Oritavancin Kills Stationary-Phase and Biofilm<i>Staphylococcus aureus</i>Cells In Vitro

Belley, Adam; Neesham-Grenon, Eve; McKay, Geoffrey A.; Arhin, Francis F.; Harris, Robert J.; Beveridge, Terry J.; Parr, Thomas; Moeck, Greg

doi:10.1128/aac.00766-08

Cited by 162 publications

(140 citation statements)

References 38 publications

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“…This might suggest that the strong antimicrobial activity of Van-M-02 could be attributed to high affinity not only for lipid II but also for lipid membrane. 22,28) The minimum inhibitory concentration (MIC) value of ΔN-Van-M-02 for S. aureus RN4220 was similar to that of vancomycin, and ΔN-Van-M-02 showed stronger activity against E. faecium SR7940 and SR23598 than those of vancomycin. 27) On the other hand, the affinity of ΔN-Van-M-02 to D-alanyl-D-alanine was weaker than that of vancomycin as ΔN-Van-M-02 does not have the N-terminal group which contributes to the D-alanyl-D-alanine binding pocket.…”

Section: Binding Properties Of Vancomycin and Its Analogs To The Modementioning

confidence: 99%

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Binding Properties of Antimicrobial Agents to Lipid Membranes Using Surface Plasmon Resonance

Kinouchi

Arimoto

Nishiguchi

et al. 2014

Biological & Pharmaceutical Bulletin

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In the present study, we examined the interaction of antimicrobial agents with four model lipid membranes that mimicked mammalian cell membranes and Gram-positive and -negative bacterial membranes and analyzed the binding kinetics using our surface plasmon resonance (SPR) technique. The selective and specific binding characteristics of antimicrobial agents to the lipid membranes were estimated, and the kinetic parameters were analyzed by application of a two-state reaction model. Reproducible analysis of binding kinetics was observed. Vancomyicn, teicoplanin, erythromycin, and linezolid showed little interaction with the four lipid membranes in the SPR system. On the other hand, vancomycin analogues showed interaction with the model lipid membranes in the SPR system. The selective and specific binding characteristics of vancomycin analogues to the lipid membranes are discussed based on data for in vitro antibacterial activities and our data on the binding affinity of the D-alanyl-D-alanine terminus of a pentapeptide cell wall obtained by SPR. The mechanism of antibacterial activity against Staphylococcus aureus and vancomycin-resistant enterococci could be evaluated using the binding affinity obtained with our SPR techniques. The results indicate that the SPR method could be widely applied to predict binding characteristics, such as selectivity and specificity, of many antimicrobial agents to lipid membranes. Key words surface plasmon resonance; lipid membrane; antimicrobial agent; vancomycinThe properties and mechanisms of drug interactions with biological membranes serve as critical information in the drug discovery stage to characterize the pharmacokinetics and pharmacodynamics properties of drug candidates. In particular, the affinity of antimicrobial agents for lipid membranes is one of the critical factors influencing their selectivity and potency and plays an important role in the antimicrobial mechanism of action.1-7) In order to accelerate drug discovery and development, various in vitro analytical techniques, such as circular dichroism spectroscopy, fluorescence spectroscopy, differential scanning calorimetry, nuclear magnetic resonance, and fluorescence resonance energy transfer, have been employed. [8][9][10]

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Section: Binding Properties Of Vancomycin and Its Analogs To The Modementioning

confidence: 99%

“…27) Some glycopeptide antibiotics are known to perturb bacterial cell membrane potential and permeability. 22,28) Therefore, the affinity of antibacterial agents for the lipid membranes was investigated, combining the two data sets on antibacterial activities.…”

mentioning

confidence: 99%

Binding Properties of Antimicrobial Agents to Lipid Membranes Using Surface Plasmon Resonance

Kinouchi

Arimoto

Nishiguchi

et al. 2014

Biological & Pharmaceutical Bulletin

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“…These techniques have previously been used to investigate the membrane-activity of daptomycin [15] , chlorhexidine [16] , ceragenins [13] , telavancin [17] and oritavancin [18] in which it was determined that these antimicrobials have a direct action on bacterial membranes, resulting in membrane disruption, loss of membrane integrity and release of intracellular constituents.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Action of a Membrane-Active Quinoline-Based Antimicrobial on Natural and Model Bacterial Membranes

et al. 2017

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self-assembled monolayers; SLD, scattering length density; SMW, silicon matched water; SSI, surgical site infections; SRS, standard reaction solution; TMPA, 3-(trimethoxysilyl)propyl acrylate; TSA, tryptone soya agar. ABSTRACTHT61 is a quinoline-derived antimicrobial, which exhibits bactericidal potency against both multiplying and quiescent methicillin resistant and sensitive Staphylococcus aureus, and has been proposed as an adjunct for other antimicrobials in order to extend their usefulness in the face of increasing antimicrobial resistance. In this study we have examined HT61's effect on the permeability of Staphylococcus aureus membranes and whether this putative activity can be attributed to an interaction with lipid bilayers. Using membrane potential and ATP release assays, we have shown that HT61 disrupts the membrane enough to results in depolarisation of the membrane and release of intercellular constituents at concentrations above and below the minimum inhibitory concentration of the drug. Utilising both monolayer subphase injection and neutron reflectometry we have shown that increasing the anionic lipid content of the membrane leads to a more marked effect of the drug. In bilayers containing 25 mol% phosphatidylglycerol, neutron reflectometry data suggests that exposure to HT61 increases the level of solvent in the hydrophobic region of the membrane, which is indicative of gross structural damage. Increasing the proportion of PG elicits a concomitant level of membrane damage resulting in almost total destruction when 75 mol% phosphatidylglycerol is present.We therefore propose that HT61's primary action is directed towards the cytoplasmic membrane of Gram positive bacteria.The quinoline-derived cationic antimicrobial HT61 [1] was initially developed to improve the success of nasal decolonisation interventions aimed at decreasing the risk of post-operative surgical site infections (SSI) posed by carriage of methicillin resistant Staphylococcus aureus (MRSA) [2,3] . However, more recently it has been proposed as a resistance breaker to be used in conjunction with other more established antimicrobials [4] . Although the protein synthesis inhibitor mupirocin is currently widely used for anti-MRSA nasal decolonisation, it is not active against non-multiplying persister bacteria which constitute a reservoir for recolonisation [5] . In addition to this, an increased prevalence of mupirocin resistant MRSA [6] has led to the development of more effective alternatives, including the experimental antimicrobials LTX-109 [7] and XF-73 [8] in addition to HT61 [1] .The mode of action of HT61 has not hitherto been thoroughly investigated, however initial cell-based assays showed that HT61 is capable of depolarising the cytoplasmic membrane ofGram positives with further evidence from electron microscopy suggesting that HT61 causes lysis of either the membrane or cell wall [1,4] . The putative membrane-targeting of HT61 may provide some explanation for its potency against non-multiplying MRSA [9] , and suggests that...

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“…Against static biofilms grown on plastic pegs and made of methicillin-sensitive S. aureus (MSSA), MRSA or VISA, oritavancin was effective at minimal biofilm eradication concentrations (MBECs) ranging between 0.5 and 8 mg/L, which are only 1 dilution higher than the MICs [63]. Telavancin activity has been investigated in a wide range of biofilm models, including in vitro static and dynamic models with MSSA, MRSA, VISA, or even enterococci [64][65][66] as well as animal models (see Chan et al [67] for an indepth review on this specific topic).…”

Section: In Vitro Models Of Persistent Infectionsmentioning

confidence: 99%

Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review

Bambeke

2015

Drugs

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Oritavancin, telavancin, and dalbavancin are recently marketed lipoglycopeptides that exhibit remarkable differences to conventional molecules. While dalbavancin inhibits the late stages of peptidoglycan synthesis by mainly impairing transglycosylase activity, oritavancin and telavancin anchor in the bacterial membrane by the lipophilic side chain linked to their disaccharidic moiety, disrupting membrane integrity and causing bacteriolysis. Oritavancin keeps activity against vancomycin-resistant enterocococci, being a stronger inhibitor of transpeptidase than of transglycosylase activity. These molecules have potent activity against Grampositive organisms, most notably staphylococci (including methicillin-resistant Staphylococcus aureus and to some extent vancomycin-intermediate S. aureus), streptococci (including multidrug-resistant pneumococci), and Clostridia. All agents are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin, for hospitalacquired and ventilator-associated bacterial pneumonia. While telavancin is administered daily at 10 mg/kg, the remarkably long half-lives of oritavancin and dalbavancin allow for infrequent dosing (single dose of 1200 mg for oritavancin and 1000 mg at day 1 followed by 500 mg at day 8 for dalbavancin), which could be exploited in the future for outpatient therapy. Among possible safety issues evidenced during clinical development were an increased risk of developing osteomyelitis with oritavancin; taste disturbance, nephrotoxicity, and risk of corrected QT interval prolongation (especially in the presence of at-risk co-medications) with telavancin; and elevation of hepatic enzymes with dalbavancin. Interference with coagulation tests has been reported with oritavancin and telavancin. These drugs proved non-inferior to conventional treatments in clinical trials but their advantages may be better evidenced upon future evaluation in more severe infections. Key PointsNew lipoglycopeptides (telavancin, oritavancin, dalbavancin) differ from vancomycin by the presence of a lipophilic side chain, which profoundly modifies their pharmacokinetic and/or pharmacodynamic profile.Among these agents, telavancin and oritavancin have multiple modes of action and are highly bactericidal.Oritavancin and dalbavancin have prolonged halflives, allowing for their use a single-dose or twodose (once-a-week) regimen, respectively. These three drugs are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin is indicated for hospital-acquired and ventilator-associated bacterial pneumonia.

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Oritavancin Kills Stationary-Phase and BiofilmStaphylococcus aureusCells In Vitro

Cited by 162 publications

References 38 publications

Binding Properties of Antimicrobial Agents to Lipid Membranes Using Surface Plasmon Resonance

Binding Properties of Antimicrobial Agents to Lipid Membranes Using Surface Plasmon Resonance

Mechanism of Action of a Membrane-Active Quinoline-Based Antimicrobial on Natural and Model Bacterial Membranes

Lipoglycopeptide Antibacterial Agents in Gram-Positive Infections: A Comparative Review

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