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.