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Pharmaceuticals 2016, 9(3), 56; doi:10.3390/ph9030056

Therapeutic Potential of Gramicidin S in the Treatment of Root Canal Infections

1
Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, Karlsruhe 76131, Germany
2
Institute of Biological Interfaces (IBG-2), KIT, P. O. Box 3640, Karlsruhe 76021, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Guangshun Wang
Received: 27 May 2016 / Revised: 17 August 2016 / Accepted: 23 August 2016 / Published: 7 September 2016
(This article belongs to the Special Issue Antimicrobial Peptides: Expanded Activity Spectrum and Applications)
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Abstract

An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired tetracycline resistance. In these cases, root canal infections are commonly treated with Ledermix® paste, which contains demeclocycline, or the new alternative endodontic paste Odontopaste, which contains clindamycin; however, these treatments are often ineffective. We studied the killing activity of the cyclic antimicrobial peptide gramicidin S (GS) against planktonic and biofilm cells of tetracycline-resistant clinical isolates of E. faecalis. The high therapeutic potential of GS for the topical treatment of problematic teeth is based on the rapid bactericidal effect toward the biofilm-forming, tetracycline-resistant E. faecalis. GS reduces the cell number of planktonic cells within 20–40 min at a concentration of 40–80 μg/mL. It kills the cells of pre-grown biofilms at concentrations of 100–200 μg/mL, such that no re-growth is possible. The translocation of the peptide into the cell interior and its complexation with intracellular nucleotides, including the alarmon ppGpp, can explain its anti-biofilm effect. The successful treatment of persistently infected root canals of two volunteers confirms the high effectiveness of GS. The broad GS activity towards resistant, biofilm-forming E. faecalis suggests its applications for approval in root canal medication. View Full-Text
Keywords: gramicidin S; Enterococcus faecalis; tetracycline resistance; biofilms; root canal infections; alarmone ppGpp; polymyxin B gramicidin S; Enterococcus faecalis; tetracycline resistance; biofilms; root canal infections; alarmone ppGpp; polymyxin B
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Berditsch, M.; Lux, H.; Babii, O.; Afonin, S.; Ulrich, A.S. Therapeutic Potential of Gramicidin S in the Treatment of Root Canal Infections. Pharmaceuticals 2016, 9, 56.

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