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bioRxiv · 10.1101/737320

Therapeutically Exploring Persister Metabolism In Bacteria

Orman, M.·Mohiuddin, S. G.·Karki, P.·Saba, A.·Hoang, T.
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Abstract

Bacterial persisters are rare phenotypic variants that are temporarily tolerant to high concentrations of antibiotics. We have previously discovered that persisters are mostly derived from stationary-phase cells with high redox activities that are maintained by endogenous protein and RNA degradation. This intracellular degradation resulted in self-inflicted damage that transiently repressed the cellular functions targeted by antibiotics. Leveraging this knowledge, we developed an assay integrating a degradable fluorescent protein system and a small library, containing FDA-approved drugs and antibiotics, to detect chemicals that target persister metabolism. We identified several metabolic inhibitors, including anti-psychotic drugs, that can reduce Escherichia coli persistence. These chemical inhibitors also reduce Pseudomonas aeruginosa persistence, potentially verifying the existence of similar mechanisms in a medically relevant organism.

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Orman, M., Mohiuddin, S. G., Karki, P., Saba, A., Hoang, T.. 2019-08-15. Therapeutically Exploring Persister Metabolism In Bacteria. https://doi.org/10.1101/737320

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