Locations of the Hydrophobic Side Chains of Lipoglycopeptides Bound to the Peptidoglycan of <i>Staphylococcus aureus</i>

Kim, Sung Joon; Tanaka, Kelly S.E.; Dietrich, Evelyne; Far, Adel Rafai; Schaefer, Jacob

doi:10.1021/bi400054p

Cited by 36 publications

(50 citation statements)

References 32 publications

(188 reference statements)

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“…Recently developed glycopeptide antibiotics show antimicrobial activity against vancomycin-resistant bacteria by interaction with other targets (lipid membrane, membrane protein (e.g., penicillin-binding protein 2) and cell-wall peptidoglycan), in addition to affinity for the D-alanyl-D-lactate residue. 41,42) In the present study, we found that Van-M-02 and ΔN-Van-M-02 showed antibacterial activities by interaction with the lipid membrane of vancomycin-resistant bacteria.…”

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

confidence: 48%

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 Modesupporting

confidence: 48%

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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“…61 Multiple mechanisms of action, in addition to Lipid II binding, are proposed to increase the effectiveness of 4. [62][63][64][65][66][67] Tedizolid phosphate (5) (Sivextro, torezolid phosphate, TR-701, DA-7218) is an oxazolidinone prodrug that is dephosphorylated in vivo. It was approved by the FDA in June 2014 and in EU in June 2015 for the treatment of G+ve ABSSSI, [68][69][70] and is currently in a phase-III trial for the treatment of presumed G+ve hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) (NCT02019420).…”

Section: Antibacterial Drugs Launched Since 2000mentioning

confidence: 99%

Antibiotics in the clinical pipeline at the end of 2015

2016

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There is growing global recognition that the continued emergence of multidrug-resistant bacteria poses a serious threat to human health. Action plans released by the World Health Organization and governments of the UK and USA in particular recognize that discovering new antibiotics, particularly those with new modes of action, is one essential element required to avert future catastrophic pandemics. This review lists the 30 antibiotics and two β-lactamase/β-lactam combinations first launched since 2000, and analyzes in depth seven new antibiotics and two new β-lactam/β-lactamase inhibitor combinations launched since 2013. The development status, mode of action, spectra of activity and genesis (natural product, natural product-derived, synthetic or protein/mammalian peptide) of the 37 compounds and six β-lactamase/β-lactam combinations being evaluated in clinical trials between 2013 and 2015 are discussed. Compounds discontinued from clinical development since 2013 and new antibacterial pharmacophores are also reviewed.

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“…NMR methods were used previously to examine the influence of vancomycin on cell-wall composition (15) and to determine the mode of action of the recently FDA-approved oritavancin (Orbactiv; The Medicines Company) by examining changes among key peptidoglycan cross-links and peptidoglycan precursors (18). Specific internuclear distance measurements using rotational-echo double resonance (REDOR) NMR were also employed to develop atomic-level models of antibiotic-cell wall complexes, particularly for oritavancin and related analogs, and permitted the generation of structureactivity relationships to correlate antibiotic efficacy with structural mapping in the cell wall (18)(19)(20)(21)(22)(23). All of these studies were performed using selectively labeled samples to identify key nuclei of interest.…”

Section: Introductionmentioning

confidence: 99%

Spectral Snapshots of Bacterial Cell-Wall Composition and the Influence of Antibiotics by Whole-Cell NMR

Nygaard

Romaniuk

Rice

et al. 2015

Biophysical Journal

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Gram-positive bacteria surround themselves with a thick cell wall that is essential to cell survival and is a major target of antibiotics. Quantifying alterations in cell-wall composition are crucial to evaluating drug modes of action, particularly important for human pathogens that are now resistant to multiple antibiotics such as Staphylococcus aureus. Macromolecular and whole-cell NMR spectroscopy allowed us to observe the full panel of carbon and nitrogen pools in S. aureus cell walls and intact whole cells. We discovered that one-dimensional (13)C and (15)N NMR spectra, together with spectroscopic selections based on dipolar couplings as well as two-dimensional spin-diffusion measurements, revealed the dramatic compositional differences between intact cells and cell walls and allowed the identification of cell-wall signatures in whole-cell samples. Furthermore, the whole-cell NMR approach exhibited the sensitivity to detect distinct compositional changes due to treatment with the antibiotics fosfomycin (a cell-wall biosynthesis inhibitor) and chloramphenicol (a protein synthesis inhibitor). Whole cells treated with fosfomycin exhibited decreased peptidoglycan contributions while those treated with chloramphenicol contained a higher percentage of peptidoglycan as cytoplasmic protein content was reduced. Thus, general antibiotic modes of action can be identified by profiling the total carbon pools in intact whole cells.

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Locations of the Hydrophobic Side Chains of Lipoglycopeptides Bound to the Peptidoglycan of Staphylococcus aureus

Cited by 36 publications

References 32 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

Antibiotics in the clinical pipeline at the end of 2015

Spectral Snapshots of Bacterial Cell-Wall Composition and the Influence of Antibiotics by Whole-Cell NMR

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