Polymyxins Revisited

Landman, David; Georgescu, Claudiu; Martin, Don Antonio; Quale, John

doi:10.1128/cmr.00006-08

Cited by 538 publications

(492 citation statements)

References 167 publications

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“…This lack of new antimicrobials to replace those that become ineffective brings added urgency to the need to protect the efficacy of existing drugs. In the last few years there has been a resurgence of old antibiotics, and specially polymyxins discovered in the 1940s [6], as drugs of last resort for the treatment of infections caused by multi-drug resistant Gram-negative pathogens, despite their toxicity (nephro-and neurotoxicity) and the lack of clinical efficacy data [7,8]. Polymyxins belong to the class of antimicrobial peptides (AMPs), a class of antibiotics that have attracted great interest in the last few years because they rarely spur the development of resistant organisms.…”

Section: Introductionmentioning

confidence: 99%

Membrane interaction of a new synthetic antimicrobial lipopeptide sp-85 with broad spectrum activity

Grau-Campistany

Pujol

Marqués

et al. 2015

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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ARTICLE IN PRESS• Sp-85 is a new synthetic antibiotic lipopeptide with broad spectrum activity.• Pressure-area curves of mixed monolayers show non-ideal mixing.• Binding to anionic liposomes results in fusion and leakage of aqueous contents.• TEM images of antibiotic-exposed bacteria show damaged membranes.• A mechanism of action based on bacterial membrane destabilization is proposed.g r a p h i c a l a b s t r a c t a r t i c l e i n f o a b s t r a c tAntimicrobial peptides offer a new class of therapeutic agents to which bacteria may not be able to develop genetic resistance, since their main activity is in the lipid component of the bacterial cell membrane. We have developed a series of synthetic cationic cyclic lipopeptides based on natural polymyxin, and in this work we explore the interaction of sp-85, an analog that contains a C12 fatty acid at the N-terminus and two residues of arginine. This analog has been selected from its broad spectrum antibacterial activity in the micromolar range, and it has a disruptive action on the cytoplasmic membrane of bacteria, as demonstrated by TEM. In order to obtain information on the interaction of this analog with membrane lipids, we have obtained thermodynamic parameters from mixed monolayers prepared with POPG and POPE/POPG (molar ratio 6:4), as models of Gram positive and Gram negative bacteria, respectively. Langmuir-Blodgett films have been extracted on glass plates and observed by confocal microscopy, and images are consistent with a strong destabilizing effect on the membrane organization induced by sp-85. The effect of sp-85 on the membrane is confirmed with unilamelar lipid vesicles of the same composition, where biophysical experiments based on fluorescence are indicative of membrane fusion and permeabilization starting at very low concentrations of peptide and only if anionic lipids are present. Overall, results described here provide strong evidence that the mode of action of sp-85 is the alteration of the bacterial membrane permeability barrier.

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Section: Introductionmentioning

confidence: 99%

Membrane interaction of a new synthetic antimicrobial lipopeptide sp-85 with broad spectrum activity

Grau-Campistany

Pujol

Marqués

et al. 2015

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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“…(26,27) Unfortunately, there is very limited clinical experience regarding the treatment of patients infected with carbapenemase producing Enterobacteriaceae. (28) Only two classes of drugs, polymyxins and glycylcyclines have shown to have good in vitro activity against NDM-1 producers. (29) This may further lead us to reconsider the potential role of gene mutations in Class 1 integrons that may be involved in developing multi-drug resistance or even extremely drug resistant bacterial strains.…”

Section: Introductionmentioning

confidence: 99%

Emergence of Potential Superbug Mycobacterium Tuberculosis , Lessons from New Delhi Mutant-1 Bacterial Strains

Nazir

Abraham

Islam

2012

IJHS

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“…It is currently reserved for the treatment of multiresistant bacteria to other antibiotics (4)(5)(6) .…”

Section: Introductionmentioning

confidence: 99%

Nephrotoxicity Of Polymyxin B: Experimental Study In Cells And Implications For Nursing Practice

Neiva

Borges

Watanabe

et al. 2014

Rev. esc. enferm. USP

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RESUMENEl objetivo del estudio fue caracterizar los mecanismos de daño celular implicado en la fisiopatología de la citotoxicidad de la polimixina B en las células tubulares proximales (LLC-PK1) y discutir las propuestas de intervención de enfermería para identificar a los pacientes de riesgo y considerar la prevención o el tratamiento de la lesión renal aguda nefrotóxica. Corresponde a un estudio experimental cuantitativo in vitro, en el cual las células fueron expuestas a sulfato de polimixina B. La viabilidad celular se determinó por exclusión de los colorantes fluorescentes y el método morfológico con la visualización de cuerpos apoptóticos a la microscopía de fluorescencia. Las células expuestas a polimixina B demostraron reducción de la viabilidad, aumento de célu-las apoptóticas y mayor concentración de la enzima lactato deshidrogenasa. La administración de polimixina B in vitro demostró la necesidad de realizar acciones en la práctica clínica para minimizar los efectos adversos como la nefrotoxicidad. DESCRIPTORESPolimixina B Antibacterianos Lesión renal aguda Células LLC-PK1 Atención de enfermería RESUMOO objetivo do estudo foi caracterizar os mecanismos de lesão celular envolvidos na fisiopatologia da citotoxicidade da polimixina B em células tubulares proximais (LLC-PK1) e discutir as proposições de intervenção do enfermeiro para identificar os pacientes de risco e considerar a prevenção ou o tratamento para lesão renal nefrotóxica. Estudo experimental in vitro, onde as células foram expostas ao sulfato de polimixina B. A viabilidade celular foi determinada pela exclusão dos corantes fluorescentes e o método morfológico com visualização de corpos apoptóticos à microscopia de fluorescência. As células expostas à polimixina B apresentaram redução de viabilidade, aumento do número de células em apoptose e maior concentração da enzima desidrogenase láctea. A administração de polimixina B in vitro demonstrou a necessidade de ações na prática clínica para minimizar os efeitos adversos como a nefrotoxicidade. DESCRITORESPolimixina B Antibacterianos Lesão renal aguda Células LLC-PK1 Cuidados de enfermagem ABSTRACTThe aim of the study was to characterize the cell damage mechanisms involved in the pathophysiology of cytotoxicity of polymyxin B in proximal tubular cells (LLC -PK1) and discuss about the nurses interventions to identify at risk patients and consider prevention or treatment of nephrotoxicity acute kidney injury. This is a quantitative experimental in vitro study, in which the cells were exposed to 375μM polymyxin B sulfate concentration. Cell viability was determined by exclusion of fluorescent dyes and morphological method with visualization of apoptotic bodies for fluorescence microscopy. Cells exposed to polymyxin B showed reduced viability, increased number of apoptotic cells and a higher concentration of the enzyme lactate dehydrogenase. The administration of polymyxin B in vitro showed the need for actions to minimize adverse effects such as nephrotoxicity.

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Polymyxins Revisited

Cited by 538 publications

References 167 publications

Membrane interaction of a new synthetic antimicrobial lipopeptide sp-85 with broad spectrum activity

Membrane interaction of a new synthetic antimicrobial lipopeptide sp-85 with broad spectrum activity

Emergence of Potential Superbug Mycobacterium Tuberculosis , Lessons from New Delhi Mutant-1 Bacterial Strains

Nephrotoxicity Of Polymyxin B: Experimental Study In Cells And Implications For Nursing Practice

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