Figure 1. Oxyclozanide enhances aminoglycosides and tetracycline

Slides:

Advertisements

Similar presentations

To enhance students ability to interpret data in charts and graphs To discuss basic concepts in epidemiology and science.

Advertisements

In Vitro Discriminative Antipseudomonal Properties Resulting from Acyl Substitution of N-Terminal Sequence of Dermaseptin S4 Derivatives Keren Marynka,

Fig. 1. APG increased the sensitivity of BEL-7402/ADM cells to ADM

From: Disruption of Contact Lens–Associated Pseudomonas aeruginosa Biofilms Formed in the Presence of Neutrophils Invest. Ophthalmol. Vis. Sci ;52(5):

Figure 3. Time–kill curves of exponential phase P

Fig. 4. Effect of FTY720 on brain tumor stem cell (BTSC) invasiveness

Figure 6. RRs for clinical cure rates stratified by different diseases

Figure 1 Annual number of isolates of imipenem-resistant P. aeruginosa

Fluid Phase Endocytosis Contributes to Transfection of DNA by PEI-25

Figure 1. Artemisinin derivatives inhibited EOC growth and arrested the cell cycle at the G2/M phase (A) SKOV3 and primary epithelial ovarian cancer (EOC)

D-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models Daniel J. Fox, Morris D. Cooper, Cristian A.

Rasmus D. Jahnsen, Evan F. Haney, Henrik Franzyk, Robert E.W. Hancock

Effect of glucosamine and its peptidyl-derivative on the production of extracellular matrix components by human primary chondrocytes D. Stoppoloni, L.

Figure 1. HR (95% CI) of death from dementia associated with weight or BMI in middle age and in old age. From: Adiposity in middle and old age and risk.

Figure 4. Influence of Clerk Ideology on Justice Voting.

Involvement of Oxidative Stress in Apoptosis Induced by a Mixture of Isothiazolinones in Normal Human Keratinocytes Anna Ettorre, Paolo Neri, Anna Di.

Biofilm Inhibitors that Target Amyloid Proteins

Figure 1. Ten chemotherapeutic drugs induce the bacterial SOS response

Figure 1. Distribution of ABCB1 SNVs and haplotypes.

Rasmus D. Jahnsen, Evan F. Haney, Henrik Franzyk, Robert E.W. Hancock

Volume 15, Issue 6, Pages (June 2012)

Figure 1. Colistin MIC distribution for the 153 colistin-resistant E

Figure 1. Variation in population size of the donor strain HN-1 and E

Figure 1. Linkage analyses of the SNPs in the MRE11 gene and haplotype blocks. Haplotype blocks were defined for all ... Figure 1. Linkage analyses of.

Figure 1. Structure of two poxtA-carrying plasmids in E

Figure 1 The Kaplan–Meier curves of time to death post first hospitalization. hosp, hospitalization. Unless provided in the caption above, the following.

Figure 1. Serum ceftazidime concentrations following intravenous administration. Unless provided in the caption above, the following copyright applies.

Figure 1. SpeI-PFGE dendrogram comparing P

(A) OA patients with ... (A) OA patients with crystals exhibit an increase in FA levels in SF compared with OA patients without crystals. (B) Patients.

(A) The 10 most commonly involved organs in female and male ...

Figure 1. Uptake of relebactam into human OAT1, OAT3 and OCT2 stably transfected cells. Time-dependent uptake of ... Figure 1. Uptake of relebactam into.

Fig. 1 Flow chart of included patients for analyses

Rats were treated for 21 days ...

Figure 1. Mean log10 cfu/mL versus time profile for each individual drug at 4× MIC against the four VRE ... Figure 1. Mean log10 cfu/mL versus.

Fig. 1 Flow chart for selection of study subjects

Figure 1. Susceptibility of all P

Figure 1. (a) Geographical representation of sample collection area

Adenosine Receptors as Mediators of Both Cell Proliferation and Cell Death of Cultured Human Melanoma Cells Stefania Merighi, Prisco Mirandola, Daniela.

(A–D) Distribution of age (A), mRSS (B), ...

Unless provided in the caption above, the following copyright applies to the content of this slide: Published on behalf of the European Society of Cardiology.

(A, B) Representative TEM images from the skin ...

Figure 1. Flow diagram for selection of articles for systematic review. Unless provided in the caption above, the following copyright applies to the content.

Figure 1. Sequence comparison of plasmid pG38 (GenBank accession no

Figure 1. Time–kill studies for selected isolates (each line represents the average of duplicate studies). AMP, ... Figure 1. Time–kill studies for selected.

Figure 1 MIC test strips showing reversion of daptomycin resistance of isolate 5 passaged in vitro. This figure ... Figure 1 MIC test strips showing reversion.

Figure 1. Outer membrane protein profiling of parental strain KJΔDEFΔ5 and its derivative fluoroquinolone-resistant ... Figure 1. Outer membrane protein.

Figure 1. Trunk and leg fat over study period. LS, log transformed.

Unless provided in the caption above, the following copyright applies to the content of this slide: Published on behalf of the European Society of Cardiology.

Unless provided in the caption above, the following copyright applies to the content of this slide: Published on behalf of the European Society of Cardiology.

Figure 1. Colony morphology of an A. fumigatus non-WT strain and an A

Figure 1. The unique structures of the SCCmec type II element identified in ORSL strain CGMH-SL Figure 1. The unique structures of the SCCmec type.

Unless provided in the caption above, the following copyright applies to the content of this slide: Published on behalf of the European Society of Cardiology.

Figure 1. Observed mean (SD) micafungin plasma concentrations.

Supplementary Figure 5: Effect of S48168 on normalized organ and skeletal muscle weights after 12 weeks of treatment for all the experimental groups from.

Figure 1 Empa and Cariporide effects during IR in insulin-perfused hearts. Hearts were subjected to IR and 1 µM Empa, ... Figure 1 Empa and Cariporide.

Figure 2. (a) Geometric mean (%CV) tenofovir diphosphate concentrations (TFV-DP in fmol/punch) in dried blood spot ... Figure 2. (a) Geometric mean (%CV)

Figure 1. Biofilm susceptibility to antibiotic treatment

Fig. 5. Combination of SAHA and ML produces augmented suppression of cellular proliferation with impaired cell cycle progression, enhanced apoptotic.

Figure 1. Time–kill curves of M. abscessus CIP

Figure 1. Genetic context of blaNDM-21 on pNDM21_020023

Volume 113, Issue 7, Pages (October 2017)

Volume 24, Issue 2, Pages (February 2017)

Fig. 2 ODN enhances EV transfer between cells expressing TLR9.

Figure 1. Percentage of samples with MDR (a), phenotypic ESBL-producing (b), fluoroquinolone-resistant (c) and ... Figure 1. Percentage of samples with.

Figure 1. CCG and practice decile and extreme percentile (1–9, 91–99) time trends, 2011–17. This figure appears in ... Figure 1. CCG and practice decile.

PARP‐1 activity is reduced in NEDP1 KO cells

Sean P. Cullen, Conor J. Kearney, Danielle M. Clancy, Seamus J. Martin

Phage activity against Pseudomonas aeruginosa (LESB65 wild type (WT) and adapted strain NP22_2) in an artificial sputum medium (ASM) model. Phage activity.

Figure 1 ABCDE of primary prevention.2

Figure 1. Kaplan–Meier curves showing the impact of the different pretreatment HIV-1 drug resistance categories on the ... Figure 1. Kaplan–Meier curves.

Presentation transcript:

Figure 1. Oxyclozanide enhances aminoglycosides and tetracycline Figure 1. Oxyclozanide enhances aminoglycosides and tetracycline. Biofilms (24 h old) were treated for 6 h with oxyclozanide (100 μM), tobramycin (500 μM), gentamicin (100 μM), streptomycin (100 μM) or tetracycline (100 μM), alone and in combination, and the number of viable cells within the biofilms was quantified by BacTiter-Glo<sup>TM</sup>. The assay was performed at least three times in triplicate. The results represent means plus the SEM. A one-way ANOVA followed by Bonferroni’s multiple comparison post hoc test was used to determine statistical significance between the combination and each antibiotic alone (*P < 0.05). From: The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential J Antimicrob Chemother. Published online January 08, 2019. doi:10.1093/jac/dky545 J Antimicrob Chemother | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Figure 2. Oxyclozanide kills S. aureus biofilms. S Figure 2. Oxyclozanide kills S. aureus biofilms. S. aureus biofilms (24 h old) were treated with oxyclozanide (100 μM) or tobramycin (100 μM), alone and in combination, for 6 h. The number of viable cells within the biofilms was quantified by BacTiter-Glo<sup>TM</sup>. The assay was performed twice in triplicate. The results represent means plus the SEM. A two-way ANOVA followed by Bonferroni’s multiple comparison post hoc test was used to determine statistical significance between either oxyclozanide alone and tobramycin alone or the combination and tobramycin alone (*P < 0.05). From: The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential J Antimicrob Chemother. Published online January 08, 2019. doi:10.1093/jac/dky545 J Antimicrob Chemother | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Figure 3. Dose–response curve of oxyclozanide or tobramycin alone and in combination. P. aeruginosa biofilms (24 h old) were treated for 6 h with oxyclozanide or tobramycin alone and in combination, in equal molar two-fold dilutions, and the number of viable cells within the biofilms was quantified by BacTiter-Glo<sup>TM</sup>. The assay was performed at least three times in triplicate. The results represent means ± SEM. A one-way ANOVA followed by Bonferroni’s multiple comparison post hoc test was used to determine statistical significance between the combination and tobramycin alone (*P < 0.05). From: The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential J Antimicrob Chemother. Published online January 08, 2019. doi:10.1093/jac/dky545 J Antimicrob Chemother | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Figure 4. A chequerboard dilution series of oxyclozanide and tobramycin. Twenty-four hour biofilms were treated with varying combinations of oxyclozanide and tobramycin for 6 h. The number of viable cells within the biofilms was quantified by BacTiter-Glo<sup>TM</sup>. The assay was performed twice in triplicate. The results represent means ± SD. A two-way ANOVA followed by Bonferroni’s multiple comparison post hoc test was used to determine statistical significance between the combination and tobramycin alone. Shaded cells indicate significance compared with tobramycin alone (P < 0.05). From: The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential J Antimicrob Chemother. Published online January 08, 2019. doi:10.1093/jac/dky545 J Antimicrob Chemother | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Figure 5. Oxyclozanide accelerates tobramycin killing of P Figure 5. Oxyclozanide accelerates tobramycin killing of P. aeruginosa biofilms. Twenty-four hour biofilms were treated with oxyclozanide (100 μM) or tobramycin (500 μM), alone and in combination. At 0, 2, 4, 6, and 8 h, the number of viable cells within the biofilms was determined by BacTiter-Glo<sup>TM</sup>. The assay was performed at least three times in triplicate. The results represent means ± SEM. A one-way ANOVA followed by Bonferroni’s multiple comparison post hoc test was used to determine statistical significance between the combination and tobramycin alone (*P < 0.05). From: The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential J Antimicrob Chemother. Published online January 08, 2019. doi:10.1093/jac/dky545 J Antimicrob Chemother | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Figure 6. Oxyclozanide does not induce biofilm dispersal Figure 6. Oxyclozanide does not induce biofilm dispersal. Twenty-four hour biofilms were treated with oxyclozanide, tobramycin or the combination, in equal molar two-fold dilutions, for 6 h. The effect on biofilm biomass was quantified by staining with crystal violet. The experiment was performed twice in triplicate. The results represent the means plus SEM. A one-way ANOVA followed by Bonferroni’s multiple comparison post hoc test was used to determine statistical significance between tobramycin alone and the untreated control (*P < 0.05) and between the combination and tobramycin alone. NS, not significant. From: The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential J Antimicrob Chemother. Published online January 08, 2019. doi:10.1093/jac/dky545 J Antimicrob Chemother | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Figure 7. Oxyclozanide is broadly active against P. aeruginosa Figure 7. Oxyclozanide is broadly active against P. aeruginosa. Twenty-four hour biofilms were treated with oxyclozanide (100 μM) or tobramycin (500 μM), alone and in combination for 6 h. The number of viable cells within the biofilms was quantified by BacTiter-Glo<sup>TM</sup>. The assay was performed three times in triplicate. The results represent means plus the SEM. A one-way ANOVA followed by Bonferroni’s multiple comparison post hoc test was used to determine statistical significance between the combination and tobramycin alone (*P < 0.05; NS, not significant). From: The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential J Antimicrob Chemother. Published online January 08, 2019. doi:10.1093/jac/dky545 J Antimicrob Chemother | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Figure 11. Oxyclozanide sensitizes P Figure 11. Oxyclozanide sensitizes P. aeruginosa to tobramycin by depolarizing the Δψ and further permeabilizing cells. (a) (1) Tobramycin corrupts protein synthesis triggering adaptive resistance, which includes the (2) induction of RND-type efflux pumps such as MexXY-OprM, resulting in reduced accumulation of tobramycin within the cytosol.<sup>42</sup><sup>,</sup><sup>43</sup> (3) During this time, an increase in Δψ is observed driving RND-type efflux pump activity and providing temporary resistance to tobramycin. (b) (4) Oxyclozanide permeabilizes cells and (5) shuttles protons across the IM, depolarizing the Δψ. We hypothesize that both of these activities interfere with adaptive resistance (6), allowing for greater accumulation of tobramycin within cells resulting in (7) accelerated activity and increased effectiveness. OM, outer membrane; IM, inner membrane. From: The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential J Antimicrob Chemother. Published online January 08, 2019. doi:10.1093/jac/dky545 J Antimicrob Chemother | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Figure 9. Oxyclozanide induces permeabilization and depolarizes the Δψ of P. aeruginosa. Twenty-four hour biofilms were treated with oxyclozanide (100 μM) or tobramycin (500 μM), alone and in combination, for 2 h. (a) Cells were stained with TO-PRO-3 and analysed by flow cytometry to determine the number of cells that were permeabilized. (b) Cells were also stained with DiOC2(3) and analysed by flow cytometry to determine the number of cells maintaining a Δψ. Permeabilized cells were excluded from Δψ analysis. The experiment was performed two separate times in duplicate. The results are percentage averages plus the SEM. Percentage values indicate the average relative abundance of events within each gate normalized to the total number of events analysed, excluding artefacts, aggregates and debris. A one-way ANOVA followed by Dunnett’s multiple comparison post hoc test was used to determine statistical significance between each treatment and the untreated control (*P < 0.05) and oxyclozanide treatment alone was compared with tobramycin treatment alone in panel (a) (NS, not significant). A one-way ANOVA followed by Bonferroni’s multiple comparison post hoc test was used to compare tobramycin to the combination in panel (a) and (b) (*P < 0.05). From: The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential J Antimicrob Chemother. Published online January 08, 2019. doi:10.1093/jac/dky545 J Antimicrob Chemother | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Figure 8. Tobramycin combined with oxyclozanide is more effective against stationary phase cells. Twenty-hour-old stationary phase cells were treated with oxyclozanide (100 μM) or tobramycin (50 μM), alone and in combination. At 0, 2, 4, 6, 8 and 24 h post-treatment, aliquots were enumerated for cfu/mL. The experiment was performed two times in triplicate. The results represent means ± SD. From: The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential J Antimicrob Chemother. Published online January 08, 2019. doi:10.1093/jac/dky545 J Antimicrob Chemother | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Figure 10. Oxyclozanide results in increased cellular accumulation of tobramycin. Twenty-four hour biofilms grown in glass test tubes were treated for 30 min with oxyclozanide (100 μM) and Texas Red<sup>®</sup>-labelled tobramycin (250 μg/mL). After washing off the planktonic cells, the biofilms were lysed with 0.2% Triton-X 100<sup>®</sup> and relative fluorescence units with excitation at 595 nm and emission at 615 nm were measured to quantify labelled tobramycin. The assay was performed twice in duplicate. The results represent means plus the SEM. An unpaired t-test was performed comparing tobramycin versus oxyclosanide and tobramycin (*P < 0.05). From: The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential J Antimicrob Chemother. Published online January 08, 2019. doi:10.1093/jac/dky545 J Antimicrob Chemother | © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)