Iodinated vancomycin and mucopeptide biosynthesis by cell-free preparations from <i>Micrococcus lysodeikticus</i>

C, Bordet; Perkins, H. R.

doi:10.1042/bj1190877

Cited by 16 publications

(12 citation statements)

References 19 publications

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“…It can be assumed that they are either precursors in the biosynthesis of insoluble polymers or degradation products resulting from the action of lytic enzymes and particularly of endopeptidases contained in membrane preparations. This last hypothesis seems likely since the formation of soluble peptidoglycans increases more rapidly than the formation of insoluble peptidoglycans with the time of incubation (3).…”

Section: Resultsmentioning

confidence: 99%

“…Particulate enzyme was prepared by grinding the cells with three times their wet weight of levigated alumina as previously described (3). The broken cells were suspended into 50 mM Tris-hydrochloride buffer, pH 7.5, containing 0.1 M MgCl, and 1 mM 2-mercaptoethanol (15 ml/g of cells, wet weight) and centrifuged twice at 10,000 x g for 10 min.…”

Section: Preparation Of Udpmurnac-l-mentioning

confidence: 99%

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Peptidoglycans synthesized by a membrane preparation of Micrococcus luteus

Pellon¹,

C²,

Michel³

1976

J Bacteriol

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By incubation of cell-free particulate preparations from Micrococcus luteus with nucleotidic precursors uridine 5'-diphosphate-N-acetylglucosamine and uridine 5'-diphosphate-N-acetylmuramic acid-L-Ala-D-iso-Glu-L-Lys-D-Ala-D-Ala, several types of peptidoglycans were obtained: soluble peptidoglycan, insoluble peptidoglycan bound to the membrane and solubilized by trypsin, and peptidoglycan, which remained insoluble after the action of trypsin. The structure of each type of peptidoglycan was studied by action of lytic enzymes and separation of the fragments on Sephadex. Soluble peptidoglycans consist of a mixture of un-cross-linked polymers of various molecular weights. Trypsinsolubilized peptidoglycans are also a mixture of polymers of various sizes. They contain a preponderance of un-cross-linked material and some bridges with dimer peptides. Insoluble peptidoglycans, after the action of trypsin, contain about 50% of un-cross-linked peptide residues; in the other moiety, peptide units are cross-linked by D-Ala-L-Lys and D-Ala-L-Ala bonds which characterize the natural peptidoglycan. Therefore, the cell-free particulate preparation possesses the whole enzymatic system necessary for synthesis of cross-linked peptidoglycan.

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Section: Resultsmentioning

confidence: 99%

Section: Preparation Of Udpmurnac-l-mentioning

confidence: 99%

Peptidoglycans synthesized by a membrane preparation of Micrococcus luteus

Pellon¹,

C²,

Michel³

1976

J Bacteriol

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“…Vancomycin, on the other hand, functions by binding to the Cterminal sequence D ‐Ala‐ D ‐Ala of lipid II, thereby impeding further processing of the monomeric unit into peptidoglycan 17, 18. However, vancomycin and moenomycin cannot penetrate the bacterial cell membrane, so they don't encounter MurG in vivo because MurG localizes on the cytoplasmic side of the cell membrane 19, 20. We reasoned that they probably would function as inhibitors of MurG in vitro since moenomycin might interfere with the enzyme and vancomycin would bind to the peptide portion of lipid I as well.…”

Section: Resultsmentioning

confidence: 99%

Acceptor Specificity and Inhibition of the Bacterial Cell‐Wall Glycosyltransferase MurG

et al. 2003

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A continuous fluorescence coupled enzyme assay was developed to study the acceptor specificity of the glycosyltransferase MurG toward different lipid I analogues with various substituents replacing the undecaprenyl moiety. It was found that most lipid I analogues are accepted as substrates and, amongst these, the saturated C14 analogue exhibits the best activity. This substrate was used to evaluate the inhibition activity of such antibiotics as moenomycin, vancomycin, and two chlorobiphenyl vancomycin derivatives. A vancomycin derivative with a chlorobiphenyl moiety on the aglycon section was identified as a potent inhibitor of MurG.

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“…This suggested interference with the transglycosylation step of peptidoglycan assembly. Distribution studies with iodinated vancomycin showed that binding was surface-localized in the bacterial cell (Bordet and Perkins 1970;Perkins and Nieto 1970;Nieto and Perkins 1971). Further, it was observed that vancomycin complexed with lipid II, and that peptidoglycan synthesis in Gaffkyia homari (which uses a distinct, tetrapeptidelinked precursor) was not inhibited (Hammes and Neuhaus 1974).…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Approved Glycopeptide Antibacterial Drugs: Mechanism of Action and Resistance

Zeng

Debabov

Hartsell³

et al. 2016

Cold Spring Harb Perspect Med

140

116

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The glycopeptide antimicrobials are a group of natural product and semisynthetic glycosylated peptides that show antibacterial activity against Gram-positive organisms through inhibition of cell-wall synthesis. This is achieved primarily through binding to the d-alanyl-d-alanine terminus of the lipid II bacterial cell-wall precursor, preventing cross-linking of the peptidoglycan layer. Vancomycin is the foundational member of the class, showing both clinical longevity and a still preferential role in the therapy of methicillin-resistant Staphylococcus aureus and of susceptible Enterococcus spp. Newer lipoglycopeptide derivatives (telavancin, dalbavancin, and oritavancin) were designed in a targeted fashion to increase antibacterial activity, in some cases through secondary mechanisms of action. Resistance to the glycopeptides emerged in delayed fashion and occurs via a spectrum of chromosome- and plasmid-associated elements that lead to structural alteration of the bacterial cell-wall precursor substrates.

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Iodinated vancomycin and mucopeptide biosynthesis by cell-free preparations from Micrococcus lysodeikticus

Cited by 16 publications

References 19 publications

Peptidoglycans synthesized by a membrane preparation of Micrococcus luteus

Peptidoglycans synthesized by a membrane preparation of Micrococcus luteus

Acceptor Specificity and Inhibition of the Bacterial Cell‐Wall Glycosyltransferase MurG

Approved Glycopeptide Antibacterial Drugs: Mechanism of Action and Resistance

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