ArticleAntimicrobial agents and chemotherapy2015
Structural variations of the cell wall precursor lipid II and their influence on binding and activity of the lipoglycopeptide antibiotic oritavancin.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Extrapolation of oritavancin PK/PD targets to inform therapeutic drug monitoring: a systematic review.The Journal of antimicrobial chemotherapy · 2026Pooled it
- Assessing Vancomycin-Formyl Peptide Conjugate Binding to the Surface of Resistant Staphylococcus aureus via Flow Cytometry.Chembiochem : a European journal of chemical biology · 2026Article
- Rational construction of a high-quality and high-efficiency biosynthetic system and fermentation optimization for A82846B based on combinatorial strategies in Amycolatopsis orientalis.Microbial cell factories · 2024Article
- A comprehensive computational study to explore promising natural bioactive compounds targeting glycosyltransferase MurG in Escherichia coli for potential drug development.Scientific reports · 2024Article
- Insights into Peptidoglycan-Targeting Radiotracers for Imaging Bacterial Infections: Updates, Challenges, and Future Perspectives.ACS infectious diseases · 2024Review
- Screening of vancomycin resistance-associated genes in methicillin-resistantVeterinary research forum : an international quarterly journal · 2024Article
- The Clinical Efficacy of Multidose Oritavancin: A Systematic Review.Antibiotics (Basel, Switzerland) · 2023Review
- Conjugation of Vancomycin with a Single Arginine Improves Efficacy against Mycobacteria by More Effective Peptidoglycan Targeting.Journal of medicinal chemistry · 2023Article
- Molecular Basis of Non-β-Lactam Antibiotics Resistance inAntibiotics (Basel, Switzerland) · 2022Review
- Recent Advances in the Development of Semisynthetic Glycopeptide Antibiotics: 2014-2022.ACS infectious diseases · 2022Review
- Antimicrobial Mechanisms and Clinical Application Prospects of Antimicrobial Peptides.Molecules (Basel, Switzerland) · 2022Review
- The Increasing Issue of Vancomycin-Resistant Enterococci and the Bacteriocin Solution.Probiotics and antimicrobial proteins · 2020Review
- Antimicrobial resistance in methicillin-resistantAntimicrobial agents and chemotherapy · 2019Review
- Towards the Native Binding Modes of Antibiotics that Target Lipid II.Chembiochem : a European journal of chemical biology · 2019Review
- Therapeutic compounds targeting Lipid II for antibacterial purposes.Infection and drug resistance · 2019Article
- High-resolution NMR studies of antibiotics in cellular membranes.Nature communications · 2018Article
- Genome sequencing analysis of Streptomyces coelicolor mutants that overcome the phosphate-depending vancomycin lethal effect.BMC genomics · 2018Article
- First insights of peptidoglycan amidation in Gram-positive bacteria - the high-resolution crystal structure of Staphylococcus aureus glutamine amidotransferase GatD.Scientific reports · 2018Article
- Inhibition of d-Ala incorporation into wall teichoic acid in Staphylococcus aureus by desleucyl-oritavancin.Chemical communications (Cambridge, England) · 2017Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oritavancin is a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin with activity against Gram-positive pathogens, including vancomycin-resistant staphylococci and enterococci. Compared to vancomycin, oritavancin is characterized by the presence of two additional residues, a hydrophobic 4'-chlorobiphenyl methyl moiety and a 4-epi-vancosamine substituent, which is also present in chloroeremomycin. Here, we show that oritavancin and its des-N-methylleucyl variant (des-oritavancin) effectively inhibit lipid I- and lipid II-consuming peptidoglycan biosynthesis reactions in vitro. In contrast to that for vancomycin, the binding affinity of oritavancin to the cell wall precursor lipid II appears to involve, in addition to the D-Ala-D-Ala terminus, other species-specific binding sites of the lipid II molecule, i.e., the crossbridge and D-isoglutamine in position 2 of the lipid II stem peptide, both characteristic for a number of Gram-positive pathogens, including staphylococci and enterococci. Using purified lipid II and modified lipid II variants, we studied the impact of these modifications on the binding of oritavancin and compared it to those of vancomycin, chloroeremomycin, and des-oritavancin. Analysis of the binding parameters revealed that additional intramolecular interactions of oritavancin with the peptidoglycan precursor appear to compensate for the loss of a crucial hydrogen bond in vancomycin-resistant strains, resulting in enhanced binding affinity. Augmenting previous findings, we show that amidation of the lipid II stem peptide predominantly accounts for the increased binding of oritavancin to the modified intermediates ending in D-Ala-D-Lac. Corroborating our conclusions, we further provide biochemical evidence for the phenomenon of the antagonistic effects of mecA and vanA resistance determinants in Staphylococcus aureus, thus partially explaining the low frequency of methicillin-resistant S. aureus (MRSA) acquiring high-level vancomycin resistance.
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