The focus of my research is on antimicrobial drug tolerance and drug discovery.
Microorganisms produce persister cells, which are dormant variants that are highly
tolerant to killing by all known antibiotics. Persisters are largely responsible for
relapsing chronic infections caused by biofilms. Using transcriptome analysis, cell
sorting and whole genome sequencing we are identifying genes responsible for persister
formation. Both drug tolerance and conventional drug resistance require development of
new antibiotics, and our discovery efforts include screening compounds from previously
"uncultured" species of microorganisms, and high-throughput screening for
compounds with novel mode of action. 

Articles

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Regulation of the Escherichia coli HipBA toxin-antitoxin system by proteolysis (with Sonja Hansen, Marin Vulić, Tien-Jui Yen, Maria A. Schumacher, and Richard G. Brennan), Biology Faculty Publications (2012)

Bacterial populations produce antibiotic-tolerant persister cells. A number of recent studies point to the involvement...

 

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Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli (with Tobias Dörr and Marin Vulić), Biology Faculty Publications (2010)

Bacteria induce stress responses that protect the cell from lethal factors such as DNA-damaging agents....

 

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Berberine-INF55 (5-nitro-2-phenylindole) hybrid antimicrobials: effects of varying the relative orientation of the berberine and INF55 components (with Danuta Tomkiewicz, Gabriele Casadei, Jonah Larkins-Ford, Terence I. Moy, James A. Garner, John B. Bremner, Frederik M. Ausubel, and Michael J. Kelso), Antimicrobial Agents and Chemotherapy (2010)

Hybrid antimicrobials containing an antibacterial linked to a multidrug resistance (MDR) pump inhibitor make up...

 

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SOS response induces persistence to fluoroquinolones in Escherichia coli (with Tobias Dörr and Marin Vulić), Biology Faculty Publications (2009)

Bacteria can survive antibiotic treatment without acquiring heritable antibiotic resistance. We investigated persistence to the...

 
Structure-activity relationships of 2-aryl-1H-indole inhibitors of the NorA efflux pump in Staphylococcus aureus (with John B. Bremner, Michael J. Kelso, Joseph Ambrus, Anthony R. Ball, and Gabriele Casadei), Faculty of Science - Papers (2008)

The synthesis of 22 2-aryl-1H-indoles, including 12 new compounds, has been achieved via Pd- or...