, and is one of the top Hidden Jewels on Faculty of 1000.
Director Kim Lewis and the Antimicrobial Discovery Center were recently featured in the Boston Globe for research on Persisters in PloS Biology.
Persister Cells
All bacterial populations stochastically produce a small number of dormant persister cells tolerant to antibiotics. Persisters are not mutants but phenotypic variants of the wild type.We are interested in discovering the mechanism of persister formation. Using cell sorting and transcriptome analysis, we find that chromosomally-encoded "toxin" genes act to shut down cellular functions, creating a dormant state. Examples include HipA, a protein kinase that phosphorylates elongation factor Ef-Tu, blocking protein synthesis, and TisB, a small peptide that inserts in the membrane, causing a...(more)
Mycobacterium tuberculosis
The problem of persisting dormant cells is especially acute in the case of tuberculosis - every third person is a non-symptomatic carrier of a "latent" form. This latent form, which we think are persister cells, then wakes up causing an active disease.With support from The Gates Foundation, we are studying the mechanism of persister formation in M. tuberculosis. The focus is on isolating persisters from in vitro grown cultures and also from infected macrophages and mice and obtaining their transcriptome in search of persister genes. Another approach we are using is to... (more)
Drug Discovery
There are several formidable challenges in antimicrobial drug discovery that make this field intellectually appealing. First, there is an “innovation gap” – no new broad-spectrum class of antibiotics has been discovered in the past 40 years. Moreover no antibiotic has ever been able to completely sterilize an infection due to the presence of persisters cells. (more)
Unculturables
The vast majority of microorganisms on this planet are "uncultured" - only 1% will grow on a Petri dish. Why do most microorganisms refuse to grow on perfectly nutritious media in the lab? This is a profound paradox that we are trying to solve.In collaboration with Slava Epstein from our Biology Department, we developed several methods to grow uncultured microorganisms. The basic idea is to grow the organisms in their natural environment in pure culture. We do this by... (more)
SEM Images of Sand Biofilm