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

Cevizci, Raşit; Düzlü, Mehmet; Dündar, Yasemin; Noyanalpan, Ningur; Sultan, Nedim; Tutar, Hakan; Bayazıt, Yıldırım A.

doi:10.1007/s00405-014-2942-5

Cited by 16 publications

(12 citation statements)

References 15 publications

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“…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).…”

Section: Investigative Control Strategies For Biofilmsmentioning

confidence: 99%

Antimicrobial Photodynamic Therapy to Control Clinically Relevant Biofilm Infections

et al. 2018

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Biofilm describes a microbially-derived sessile community in which microbial cells are firmly attached to the substratum and embedded in extracellular polymeric matrix. Microbial biofilms account for up to 80% of all bacterial and fungal infections in humans. Biofilm-associated pathogens are particularly resistant to antibiotic treatment, and thus novel antibiofilm approaches needed to be developed. Antimicrobial Photodynamic therapy (aPDT) had been recently proposed to combat clinically relevant biofilms such as dental biofilms, ventilator associated pneumonia, chronic wound infections, oral candidiasis, and chronic rhinosinusitis. aPDT uses non-toxic dyes called photosensitizers (PS), which can be excited by harmless visible light to produce reactive oxygen species (ROS). aPDT is a multi-stage process including topical PS administration, light irradiation, and interaction of the excited state with ambient oxygen. Numerous in vitro and in vivo aPDT studies have demonstrated biofilm-eradication or substantial reduction. ROS are produced upon photo-activation and attack adjacent targets, including proteins, lipids, and nucleic acids present within the biofilm matrix, on the cell surface and inside the microbial cells. Damage to non-specific targets leads to the destruction of both planktonic cells and biofilms. The review aims to summarize the progress of aPDT in destroying biofilms and the mechanisms mediated by ROS. Finally, a brief section provides suggestions for future research.

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Section: Investigative Control Strategies For Biofilmsmentioning

confidence: 99%

Antimicrobial Photodynamic Therapy to Control Clinically Relevant Biofilm Infections

et al. 2018

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“…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 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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Pneumonia, of which Streptococcus pneumoniae is the most common causative agent, is considered one of the three top leading causes of death worldwide. As seen in other bacterial species, antimicrobial resistance is on the rise for this pathogen. Therefore, there is a pressing need for novel antimicrobial strategies to combat these infections. Recently, uridine diphosphate glucose pyrophosphorylase (UDPG:PP) has been put forward as a potential drug target worth investigating. Moreover, earlier research demonstrated that streptococci lacking a functional galU gene (encoding for UDPG:PP) were characterized by significantly reduced in vitro and in vivo virulence. Therefore, in this study we evaluated the anti-virulence activity of potential UDPG:PP inhibitors. They were selected in silico using a tailor-made streptococcal homology model, based on earlier listerial research. While the compounds didn't affect bacterial growth, nor affected in vitro adhesion to and phagocytosis in macrophages, the amount of polysaccharide capsule was significantly reduced after co-incubation with these inhibitors. Moreover, co-incubation proved to have a positive effect on survival in an in vivo Galleria mellonella larval infection model. Therefore, rather than targeting bacterial survival directly, these compounds proved to have an effect on streptococcal virulence by lowering the amount of polysaccharide and thereby probably boosting recognition of this pathogen by the innate immune system. While the compounds need adaptation to broaden their activity to more streptococcal strains rather than being strain-specific, this study consolidates UDPG:PP as a potential novel drug target.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Xie

2019

IJMS

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The emergence of superbugs that are resistant to last-resort antibiotics poses a serious threat to human health, and we are in a “race against time to develop new antibiotics.” New approaches are urgently needed to control drug-resistant pathogens, and to reduce the emergence of new drug-resistant microbes. Targeting bacterial virulence has emerged as an important strategy for combating drug-resistant pathogens. It has been shown that pyocyanin, which is produced by the phenazine biosynthesis pathway, plays a key role in the virulence of Pseudomonas aeruginosa infection, making it an attractive target for anti-infective drug discovery. In order to discover efficient therapeutics that inhibit the phenazine biosynthesis in a timely fashion, we screen 2004 clinical and pre-clinical drugs to target multiple enzymes in the phenazine biosynthesis pathway, using a novel procedure of protein–ligand docking. Our detailed analysis suggests that kinase inhibitors, notably Lifirafenib, are promising lead compounds for inhibiting aroQ, phzG, and phzS enzymes that are involved in the phenazine biosynthesis, and merit further experimental validations. In principle, inhibiting multiple targets in a pathway will be more effective and have less chance of the emergence of drug resistance than targeting a single protein. Our multi-target structure-based drug design strategy can be applied to other pathways, as well as provide a systematic approach to polypharmacological drug repositioning.

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

Cited by 16 publications

References 15 publications

Antimicrobial Photodynamic Therapy to Control Clinically Relevant Biofilm Infections

Antimicrobial Photodynamic Therapy to Control Clinically Relevant Biofilm Infections

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

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

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