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Published (Version of record)CC BY V4.0, Open Access
Journal article
Relacin, a Novel Antibacterial Agent Targeting the Stringent Response
PLoS pathogens, Vol.8(9), pp.e1002925-e1002925
20/Sep/2012
PMCID: PMC3447753
PMID: 23028324
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.
Details
- Title
- Relacin, a Novel Antibacterial Agent Targeting the Stringent Response
- Creators
- Ezequiel Wexselblatt - Hebrew Univ Jerusalem, Sch Pharm, Inst Drug Res, IL-91120 Jerusalem, IsraelYaara Oppenheimer-Shaanan - Hebrew University of JerusalemIlana Kaspy - Hebrew University of JerusalemNir London - Hebrew University of JerusalemOra Schueler-Furman - Hebrew University of JerusalemEylon Yavin - Hebrew Univ Jerusalem, Sch Pharm, Inst Drug Res, IL-91120 Jerusalem, IsraelGad Glaser - Hebrew University of JerusalemJoshua Katzhendler - Hebrew University of JerusalemSigal Ben-Yehuda - Hebrew University of Jerusalem
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.8(9), pp.e1002925-e1002925; 20/Sep/2012
- Number of pages
- 10
- Publisher
- Public Library Science
- Language
- English
- DOI
- https://doi.org/10.1371/journal.ppat.1002925
- PMID
- 23028324
- PMCID
- PMC3447753
- Grant note
- This work was supported by the European Research Council (ERC, erc.europa.eu) Starting Grant (209130) awarded to SBY, the Israeli National Academy of Science Foundation (ISF, www.isf.org.il) Grant (374/08) awarded to GG and the German-Israeli Foundation (GIF, www.gif.org.il) Grant (835/2004 and 943-334.9/ 2006) awarded to JK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Three first authors contributed equally to this work. We thank R. Losick (Harvard U), A. Rouvinski (Hebrew U) and B. Traag (Harvard U) for comments on the manuscripts. We are grateful to M. Ravins (Hebrew U), C. Block and R. Nir-Paz (Hadassah Medical Center) for technical help. We thank C. Block (Hadassah Medical Center), M. Cashel (NIH), E. Hanski (Hebrew U) and R. Rudner (Hunter College) for providing strains. We are indebted to members of the Ben-Yehuda laboratory, for valuable help and discussions, especially to A. Rosenberg and E. Segev for contributing strains and G. Mamou for technical help. Relacin is the subject of a provisional application for patent: application No. 61/431,902 01/2011. Author Contributions: Conceived and designed the experiments: EW YOS IK NL OSF EY GG JK SBY. Performed the experiments: EW YOS IK NL OSF. Analyzed the data: EW YOS IK NL OSF EY GG JKSBY. Wrote the paper: EW YOS SBY.
- Record Identifier
- 993403981803596
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