Preliminary results of a novel quorum sensing inhibitor against pneumococcal infection and biofilm formation with special interest to otitis media and cochlear implantation

Abstract

The purpose of the study is to assess the effect of a novel quorum sensing inhibitor (QSI), coded as 'yd 47', against otitis media and biofilm formation on Cochlear implants (CIs). Small pieces cut from cochlear implant were implanted under the skin in the retroauricular area on both sides of four guinea pigs. The implant pieces in the study and control sides were implanted in Streptococcus pneumoniae strain solution and saline, respectively. The right and left middle ears were also instilled with a solution containing pneumococci and saline, respectively. The animals were only given an intraperitoneal 'yd 47' twice daily for three months to be assessed later with electron microscopy. Clinical examination with palpation, inspection and otoscopy did not reveal any sign of implant infection or otitis media. In the study and control implant materials, soft tissues around the implant and tympanic membranes, there was no biofilm formation by pneumococci. Contamination by various cells and some rod-shaped bacteria (not diplococcic) were seen in some of the materials. In conclusion, the novel QSI seems promising in the prevention of otitis media and biofilm formation on CIs by pneumococci.

Antimicrobial Photodynamic Therapy to Control Clinically Relevant Biofilm Infections

“…Some plant-derived natural products can interfere with QS, that might explain their use to treat microbial infections, such as Quercus infectoria Olivier (Chusri et al, 2012 ), Curcuma longa L. (Packiavathy et al, 2014 ), Allium sativum L. (Bjarnsholt et al, 2005 ), essential oils from Cinnamomum verum Pres (Niu et al, 2006 ), and Syzygium aromaticum (L.) Merrill & Perry (Khan et al, 2009 ), and methanol extract of Kalanchoe blossfeldiana (Sarkar et al, 2015 ). Other compounds targeting QS such as synthetic furanones (Wu et al, 2004 ), the fatty acid messenger cis -2-decenoic acid (Davies and Marques, 2009 ), and QS inhibitor “yd 47” have all displayed some efficacy against biofilms (Cevizci et al, 2015 ). Some proteins and peptides can also suppress biofilm by interfering with QS, such as RNA-III-inhibiting peptide (RIP) (Balaban et al, 2007 ), a competence-stimulating peptide (LoVetri and Madhyastha, 2010 ), and an analog of competence stimulating peptide (KBI-3221).…”

In vitro and in vivo Evaluation of in silico Predicted Pneumococcal UDPG:PP Inhibitors

“…However, their mechanism of action might also include inhibition of autolysin ( Jindal et al, 2015 , 2017 ). Finally, quorum sensing inhibitors have proven to effectively prevent in vitro and/or in vivo biofilm formation on middle ear implants and migration of pneumococci to the blood ( Yadav et al, 2012 , 2014 , 2015 ; Cevizci et al, 2015 ; Motib et al, 2017 ).…”

Pathway-Centric Structure-Based Multi-Target Compound Screening for Anti-Virulence Drug Repurposing

“…Thus, the clinical use of azithromycin in controlling drug-resistant infections of P. aeruginosa is uncertain. Several active compounds have been discovered which reduce the virulence of P. aeruginosa by inhibiting quorum-sensing that regulates the production of pyocyanin virulence factors, through experimental compound screenings [18,19,20,21,22,23,24,25,26,27]. However, few of these compounds are in the preclinical or clinical stage.…”