Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound

Abstract

In staphylococci, quorum sensing regulates both biofilm formation and toxin production, moreover it has been demonstrated to be inhibited by RNAIII inhibiting peptide (RIP). Aim our study was to evaluate the in vitro activity and its in vivo efficacy of the combined administration of FS10, a novel RIP derivative, and tigecycline in an animal model of methicillin-resistant (MR) and methicillin-sensitive (MS) Staphylococcus aureus wound infection. Using a 1.x2 cm template, one full thickness wound was established through the panniculus carnosus on the back subcutaneous tissue of each animal. Infection was determined by inoculation of 5x107 CFU/ml of bacteria, that produced an abscess within 24 h, after this, treatment was initiated. The study included, for each strain, a control group without infection, a control infected group that did not receive any treatment and a control infected group with drug-free foam dressing, and three infected groups treated, respectively, with: FS10-soaked foam dressing (containing 20 μg FS10), daily intraperitoneal tigecycline (7 mg/Kg), FS10-soaked foam dressing (containing 20 μg FS10) and daily intraperitoneal injections of tigecycline (7 mg/Kg). The main outcome measures were quantitative culture and histological examination of tissue repair. The highest inhibition of infection was achieved in the group that received FS10-soaked and parenteral tigecycline reducing the bacterial load from 107 CFU/ml to about 103 CFU/g for MSSA and to about 104 CFU/g for MRSA. The group treated with FS10-soaked foam dressing associated with parenteral tigecycline showed, histologically, better overall healing with epithelialization and collagen scores significantly higher than those of the other groups in both strains. In conclusion, the combined use of topical FS10 with i.p. tigecycline induced positive interaction in vivo, resulting in an enhanced therapeutic benefit versus staphylococcal infections in murine wound models.

Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?

“…A follow-up report detailed the optimization of mBTL for enhanced stability, as the thiolactone ring is susceptible to chemical and enzymatic hydrolysis (110). Other anti-quorum-sensing agents (111)(112)(113)(114) have also been reported to exhibit similar promising in vitro and in vivo results. However, this paradigm was recently challenged (115,116), and several clinical isolates have been reported to be resistant to established anti-quorum-sensing agents (117).…”

Antivirulence properties and related mechanisms of spice essential oils: A comprehensive review

“…Overall, spice essential oils can mainly block the QS system by inhibiting the synthesis of QS signaling molecules and inactivating QS signal receptors. However, the analogs of signal molecule AIP are mainly obtained through chemical synthesis or microbial metabolites, and QSIs derived from spice essential oils are limited (Daly et al., 2015; Simonetti et al., 2016). Therefore, it is of great significance to discover novel hyperactive and safe QSIs from spice essential oils or other plant sources.…”

Novel hamamelitannin analogues for the treatment of biofilm related MRSA infections–A scaffold hopping approach

“…[18] Interestingly, this reaction also yielded a heterocyclic spiro compound (16) in which the Boc-protected amine and the tertiary alcohol are connected via a methylene group to form an oxazolidine ring. Although 1 H NMR and HRMS confirmed the structure of 16, further structural proof was given by 13 C NMR and a 2D 13 C-1 H HSQC experiment, in which a cross peak was observed between the protons at the hemiaminal carbon and their proximate 13 C (Supporting information). Removal of the acetate in 15 under standard conditions gave alcohol 17.…”