Glycopeptide Antibiotics

Sarkar, Paramita; Haldar, Jayanta

doi:10.1002/9781119282549.ch4

Cited by 9 publications

(5 citation statements)

References 66 publications

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“…Another natural product glycopeptide antibiotic, teicoplanin, is produced by Actinoplanes teichomyceticus and was approved for use in 1998. Industrial semi‐synthetic efforts have led to development of next‐generation glycopeptides or their lipidated analogs, lipoglycopeptides, including telavancin, dalbavancin, and oritavancin …”

Section: Introductionmentioning

confidence: 99%

“…Industrial semi-synthetic efforts have led to development of next-generation glycopeptides or their lipidated analogs, lipoglycopeptides, including telavancin, dalbavancin, and oritavancin. [4][5][6] The mode of action of vancomycin and other glycopeptide antibiotics is in binding to the terminal D-Ala-D-Ala moiety of un-crosslinked Lipid II (undecaprenyldiphospho-N-acetylmuramoyl-[N-acetylglucosamine]-L-alanyl-γ-D-glutamyl-L-lysyl-D-alanyl-D-alanine), an intermediate in the peptidoglycan layer maturation process 4,7 (Figure 1a). This binding obstructs the activity of penicillin-binding proteins (PBPs) to cross-link Lipid II into mature peptidoglycan and thus compromises the integrity of the cell envelope, leading to osmotic stress and bursting of the cell (Figure 1b).…”

Section: Introductionmentioning

confidence: 99%

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Molecular mechanisms of vancomycin resistance

2020

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Vancomycin and related glycopeptides are drugs of last resort for the treatment of severe infections caused by Gram‐positive bacteria such as Enterococcus species, Staphylococcus aureus, and Clostridium difficile. Vancomycin was long considered immune to resistance due to its bactericidal activity based on binding to the bacterial cell envelope rather than to a protein target as is the case for most antibiotics. However, two types of complex resistance mechanisms, each comprised of a multi‐enzyme pathway, emerged and are now widely disseminated in pathogenic species, thus threatening the clinical efficiency of vancomycin. Vancomycin forms an intricate network of hydrogen bonds with the d‐Ala‐d‐Ala region of Lipid II, interfering with the peptidoglycan layer maturation process. Resistance to vancomycin involves degradation of this natural precursor and its replacement with d‐Ala‐d‐lac or d‐Ala‐d‐Ser alternatives to which vancomycin has low affinity. Through extensive research over 30 years after the initial discovery of vancomycin resistance, remarkable progress has been made in molecular understanding of the enzymatic cascades responsible. Progress has been driven by structural studies of the key components of the resistance mechanisms which provided important molecular understanding such as, for example, the ability of this cascade to discriminate between vancomycin sensitive and resistant peptidoglycan precursors. Important structural insights have been also made into the molecular evolution of vancomycin resistance enzymes. Altogether this molecular data can accelerate inhibitor discovery and optimization efforts to reverse vancomycin resistance. Here, we overview our current understanding of this complex resistance mechanism with a focus on the structural and molecular aspects.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of vancomycin resistance

2020

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“…Vancomycin, a lipopeptide antibiotic approved by Food and Drug Administration of the United States in 1958 found in recent years that the MRSA isolates are resist to it [52]. Vancomycin works by binding to bacterial cell envelopes and inhibiting their cell wall synthesis instead of targeting protein like other antibiotics [53].…”

Section: Resistance To Vancomycinmentioning

confidence: 99%

Mechanistic Insights of Drug Resistance in Staphylococcus aureus with Special Reference to Newer Antibiotics

Singh¹,

Kaur²,

Mohana³

et al. 2021

Insights Into Drug Resistance in Staphylococcus Aureus

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Staphylococcus aureus is the most ubiquitous microorganism in both environment as well as animals and exists as commensal and pathogenic bacterium. In past few years it has been emerged as a superbug causing serious burden on healthcare system. This bacterium has been found to be the most resistant one toward most of the antibiotics due to its rapid structural and genetic modifications. This chapter will shed light on various types of molecular mechanisms responsible for resistance of Staphylococcus aureus showcasing how it has been emerged as a superbug. Moreover, the recent approaches which include exploring of different drug targets keeping in view the structural and functional behavior of the Staphylococcus aureus has also been discussed.

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“…Oritavancin also binds to the bridging pentaglycyl peptide of the peptidoglycan, thus significantly inhibiting transpeptidation. 6 These enhanced properties make the second generation of glycopeptides more potent than the natural glycopeptides.…”

Section: Introductionmentioning

confidence: 99%