scholarly journals Phytochemical Composition and In Vitro Biological Activity of Iris spp. (Iridaceae): A New Source of Bioactive Constituents for the Inhibition of Oral Bacterial Biofilms

Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 403 ◽  
Author(s):  
Lan Hoang ◽  
František Beneš ◽  
Marie Fenclová ◽  
Olga Kronusová ◽  
Viviana Švarcová ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
High Performance ◽  
Human Fibroblasts ◽  
Antibiofilm Activity ◽  
Dependent Manner ◽  
Bioactive Constituents ◽  
Concentration Dependent Manner ◽  
Oral Biofilms

The inhibition and eradication of oral biofilms is increasingly focused on the use of plant extracts as mouthwashes and toothpastes adjuvants. Here, we report on the chemical composition and the antibiofilm activity of 15 methanolic extracts of Iris species against both mono-(Pseudomonas aeruginosa, Staphylococcus aureus) and multi-species oral biofilms (Streptococcus gordonii, Veillonella parvula, Fusobacterium nucleatum subsp. nucleatum, and Actinomyces naeslundii). The phytochemical profiles of Iris pallida s.l., Iris versicolor L., Iris lactea Pall., Iris carthaliniae Fomin, and Iris germanica were determined by ultra-high performance liquid chromatography-high-resolution tandem mass spectroscopy (UHPLC-HRMS/MS) analysis, and a total of 180 compounds were identified among Iris species with (iso)flavonoid dominancy. I. pallida, I. versicolor, and I. germanica inhibited both the quorum sensing and adhesion during biofilm formation in a concentration-dependent manner. However, the extracts were less active against maturated biofilms. Of the five tested species, Iris pallida s.l. was the most effective at both inhibiting biofilm formation and disrupting existing biofilms, and the leaf extract exhibited the strongest inhibitory effect compared to the root and rhizome extracts. The cytotoxicity of the extracts was excluded in human fibroblasts. The inhibition of bacterial adhesion significantly correlated with myristic acid content, and quorum sensing inhibition correlated with the 7-β-hydroxystigmast-4-en-3-one content. These findings could be useful for establishing an effective tool for the control of oral biofilms and thus dental diseases.

An Alanine-Rich Peptide Attenuates Quorum Sensing-Regulated Virulence and Biofilm Formation in Staphylococcus aureus

2019 ◽  
Vol 102 (4) ◽  
pp. 1228-1234 ◽  
Author(s):  
Raid Al Akeel ◽  
Ayesha Mateen ◽  
Rabbani Syed
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Bacterial Attachment ◽  
The Body ◽  
Dependent Manner ◽  
Virulence Determinants ◽  
Microarray Gene Expression ◽  
Concentration Dependent Manner

Abstract Background: Alanine-rich proteins/peptides (ARP), with bioactivity of up to 20 amino acid residues, can be observed by the body easily during gastrointestinal digestion. Objective: Populus trichocarpa extract’s capability to attenuate quorum sensing-regulated virulence and biofilm formation in Staphylococcus aureus is described. Methods: PT13, an ARP obtained from P. trichocarpa, was tested for its activity against S. aureus using the broth microdilution test; a crystal-violet biofilm assay was performed under a scanning electron microscope. The production of various virulence factors was estimated with PT13 treatment. Microarray gene expression profiling of PT13-treated S. aureus was conducted and compared with an untreated control. Exopolysaccharides (EPS) was estimated to observe the PT13 inhibition activity. Results: PT13 was antimicrobial toward S. aureus at different concentrations and showed a similar growth rate in the presence and absence of PT13 at concentrations ≤8 μg/mL. Biofilm production was interrupted even at low concentrations, and biofilm-related genes were down-regulated when exposed to PT13. The genes encoding cell adhesion and bacterial attachment protein were the major genes suppressed by PT13. In addition, hemolysins, clumping activity, and EPS production of S. aureus decreased after treatment in a concentration-dependent manner. Conclusions: A long-chain PT13 with effective actions that, even at low concentration levels, not only regulated the gene expression in the producer organism but also blocked the virulence gene expression in this Gram-positive human pathogen is described. Highlights: We identified a PT13 as a potential antivirulence agent that regulated production of bacterial virulence determinants (e.g., toxins, enzymes and biofilm), downwards and it may be a promising anti-virulence agent to be further developed as an anti-infective agent.

scholarly journals Peptide Mix from Olivancillaria hiatula Interferes with Cell-to-Cell Communication in Pseudomonas aeruginosa

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Edward Ntim Gasu ◽  
Hubert Senanu Ahor ◽  
Lawrence Sheringham Borquaye
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Cell Communication ◽  
Microtiter Plate ◽  
Antibiofilm Activity ◽  
Dependent Manner ◽  
Biofilm Inhibition ◽  
Swarming Motility

Bacteria in biofilms are encased in an extracellular polymeric matrix that limits exposure of microbial cells to lethal doses of antimicrobial agents, leading to resistance. In Pseudomonas aeruginosa, biofilm formation is regulated by cell-to-cell communication, called quorum sensing. Quorum sensing facilitates a variety of bacterial physiological functions such as swarming motility and protease, pyoverdine, and pyocyanin productions. Peptide mix from the marine mollusc, Olivancillaria hiatula, has been studied for its antibiofilm activity against Pseudomonas aeruginosa. Microscopy and microtiter plate-based assays were used to evaluate biofilm inhibitory activities. Effect of the peptide mix on quorum sensing-mediated processes was also evaluated. Peptide mix proved to be a good antibiofilm agent, requiring less than 39 μg/mL to inhibit 50% biofilm formation. Micrographs obtained confirmed biofilm inhibition at 1/2 MIC whereas 2.5 mg/mL was required to degrade preformed biofilm. There was a marked attenuation in quorum sensing-mediated phenotypes as well. At 1/2 MIC of peptide, the expression of pyocyanin, pyoverdine, and protease was inhibited by 60%, 72%, and 54%, respectively. Additionally, swarming motility was repressed by peptide in a dose-dependent manner. These results suggest that the peptide mix from Olivancillaria hiatula probably inhibits biofilm formation by interfering with cell-to-cell communication in Pseudomonas aeruginosa.

scholarly journals PYED-1 Inhibits Biofilm Formation and Disrupts the Preformed Biofilm of Staphylococcus aureus

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 240 ◽  
Author(s):  
Adriana Vollaro ◽  
Anna Esposito ◽  
Eliana Pia Esposito ◽  
Raffaele Zarrilli ◽  
Annalisa Guaragna ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Surface Proteins ◽  
Transcriptional Analysis ◽  
Capsular Polysaccharides ◽  
Dependent Manner ◽  
Chronic Infections ◽  
Concentration Dependent Manner ◽  
Expression Of Genes

Pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1 (PYED-1), a heterocyclic corticosteroid derivative of deflazacort, exhibits broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacteria. Here, we investigated the effect of PYED-1 on the biofilms of Staphylococcus aureus, an etiological agent of biofilm-based chronic infections such as osteomyelitis, indwelling medical device infections, periodontitis, chronic wound infections, and endocarditis. PYED-1 caused a strong reduction in biofilm formation in a concentration dependent manner. Furthermore, it was also able to completely remove the preformed biofilm. Transcriptional analysis performed on the established biofilm revealed that PYED-1 downregulates the expression of genes related to quorum sensing (agrA, RNAIII, hld, psm, and sarA), surface proteins (clfB and fnbB), secreted toxins (hla, hlb, and lukD), and capsular polysaccharides (capC). The expression of genes that encode two main global regulators, sigB and saeR, was also significantly inhibited after treatment with PYED-1. In conclusion, PYED-1 not only effectively inhibited biofilm formation, but also eradicated preformed biofilms of S. aureus, modulating the expression of genes related to quorum sensing, surface and secreted proteins, and capsular polysaccharides. These results indicated that PYED-1 may have great potential as an effective antibiofilm agent to prevent S. aureus biofilm-associated infections.

scholarly journals Interaction of Rifampin and Darunavir-Ritonavir or Darunavir-Cobicistat In Vitro

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Owain Roberts ◽  
Saye Khoo ◽  
Andrew Owen ◽  
Marco Siccardi
Keyword(s):  
High Performance ◽  
Linear Regression Analysis ◽  
Intrinsic Clearance ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Content Type ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Dosing Regimens

ABSTRACT Treatment of HIV-infected patients coinfected with Mycobacterium tuberculosis is challenging due to drug-drug interactions (DDIs) between antiretrovirals (ARVs) and antituberculosis (anti-TB) drugs. The aim of this study was to quantify the effect of cobicistat (COBI) or ritonavir (RTV) in modulating DDIs between darunavir (DRV) and rifampin (RIF) in a human hepatocyte-based in vitro model. Human primary hepatocyte cultures were incubated with RIF alone or in combination with either COBI or RTV for 3 days, followed by coincubation with DRV for 1 h. The resultant DRV concentrations were quantified by high-performance liquid chromatography with UV detection, and the apparent intrinsic clearance (CLint.app.) of DRV was calculated. Both RTV and COBI lowered the RIF-induced increases in CLint.app. in a concentration-dependent manner. Linear regression analysis showed that log10 RTV and log10 COBI concentrations were associated with the percent inhibition of RIF-induced elevations in DRV CLint.app., where β was equal to −234 (95% confidence interval [CI] = −275 to −193; P < 0.0001) and −73 (95% CI = −89 to −57; P < 0.0001), respectively. RTV was more effective in lowering 10 μM RIF-induced elevations in DRV CLint.app. (half-maximal [50%] inhibitory concentration [IC50] = 0.025 μM) than COBI (IC50 = 0.223 μM). Incubation of either RTV or COBI in combination with RIF was sufficient to overcome RIF-induced elevations in DRV CLint.app., with RTV being more potent than COBI. These data provide the first in vitro experimental insight into DDIs between RIF and COBI-boosted or RTV-boosted DRV and will be useful to inform physiologically based pharmacokinetic (PBPK) models to aid in optimizing dosing regimens for the treatment of patients coinfected with HIV and M. tuberculosis.

scholarly journals Structural Characterization and Antioxidative Activity of Low-Molecular-Weights Beta-1,3-Glucan from the Residue of ExtractedGanoderma lucidumFruiting Bodies

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Pai-Feng Kao ◽  
Shwu-Huey Wang ◽  
Wei-Ting Hung ◽  
Yu-Han Liao ◽  
Chun-Mao Lin ◽  
...  
Keyword(s):  
Cell Death ◽  
High Performance ◽  
Anion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Water Soluble ◽  
Dependent Manner ◽  
Ros Production ◽  
Fruiting Bodies ◽  
Concentration Dependent Manner

The major cell wall constituent ofGanoderma lucidum(G. lucidum) isβ-1,3-glucan. This study examined the polysaccharide from the residues of alkaline-extracted fruiting bodies using high-performance anion-exchange chromatography (HPAEC), and it employed nuclear magnetic resonance (NMR) and mass spectrometry (MS) to confirm the structures. We have successfully isolated low-molecular-weightβ-1,3-glucan (LMG), in high yields, from the waste residue of extracted fruiting bodies ofG. lucidum. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay evaluated the capability of LMG to suppress H2O2-induced cell death in RAW264.7 cells, identifying that LMG protected cells from H2O2-induced damage. LMG treatment decreased H2O2-induced intracellular reactive oxygen species (ROS) production. LMG also influenced sphingomyelinase (SMase) activity, stimulated by cell death to induce ceramide formation, and then increase cell ROS production. Estimation of the activities of neutral and acid SMasesin vitroshowed that LMG suppressed the activities of both neutral and acid SMases in a concentration-dependent manner. These results suggest that LMG, a water-solubleβ-1,3-glucan recycled from extracted residue ofG. lucidum, possesses antioxidant capability against H2O2-induced cell death by attenuating intracellular ROS and inhibiting SMase activity.

scholarly journals Tea polyphenols as an antivirulence compound Disrupt Quorum-Sensing Regulated Pathogenicity of Pseudomonas aeruginosa

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Hongping Yin ◽  
Yifeng Deng ◽  
Huafu Wang ◽  
Wugao Liu ◽  
Xiyi Zhuang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Water Extract ◽  
Tea Polyphenols ◽  
Infection Model ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Treatment Groups

Abstract Green tea, a water extract of non-fermented leaves of Camellia sinensis L., is one of the nonalcoholic beverages in China. It is becoming increasingly popular worldwide, because of its refreshing, mild stimulant and medicinal properties. Here we examined the quorum sensing inhibitory potentials of tea polyphenols (TP) as antivirulence compounds both in vitro and in vivo. Biosensor assay data suggested minimum inhibitory concentrations (MICs) of TP against selected pathogens were 6.25 ~ 12.5 mg/mL. At sub-MIC, TP can specifically inhibit the production of violacein in Chromobacterium violaceum 12472 with almost 98% reduction at 3.125 mg/mL without affecting its growth rate. Moreover, TP exhibited inhibitory effects on virulence phenotypes regulated by QS in Pseudomonas aeruginosa. The total proteolytic activity, elastase, swarming motility and biofilm formation were reduced in a concentration-dependent manner. In vivo, TP treatment resulted in the reduction of P. aeruginosa pathogenicity in Caenorhabditis elegans. When its concentration was 3.125 mg/mL, the survival rate reached 63.3%. In the excision wound infection model, the wound contraction percentage in treatment groups was relatively increased and the colony-forming units (CFU) in the wound area were significantly decreased. These results suggested that TP could be developed as a novel non-antibiotic QS inhibitor without killing the bacteria but as an antivirulence compound to control bacterial infection.

scholarly journals LuxR Homologue SmcR Is Essential for Vibrio vulnificus Pathogenesis and Biofilm Detachment, and Its Expression is Induced by Host Cells

2013 ◽  
Vol 81 (10) ◽  
pp. 3721-3730 ◽  
Author(s):  
Seung Min Kim ◽  
Jin Hwan Park ◽  
Hyun Sung Lee ◽  
Won Bin Kim ◽  
Jung Min Ryu ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Vibrio Vulnificus ◽  
Cell Communication ◽  
Cellular Level ◽  
Host Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Content Type ◽  
Biofilm Detachment

ABSTRACTQuorum sensing is a cell-to-cell communication system known to control many bacterial processes. In the present study, the functions of quorum sensing in the pathogenesis ofVibrio vulnificus, a food-borne pathogen, were assessed by evaluating the virulence of a mutant deficient in SmcR, a quorum-sensing regulator and homologue of LuxR. When biofilms were used as an inoculum, thesmcRmutant was impaired in virulence and colonization capacity in the infection of mice. The lack of SmcR also resulted in decreased histopathological damage in mouse jejunum tissue. These results indicated that SmcR is essential forV. vulnificuspathogenesis. Moreover, thesmcRmutant exhibited significantly reduced biofilm detachment. Upon exposure to INT-407 host cells, the wild type, but not thesmcRmutant, revealed accelerated biofilm detachment. The INT-407 cells increasedsmcRexpression by activating the expression of LuxS, an autoinducer-2 synthase, indicating that host cells manipulate the cellular level of SmcR through the quorum-sensing signaling ofV. vulnificus. A whole-genome microarray analysis revealed that the genes primarily involved in biofilm detachment and formation are up- and downregulated by SmcR, respectively. Among the SmcR-regulated genes,vvpEencoding an elastolytic protease was the most upregulated, and the purified VvpE appeared to dissolve established biofilms directly in a concentration-dependent mannerin vitro. These results suggest that the host cell-induced SmcR enhances the detachment ofV. vulnificusbiofilms entering the host intestine and thereby may promote the dispersal of the pathogen to new colonization loci, which is crucial for pathogenesis.

scholarly journals In vitro antibiofilm activity of resveratrol against avian pathogenic Escherichia coli

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Xiangchun Ruan ◽  
Xiaoling Deng ◽  
Meiling Tan ◽  
Chengbo Yu ◽  
Meishi Zhang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Biofilm Formation ◽  
Inhibitory Concentration ◽  
Laser Scanning Microscopy ◽  
Antibiofilm Activity ◽  
Dependent Manner ◽  
Swarming Motility ◽  
Semisolid Medium ◽  
Broth Microdilution Method

Abstract Background Avian pathogenic Escherichia coli (APEC) strains cause infectious diseases in poultry. Resveratrol is extracted from Polygonum cuspidatum, Cassia tora Linn and Vitis vinifera, and displays good antimicrobial activity. The present study aimed to investigate the antibiofilm effect of resveratrol on APEC in vitro. The minimum inhibitory concentration (MIC) of resveratrol and the antibiotic florfenicol toward APEC were detected using the broth microdilution method. Then, the effect of resveratrol on swimming and swarming motility was investigated using a semisolid medium culture method. Subsequently, the minimum biofilm inhibitory concentration (MBIC) and the biofilm eradication rate were evaluated using crystal violet staining. Finally, the antibiofilm activity of resveratrol was observed using scanning electron microscopy (SEM). Meanwhile, the effects of florfenicol combined with resveratrol against biofilm formation by APEC were evaluated using optical microscopy (OM) and a confocal laser scanning microscopy (CLSM). Results The MICs of resveratrol and florfenicol toward APEC were 128 μg/mL and 64 μg/mL, respectively. The swimming and swarming motility abilities of APEC were inhibited in a resveratrol dose-dependent manner. Furthermore, resveratrol showed a significant inhibitory activity against APEC biofilm formation at concentrations above 1 μg/mL (p < 0.01). Meanwhile, the inhibitory effect of resveratrol at 32 μg/mL on biofilm formation was observed using SEM. The APEC biofilm was eradicated at 32 μg/mL of resveratrol combined with 64 μg/mL of florfenicol, which was observed using CLSM and OM. Florfenicol had a slight eradication effect of biofilm formation, whereas resveratrol had a strong biofilm eradication effect toward APEC. Conclusion Resveratrol displayed good antibiofilm activity against APEC in vitro, including inhibition of swimming and swarming motility, biofilm formation, and could eradicate the biofilm.

scholarly journals Label-Free Monitoring of Uptake and Toxicity of Endoprosthetic Wear Particles in Human Cell Cultures

2018 ◽  
Vol 19 (11) ◽  
pp. 3486 ◽  
Author(s):  
Anika Jonitz-Heincke ◽  
Jenny Tillmann ◽  
Melanie Ostermann ◽  
Armin Springer ◽  
Rainer Bader ◽  
...  
Keyword(s):  
Cell Viability ◽  
Biological Effects ◽  
Human Fibroblasts ◽  
Dependent Manner ◽  
Wear Particles ◽  
Label Free ◽  
Concentration Dependent Manner ◽  
Cellular Behavior ◽  
Alumina Matrix Composite

The evaluation of the biological effects of endoprosthetic wear particles on cells in vitro relies on a variety of test assays. However, most of these methods are susceptible to particle-induced interferences; therefore, label-free testing approaches emerge as more reliable alternatives. In this study, impedance-based real-time monitoring of cellular viability and metabolic activity were performed following exposure to metallic and ceramic wear particles. Moreover, label-free imaging of particle-exposed cells was done by high-resolution darkfield microscopy (HR-ODM) and field emission scanning electron microscopy (FESEM). The isolated human fibroblasts were exposed to CoCr28Mo6 and alumina matrix composite (AMC) ceramic particles. HR-ODM and FESEM revealed ingested particles. For impedance measurements, cells were seeded on gold-plated microelectrodes. Cellular behavior was monitored over a period of 48 h. CoCr28Mo6 and AMC particle exposure affected cell viability in a concentration-dependent manner, i.e., 0.01 mg/mL particle solutions led to small changes in cell viability, while 0.05 mg/mL resulted in a significant reduction of viability. The effects were more pronounced after exposure to CoCr28Mo6 particles. The results were in line with light and darkfield microcopy observations indicating that the chosen methods are valuable tools to assess cytotoxicity and cellular behavior following exposure to endoprosthetic wear particles.

scholarly journals Inhibition of Cytomegalovirus Replication with Extended-Half-Life Synthetic Ozonides

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Yiping Wang ◽  
Rupkatha Mukhopadhyay ◽  
Sujayita Roy ◽  
Arun Kapoor ◽  
Yu-Pin Su ◽  
...  
Keyword(s):  
Half Life ◽  
Cell Cycle Progression ◽  
Early Stage ◽  
Human Fibroblasts ◽  
Dependent Manner ◽  
Therapeutic Success ◽  
Concentration Dependent Manner ◽  
Malaria Therapy

ABSTRACTArtesunate (AS), a semisynthetic artemisinin approved for malaria therapy, inhibits human cytomegalovirus (HCMV) replicationin vitro, but therapeutic success in humans has been variable. We hypothesized that the shortin vivohalf-life of AS may contribute to the different treatment outcomes. We tested novel synthetic ozonides with longer half-lives against HCMVin vitroand mouse cytomegalovirus (MCMV)in vivo. Screening of the activities of four ozonides against a pp28-luciferase-expressing HCMV Towne recombinant identified OZ418 to have the best selectivity; its effective concentration inhibiting viral growth by 50% (EC50) was 9.8 ± 0.2 µM, and cytotoxicity in noninfected human fibroblasts (the concentration inhibiting cell growth by 50% [CC50]) was 128.1 ± 8.0 µM. In plaque reduction assays, OZ418 inhibited HCMV TB40 in a concentration-dependent manner as well as a ganciclovir (GCV)-resistant HCMV isolate. The combination of OZ418 and GCV was synergistic in HCMV inhibitionin vitro. Virus inhibition by OZ418 occurred at an early stage and was dependent on the cell density at the time of infection. OZ418 treatment reversed HCMV-mediated cell cycle progression and correlated with the reduction of HCMV-induced expression of pRb, E2F1, and cyclin-dependent kinases 1, 2, 4, and 6. In an MCMV model, once-daily oral administration of OZ418 had significantly improved efficacy against MCMV compared to that of twice-daily oral AS. A parallel pharmacokinetic study with a single oral dose of OZ418 or AS showed a prolonged plasma half-life and higher unbound concentrations of OZ418 than unbound concentrations of AS. In summary, ozonides are proposed to be potential therapeutics, alone or in combination with GCV, for HCMV infection in humans.

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