Efficacy of NZ2114, a Novel Plectasin-Derived Cationic Antimicrobial Peptide Antibiotic, in Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

Xiong, Yan Q.; Hady, Wessam Abdel; Deslandes, Antoine; Rey, Astrid; Fraisse, Laurent; Kristensen, Hans-Henrik; Yeaman, Michael R.; Bayer, Arnold S.

doi:10.1128/aac.00453-11

Cited by 61 publications

(55 citation statements)

References 27 publications

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“…We referenced the previous studies to determine the induction method of the colitis model (34)(35)(36) and a rough dose range of peptide first (36)(37)(38)(39)(40)(41)(42). We found that providing drinking water containing DSS induces colitis was one of the well-established experimental models for studying IBD (43).…”

Section: Discussionmentioning

confidence: 99%

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Han¹,

Zhang

Xia

et al. 2015

The Journal of Immunology

140

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Intestinal permeability plays a critical role in the etiopathogenesis of ulcerative colitis. Defensins, including porcine β-defensin (pBD)2, are crucial antimicrobial peptides for gut protection owing to their antibacterial and immunomodulatory activities. The purpose of this study was to investigate the protective effects of pBD2 on mucosal injury and the disruption of the epithelial barrier during the pathological process of dextran sodium sulfate (DSS)–induced colitis. The effects and mechanism of pBD2 were evaluated both using a DSS-induced C57BL/6 mouse model and, in vitro, using Caco-2 and RAW264.7 cells. DSS-induced colitis was characterized by higher disease activity index, shortened colon length, elevated activities of myeloperoxidase and eosinophil peroxidase, histologic evidence of inflammation, and increased expression levels of TNF-α, IL-6, and IL-8. pBD2 increased the expression of zonula occludens-1, zonula occludens-2, claudin-1, mucin-1, and mucin-2 mRNA and proteins, and it decreased permeability to FITC-D, as well as apoptosis, in DSS-treated mice. pBD2 also decreased inflammatory infiltrates of the colon epithelium. In Caco-2 cells, pBD2 increased transepithelial electrical resistance and mucin mRNA expression, and it decreased the permeability of FITC-D while preserving the structural integrity of the tight junctions. The effects of pBD2 appeared to be through upregulation of the expression of genes associated with tight junctions and mucins, and by suppressing DSS-induced increases in inflammation, inducible NO synthase, cyclooxygenase-2, and apoptosis. These results show that pBD2 improves DSS-induced changes in mucosal lesions and paracellular permeability, possibly by affecting the activation of NF-κB signaling. The present study demonstrates that intrarectal administration of pBD2 may be a novel preventive option for ulcerative colitis.

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Section: Discussionmentioning

confidence: 99%

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Han¹,

Zhang

Xia

et al. 2015

The Journal of Immunology

140

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“…Plectasin NZ2114 has previously shown promising results in the treatment of various S. aureus diseases in vivo (6,7). Using this antimicrobial peptide as an active loading agent in a novel IPN-based device material showed promising results in a comprehensive in vitro test procedure, accounting for several relevant factors that influence the performance of the catheter in vivo.…”

mentioning

confidence: 99%

Controlled Release of Plectasin NZ2114 from a Hybrid Silicone-Hydrogel Material for Inhibition of Staphylococcus aureus Biofilm

Klein

Grønnemose

Alm³

et al. 2017

Antimicrob Agents Chemother

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Staphylococcus aureus is a major human pathogen in catheter-related infections. Modifying catheter material with interpenetrating polymer networks is a novel material technology that allows for impregnation with drugs and subsequent controlled release. Here, we evaluated the potential for combining this system with plectasin derivate NZ2114 in an attempt to design an S. aureus biofilm-resistant catheter. The material demonstrated promising antibiofilm properties, including properties against methicillin-resistant S. aureus, thus suggesting a novel application of this antimicrobial peptide.

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“…Other methods determined VAN in rabbit serum, but the sensitivity of these assays was insufficient [10] [11]. Compared to these assays, the current method has good sensitivity and to our knowledge, it is the first UHPLC-MS/MS method to quantify VAN in rabbit serum using only 2 µL of sample.…”

Section: Resultsmentioning

confidence: 98%

“…There are assays available in the literature to determine VAN in rabbit serum [10] [11]; however, there have been no attempts to quantify VAN in rabbit serum using LC-MS/MS. The objective of this study was to develop a sensitive and selective ultra-high performance LC-MS/MS (UHPLC-MS/MS) method for the quantification of trace levels of VAN in rabbit serum requiring a low sample volume.…”

Section: Introductionmentioning

confidence: 99%

An Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Vancomycin Requiring Only 2 µL of Rabbit Serum

Schmitt¹,

Szeitz²,

Klassen³

et al. 2017

AJAC

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A highly sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the quantification of vancomycin (VAN) in low volumes of rabbit serum. For each analysis, 2 µL of rabbit serum was precipitated with methanol that contained the internal standard teicoplanin (TEI). The supernatant was transferred into a 384 well-plate, diluted with water, covered with a pierceable silicone mat and 5 µL was analyzed in positive ionization mode. The UHPLC-MS/MS consisted of an Agilent 1290 Infinity UHPLC system connected to an AB Sciex QTrap ® 5500 hybrid linear ion-trap triple quadrupole mass spectrometer equipped with a Turbo Spray source. Chromatographic separation was achieved using a Waters Acquity UPLC BEH C 18 (1.7 µm, 2.1 mm × 100 mm) column, a VanGuard (1.7 µm, 2.1 × 5 mm) guard column and a mobile phase of water and methanol both containing 5 mM ammonium acetate with 0.1% formic acid. VAN was quantified with multiple reaction monitoring using the transitions of m/z 725.5/144.2, and TEI was monitored at m/z 940.6/316.4. The accuracy, precision, linearity, range and lower limit of quantification (LLOQ) were determined. The accuracy was ≤9.93% and the precision was ≤10.6%. The range was established as 0.1 to 40 µg•mL −1 . The LLOQ was 0.1 µg•mL −1 VAN requiring 2 µL of sample with an accuracy of −20.2% and precision of 8.39%. The method was applied successfully to determine the VAN concentrations in rabbit serum after the i.v. administration of VAN.

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Efficacy of NZ2114, a Novel Plectasin-Derived Cationic Antimicrobial Peptide Antibiotic, in Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

Cited by 61 publications

References 27 publications

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Controlled Release of Plectasin NZ2114 from a Hybrid Silicone-Hydrogel Material for Inhibition of Staphylococcus aureus Biofilm

An Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Vancomycin Requiring Only 2 µL of Rabbit Serum

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Efficacy of NZ2114, a Novel Plectasin-Derived Cationic Antimicrobial Peptide Antibiotic, in Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

Cited by 61 publications

References 27 publications

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Controlled Release of Plectasin NZ2114 from a Hybrid Silicone-Hydrogel Material for Inhibition of Staphylococcus aureus Biofilm

An Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Vancomycin Requiring Only 2 &#181;L of Rabbit Serum

Contact Info

Product

Resources

About

An Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Vancomycin Requiring Only 2 µL of Rabbit Serum