scholarly journals Antibacterial and Anti-Virulence Effects of Furazolidone on Trueperella Pyogenes and Pseudomonas Aeruginosa

2021 ◽  
Author(s):  
Qin Chen ◽  
Kelei Zhao ◽  
Heyue Li ◽  
Kanghua Liu ◽  
Jing Li ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Molecular Basis ◽  
Inhibitory Effect ◽  
Signal Molecules ◽  
Musk Deer ◽  
Trueperella Pyogenes ◽  
Screening Experiments ◽  
Promising Strategy ◽  
Biofilm Production

Abstract Background: Trueperella pyogenes and Pseudomonas aeruginosa are two important bacterial pathogens closely relating to the occurrence and development of forest musk deer respiratory purulent disease. Although T. pyogenes is the causative agent of the disease, the subsequently invaded P. aeruginosa will predominate the infection by producing a substantial amount of quorum-sensing (QS)-controlled virulence factors, and co-infection of them usually creates serious difficulties for veterinary treatment. In order to find a potential drug that targets both T. pyogenes and P. aeruginosa, the antibacterial and anti-virulence capacities of 55 compounds, which have similar core structure to the signal molecules of P. aeruginosa QS system, were tested in this study. By performing a series of in vitro screening experiments to assess the effects of these compounds.Results: We identified that furazolidone could significantly inhibit the growth of mono-cultured T. pyogenes or in the co-culture with P. aeruginosa. Although the growth of P. aeruginosa could also be moderately inhibited by furazolidone, the results of phenotypic identification and transcriptomic analysis further revealed that furazolidone had remarkable inhibitory effect on the biofilm production, motility, and QS system of P. aeruginosa. Moreover, furazolidone could efficiently protect Caenorhabditis elegans from P. aeruginosa infection under both fast-killing and slow-killing conditions.Conclusions: This study reports the antibacterial and anti-virulence abilities of furazolidone on T. pyogenes and P. aeruginosa, and provides a promising strategy and molecular basis for the development of novel anti-infectious drugs to dealing with forest musk deer purulent disease, or other diseases caused by T. pyogenes and P. aeruginosa co-infection.

scholarly journals Inhibitory effect of propafenone derivatives on pseudomonas aeruginosa biofilm and pyocyanin production

2020 ◽  
Vol 148 (3-4) ◽  
pp. 196-202
Author(s):  
Snjezana Petrovic ◽  
Jasmina Basic ◽  
Zoran Mandinic ◽  
Dragana Bozic ◽  
Marina Milenkovic ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Laboratory Strain ◽  
Inhibitory Effect ◽  
Negative Control ◽  
Clinical Strains ◽  
Control Value ◽  
Essential Components ◽  
Pyocyanin Production

Introduction/Objective. Biofilm and pyocyanin production are essential components of Pseudomonas aeruginosa virulence and antibiotic resistance. Our objective was to examine inhibitory effect of synthetized propafenone derivatives 3-(2-Fluorophenyl)- 1-(2- (2-hydroxy-3-propylamino-propoxy)-phenyl)-propan-1-one hydrochloride (5OF) and3-(2- Trifluoromethyl-phenyl)-1-(2-(2-hydroxy-3-propylamino-propoxy)-phenyl)-propan-1-one hydrochloride (5CF3) on biofilm and pyocyanin in Pseudomonas aeruginosa clinical strains. Methods. Effects were tested on nine clinical isolates and one control laboratory strain of P. aeruginosa. In vitro analysis of biofilm growing was performed by incubating bacteria (0.5 McFarland) with 5OF and 5CF3 (500?31.2 ?g/ml) and measuring optical density (OD) at 570 nm. Bacteria in medium without compounds were positive control. Blank medium (an uninoculated medium without test compounds) was used as negative control. Pyocyanin production was estimated by OD at 520 nm, after bacteria incubated with 5CF3 and 5OF (250 and 500 ?g/ml), treated with chloroform, and chloroform layer mixed with HCl. Results. A total of 500 ?g/ml of 5OF and 5CF3 completely inhibited biofilm formation in 10/10 and 4/10 strains, respectively. A total of 250 ?g/ml of 5OF and 5CF3 strongly inhibited biofilm formation in 7/10 strains, while inhibition with 125 ?g/ml of 5OF and 5CF3 was moderate. Lower concentrations had almost no effect on biofilm production. Pyocyanin production was reduced to less than 40% of the control value in 6/9, and less than 50% of the control in 7/9 strains with 500 ?g/ml of 5OF and 5CF3, respectively. At 250 ?g/ml 5OF and 5CF3, most strains had pyocyanin production above 50% of the control value. Conclusion. Synthetized propafenone derivatives, 5OF and 5CF3, inhibited biofilms and pyocyanin production of Pseudomonas aeruginosa clinical strains. Presented results suggest that propafenone derivatives are potential lead-compounds for synthesis of novel antipseudomonal drugs.

scholarly journals Cytotoxicity of Taxol in Combination with Vincristine and Vinblastine Against A375 Cell Line

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mohammad Zandi
Keyword(s):  
Side Effects ◽  
Therapeutic Option ◽  
Inhibitory Effect ◽  
In Vitro Cytotoxicity ◽  
In Vitro Toxicity ◽  
Human Malignant Melanoma ◽  
Promising Strategy ◽  
A375 Cell Line ◽  
A375 Cells

Background: Annually, various types of cancer cause thousands of deaths globally, and identifying an appropriate therapeutic option for these disorders is of crucial importance. Side effects of anticancer drugs can be reduced through the promising strategy of combination therapy. Objectives: The present paper has investigated the in vitro cytotoxicity of Taxol, carboplatin, vinblastine, and vincristine alone and in combination against human malignant melanoma A375 cells and non-cancerous fibroblast HU2 cells to examine the possible side effects of the drugs. Methods: The cells were subjected to the examined compounds for 48 h, and the MTT test was conducted to evaluate the cytotoxicity. Results: The results indicated that the most significant effect was related to 120 μg/mL vincristine and 7.5 μg/mL Taxol+ vincristine treatments, with the survival amounts of 24 ± 0.6 and 28 ± 0%, respectively. In addition, the best 50% inhibitory effect was found to be related to Taxol + vincristine, vinblastine, and Taxol+ vinblastine treatments at the concentrations of 0.04, 2.2, and 3.4 μg/mL, respectively. Conclusions: According to the findings of in vitro toxicity, the evaluated complexes are not cytotoxic against human fibroblast HU2 cells. Also, the most significant effect on A375 cells was associated with vincristine treatment. No synergistic reaction was recorded among the different combinations of drugs based on the calculated CI values.

scholarly journals Quorum sensing and virulence of Pseudomonas aeruginosa during urinary tract infections

2012 ◽  
Vol 6 (06) ◽  
pp. 501-507 ◽  
Author(s):  
Sezgi Senturk ◽  
Seyhan Ulusoy ◽  
Gulgun Bosgelmez-Tinaz ◽  
Aysegul Yagci
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Urinary Tract Infections ◽  
Clinical Isolates ◽  
Pcr Analysis ◽  
Signal Molecules ◽  
Tract Infections

Introduction: In the opportunistic pathogen Pseudomonas aeruginosa, the production of several virulence factors depends on quorum sensing (QS) involving N-acylhomoserine lactone signal molecules. In vitro studies have suggested that the QS system is crucial in the pathogenesis of P. aeruginosa. However, it is unclear whether QS systems of P. aeruginosa play the same role during infections. Methodology:  In this study, to explore the contribution of QS systems to the pathogenesis of P. aeruginosa during urinary tract infections, we collected 82 clinical isolates. Detection of N-acyl-homoserine lactones (C12-HSL and C4-HSL) was performed on agar plates employing biosensor strains C. violaceum. Elastase and biofilm production were determined spectrophotometrically. QS genes were detected by PCR and subsequently underwent sequencing. Results and conclusion:  Six isolates were found to be negative in the production of both C12-HSL and C4-HSL and all virulence factors tested.  PCR analysis of these isolates revealed that four isolates contained all four QS genes while one isolate was negative for lasR gene, and one isolate negative for lasI, lasR and rhlR genes. Sequence analyses of these isolates showed that the lasR, lasI, rhlR and rhlI genes had point mutations. The combination of these mutations probably explains their C12-HSL, C4-HSL and virulence factor deficiencies. Results of this study suggest that QS deficient clinical isolates occur and are still capable of causing clinical infections in humans. 

scholarly journals In Vitro Activity of Human β-Defensin 2 against Pseudomonas aeruginosa in the Presence of Tear Fluid

2007 ◽  
Vol 51 (11) ◽  
pp. 3853-3860 ◽  
Author(s):  
Ling C. Huang ◽  
Rachel L. Redfern ◽  
Srihari Narayanan ◽  
Rose Y. Reins ◽  
Alison M. McDermott
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Peptide ◽  
Ocular Surface ◽  
Salt Content ◽  
Inhibitory Effect ◽  
Heat Inactivation ◽  
Binding Interaction ◽  
Cast Doubt

ABSTRACT Pseudomonas aeruginosa causes vision-threatening keratitis and is difficult to treat due to emerging resistance. Human β-defensin 2 (hBD-2) is an antimicrobial peptide expressed by ocular surface epithelia with broad-spectrum activity against various pathogens, including P. aeruginosa. The activity of hBD-2 against P. aeruginosa in the presence of human tears or NaCl was studied. In some experiments, tears were heat-inactivated, filtered, and separated into cationic/anionic fractions or mucin MUC5AC was removed by immunoprecipitation before use. Immunoprecipitation was performed to study the interaction between hBD-2 and MUC5AC. hBD-2 activity was reduced by 40 to 90% in the presence of 17.5 to 70% (vol/vol) tears. NaCl reduced hBD-2 activity, but at most it could account for only 36% of the inhibitory effect of tears. Heat inactivation and filtration attenuated the ability of tears to inhibit hBD-2 activity by 65 and 68%, respectively. Anionic tear fractions significantly reduced (86%) the activity of hBD-2, whereas only a 22% reduction was observed with the cationic fractions. In the absence of MUC5AC, the activity of hBD-2 was restored by 64%. Immunoprecipitation studies suggested that the loss of hBD-2 activity in tears is due to a direct binding interaction with MUC5AC. Our data showed that the antimicrobial activity of hBD-2 is sensitive to the presence of human tears and that this is partly due to the salt content and also the presence of MUC5AC. These data cast doubt on the effectiveness of hBD-2 as an antimicrobial peptide, and additional studies are required to conclusively elucidate its role in innate immunity at the ocular surface in vivo.

scholarly journals Inhibitory Effect of Biocides on the Viable Masses and Matrices of Staphylococcus aureus and Pseudomonas aeruginosa Biofilms

2010 ◽  
Vol 76 (10) ◽  
pp. 3135-3142 ◽  
Author(s):  
K. Toté ◽  
T. Horemans ◽  
D. Vanden Berghe ◽  
L. Maes ◽  
P. Cos
Keyword(s):  
Hydrogen Peroxide ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Sodium Hypochlorite ◽  
Peracetic Acid ◽  
Inhibitory Effect ◽  
European Guidelines ◽  
The Matrix ◽  
Antibiofilm Agents

ABSTRACT Bacteria and matrix are essential for the development of biofilms, and assays should therefore target both components. The current European guidelines for biocidal efficacy testing are not adequate for sessile microorganisms; hence, alternative discriminatory test protocols should be used. The activities of a broad range of biocides on Staphylococcus aureus and Pseudomonas aeruginosa biofilms were evaluated using such in vitro assays. Nearly all selected biocides showed a significant decrease in S. aureus biofilm viability, with sodium hypochlorite and peracetic acid as the most active biocides. Only hydrogen peroxide and sodium hypochlorite showed some inhibitory effect on the matrix. Treatment of P. aeruginosa biofilms was roughly comparable to that of S. aureus biofilms. Peracetic acid was the most active on viable mass within 1 min of contact. Isopropanol ensured a greater than 99.999% reduction of P. aeruginosa viability after at least 30 min of contact. Comparable to results with S. aureus, sodium hypochlorite and hydrogen peroxide markedly reduced the P. aeruginosa matrix. This study clearly demonstrated that despite their aspecific mechanisms of action, most biocides were active only against biofilm bacteria, leaving the matrix undisturbed. Only hydrogen peroxide and sodium hypochlorite were active on both the biofilm matrix and the viable mass, making them the better antibiofilm agents. In addition, this study emphasizes the need for updated and standardized guidelines for biofilm susceptibility testing of biocides.

Effect of Thio- and Hydrazino-derivatives of Uracil, 6-Azauracil and 6-Azathymine on the Growth of Some Microorganisms in Vitro

1972 ◽  
Vol 27 (7) ◽  
pp. 818-821 ◽  
Author(s):  
Alexander Spassov ◽  
Evgeny Golovinsky ◽  
Nadejda Spassovska ◽  
Liliana Maneva
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Bacillus Subtilis ◽  
Neurospora Crassa ◽  
Candida Tropicalis ◽  
Inhibitory Effect ◽  
Streptococcus Faecalis ◽  
Derivatives Of

The antibacterial activity of 2-thiouracil, 2-methylthiouracil, 2-hydrazinouracil, 2,4-dithiouracil, 2-thio-4-hydrazinouracil, 2-thio-6-azathymine, 2-hydrazino-6-azathymine, 2,4-dithio-6-azathymine, 2-thio-4-hydrazino-6-azathymine, 2,4-dimethylthio-6-azathymine, 2-methylthio-4-hydrazino-6-azathymine, 4-thio-6-azauracil and 4-hydrazino-6-azauracil has been studied on the growth of: Staphylococcus aureus 209, Streptococcus faecalis 775, Escherichiia coli 387, Pseudomonas aeruginosa, Bacillus subtilis, Candida tropicalis and Neurospora crassa 9863.The highest inhibitory effect was observed with 4-hydrazino-derivatives of 2-thiouracil, 6-azauracil and 2-thio-6-azathymine.

scholarly journals Contribution of Drugs Interfering with Protein and Cell Wall Synthesis to the Persistence of Pseudomonas aeruginosa Biofilms: An In Vitro Model

2021 ◽  
Vol 22 (4) ◽  
pp. 1628
Author(s):  
Gianmarco Mangiaterra ◽  
Elisa Carotti ◽  
Salvatore Vaiasicca ◽  
Nicholas Cedraro ◽  
Barbara Citterio ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cell Wall ◽  
Bacterial Population ◽  
In Vitro Model ◽  
Biofilm Production ◽  
Lung Infections ◽  
Vitro Model ◽  
High Doses

The occurrence of Pseudomonas aeruginosa (PA) persisters, including viable but non-culturable (VBNC) forms, subpopulations of tolerant cells that can survive high antibiotic doses, is the main reason for PA lung infections failed eradication and recurrence in Cystic Fibrosis (CF) patients, subjected to life-long, cyclic antibiotic treatments. In this paper, we investigated the role of subinhibitory concentrations of different anti-pseudomonas antibiotics in the maintenance of persistent (including VBNC) PA cells in in vitro biofilms. Persisters were firstly selected by exposure to high doses of antibiotics and their abundance over time evaluated, using a combination of cultural, qPCR and flow cytometry assays. Two engineered GFP-producing PA strains were used. The obtained results demonstrated a major involvement of tobramycin and bacterial cell wall-targeting antibiotics in the resilience to starvation of VBNC forms, while the presence of ciprofloxacin and ceftazidime/avibactam lead to their complete loss. Moreover, a positive correlation between tobramycin exposure, biofilm production and c-di-GMP levels was observed. The presented data could allow a deeper understanding of bacterial population dynamics during the treatment of recurrent PA infections and provide a reliable evaluation of the real efficacy of the antibiotic treatments against the bacterial population within the CF lung.

scholarly journals Wee1 Inhibitor AZD1775 Combined with Cisplatin Potentiates Anticancer Activity against Gastric Cancer by Increasing DNA Damage and Cell Apoptosis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Dongshao Chen ◽  
Xiaoting Lin ◽  
Jing Gao ◽  
Lin Shen ◽  
Zhongwu Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Damage ◽  
Cell Apoptosis ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Promising Strategy ◽  
Underlying Mechanisms ◽  
Deep Exploration

Based on the mechanisms by which Wee1 inhibitor and cisplatin played their own role, a promising strategy of Wee1 inhibitor combined with cisplatin was proposed, which was investigated in gastric cancer (GC). Either Wee1 inhibitor AZD1775 or cisplatin alone had a certain inhibitory effect on in vitro cell proliferation; however, the inhibitory effect was more significant when AZD1775 combined with cisplatin in vitro and in vivo. The underlying mechanisms unveiled that the increased DNA damage indicated by increased γH2AX protein, as well as augmented cell apoptosis indicated by upregulated proapoptotic proteins, was responsible for the significant inhibitory effect of AZD1775 plus cisplatin. Moreover, compared to any single drug, in vitro cell migration and invasion abilities were further attenuated by AZD1775 combined with cisplatin. There were suggestive results that the potentiated cytotoxicity between AZD1775 and cisplatin deserved a deep exploration in the future.

scholarly journals Microstructured Lipid Carriers (MLC) Based on N-Acetylcysteine and Chitosan Preventing Pseudomonas aeruginosa Biofilm

2021 ◽  
Vol 22 (2) ◽  
pp. 891
Author(s):  
Marta Guerini ◽  
Pietro Grisoli ◽  
Cristina Pane ◽  
Paola Perugini
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Encapsulation Efficiency ◽  
Size Range ◽  
Antioxidant Properties ◽  
Antioxidant Effect ◽  
Bacterial Biofilm ◽  
Biofilm Growth ◽  
Biofilm Production ◽  
Antioxidant Agent

The aim of this work was the development of microstructured lipid carriers (MLC) based on chitosan (CH) and containing N-acetylcysteine (NAC), a mucolytic and antioxidant agent, to inhibit the formation of Pseudomonas aeruginosa biofilm. MLC were prepared using the high shear homogenization technique. The MLC were characterized for morphology, particle size, Z potential, encapsulation efficiency and drug release. The antioxidant properties of NAC-loaded microstructured carriers were evaluated through an in vitro spectrophotometer assay. Finally, the activity of NAC-CH-MLC on biofilm production by Pseudomonas aeruginosa was also evaluated. Results obtained from this study highlighted that the use of chitosan into the inner aqueous phase permitted to obtain microstructured particles with a narrow size range and with good encapsulation efficiency. NAC-loaded MLC showed higher antioxidant activity than the free molecule, demonstrating how encapsulation increases the antioxidant effect of the molecule. Furthermore, the reduction of biofilm growth resulted extremely high with MLC being 64.74% ± 6.2% and 83.74% ± 9.95%, respectively, at 0.5 mg/mL and 2 mg/mL. In conclusion, this work represents a favorable technological strategy against diseases in which bacterial biofilm is relevant, such as cystic fibrosis.

scholarly journals Zinc Exposure Promotes Commensal-to-Pathogen Transition in Pseudomonas aeruginosa Leading to Mucosal Inflammation and Illness in Mice

2021 ◽  
Vol 22 (24) ◽  
pp. 13321
Author(s):  
Tong Wu ◽  
Annie Gagnon ◽  
Katherine McGourty ◽  
Rebecca DosSantos ◽  
Lucia Chanetsa ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Mucosal Damage ◽  
Zinc Homeostasis ◽  
Mucosal Inflammation ◽  
Zinc Intake ◽  
Biofilm Production ◽  
Excess Zinc ◽  
Zinc Exposure

The opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa) is associated gastrointestinal (GI) inflammation and illness; however, factors motivating commensal-to-pathogen transition are unclear. Excessive zinc intake from supplements is common in humans. Due to the fact that zinc exposure enhances P. aeruginosa colonization in vitro, we hypothesized zinc exposure broadly activates virulence mechanisms, leading to inflammation and illness. P. aeruginosa was treated with excess zinc and growth, expression and secretion of key virulence factors, and biofilm production were determined. Effects on invasion, barrier function, and cytotoxicity were evaluated in Caco-2 cells co-cultured with P. aeruginosa pre-treated with zinc. Effects on colonization, mucosal pathology, inflammation, and illness were evaluated in mice infected with P. aeruginosa pre-treated with zinc. We found the expression and secretion of key virulence factors involved in quorum sensing (QS), motility (type IV pili, flagella), biosurfactants (rhamnolipids), toxins (exotoxin A), zinc homeostasis (CzcR), and biofilm production, were all significantly increased. Zinc exposure significantly increased P. aeruginosa invasion, permeability and cytotoxicity in Caco-2 cells, and enhanced colonization, inflammation, mucosal damage, and illness in mice. Excess zinc exposure has broad effects on key virulence mechanisms promoting commensal-to-pathogen transition of P. aeruginosa and illness in mice, suggesting excess zinc intake may have adverse effects on GI health in humans.

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