Relacin, a Novel Antibacterial Agent Targeting the Stringent Response

Ezequiel Wexselblatt, Yaara Oppenheimer-Shaanan, Ilana Kaspy, Nir London, Ora Schueler-Furman, Eylon Yavin, Gad Glaser, Joshua Katzhendler, Sigal Ben-Yehuda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

Finding bacterial cellular targets for developing novel antibiotics has become a major challenge in fighting resistant pathogenic bacteria. We present a novel compound, Relacin, designed to inhibit (p)ppGpp production by the ubiquitous bacterial enzyme RelA that triggers the Stringent Response. Relacin inhibits RelA in vitro and reduces (p)ppGpp production in vivo. Moreover, Relacin affects entry into stationary phase in Gram positive bacteria, leading to a dramatic reduction in cell viability. When Relacin is added to sporulating Bacillus subtilis cells, it strongly perturbs spore formation regardless of the time of addition. Spore formation is also impeded in the pathogenic bacterium Bacillus anthracis that causes the acute anthrax disease. Finally, the formation of multicellular biofilms is markedly disrupted by Relacin. Thus, we establish that Relacin, a novel ppGpp analogue, interferes with bacterial long term survival strategies, placing it as an attractive new antibacterial agent.

Original languageAmerican English
Article numbere1002925
JournalPLoS Pathogens
Volume8
Issue number9
DOIs
StatePublished - Sep 2012

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