Lipid-Phosphoacetylmuramyl-Pentapeptide and Lipid-Phosphodisaccharide-Pentapeptide: Presumed Membrane Transport Intermediates in Cell Wall Synthesis

Anderson, John S.; Matsuhashi, Michio; Haskin, Mary A.; Strominger, Jack L.

doi:10.1073/pnas.53.4.881

Cited by 306 publications

(120 citation statements)

References 6 publications

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“…This confinns similar synergy studies of vancomycin plus cephalothin against MR S. epidermidis strains performed in this laboratory by a tube dilution checkerboard technique (13a). Vancomycin interferes with glycopeptide polymerization as a result of interference with the transfer of disaccharide-peptapeptide from a membrane lipid carrier to a cell wall acceptor in the second stage of cell wall synthesis (2,16). This occurs before the step of mucopeptide cross-linkage which is sensitive to the action of the cephalosporins (2).…”

Section: Resultsmentioning

confidence: 99%

Susceptibility and Synergy Studies of Methicillin-Resistant Staphylococcus epidermidis

Ein

Smith

Aruffo

et al. 1979

Antimicrob Agents Chemother

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Methicillin-resistant Staphylococcus epidermidis is an important cause of cerebrospinal fluid shunt infections and prosthetic valve endocarditis. Agar dilution miniimum inhibitory concentrations were determined for 100 strains of methicillin-resistant S. epidermidis which were isolated from clinical specimens. Vancomycin inhibited all 100 strains at s3.12 pug/ml, whereas clindamycin inhibited only 46 strains at <12.5 pg/mL. Methicillin-resistant S. epidermidis strains were resistant to achievable levels of erythromycin, with 90 strains having a minimum inhibitory concentration of 23.12 pg/ml. Of the five cephalosporins and one cephamycin tested, cefamandole was the most active in vitro, inhibiting 97 strains at S25 pug/ml. Antibiotic synergism was examined by a quantitative bacterial time-kill method. Synergism (.102 kill by the combination over the most effective single antibiotic at 24 h) was demonstrated with vancomycin (1.56 pLg/ml) plus cefamandole (6.25 pLg/ml) in 14 of 14 strains, vancomycin plus cephalothin (6.25 pLg/ml) in 14 of 14 strains, vancomycin plus rifampin (0.008 to 0.012 pg/ml) in 6 of 12 strains, rifampin plus cefamandole in 9 of 12 strains, and rifampin plus cephalothin in 10 of 12 strains. The emergence of populations of bacteria resistant to 0.2 pug of rifampin per ml developed in three offive methicillinresistant S. epidermidis strains tested. The addition of either vancomycin, cephalothin, or cefamandole to the rifampin prevented the emergence of resistance in these three strains. Clinical trials of synergistic antibiotic combination therapy for serious methicillin-resistant S. epidermidis infections are indicated.Staphylococcus epidermidis has been well established as a pathogen in the urinary tract (8), wounds (18), and, most importantly, infections involving indwelling artificial devices. S. epidermidis is the most common cause of prosthetic hip infections (10), cerebrospinal fluid shunt infections (1, 12), and prosthetic valve endocarditis (14, 15).The incidence of methicillin resistance in clinical isolates of S. epidermidis has ranged from 10% (11)

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Section: Resultsmentioning

confidence: 99%

Susceptibility and Synergy Studies of Methicillin-Resistant Staphylococcus epidermidis

Ein

Smith

Aruffo

et al. 1979

Antimicrob Agents Chemother

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“…1a) is a glycopeptide antibiotic that inhibits the final steps of peptidoglycan biosynthesis by binding to the D-Ala-D-Ala dipeptide termini of peptidoglycan precursors so that they cannot be further processed (1,2). The emergence of vancomycin resistance in the last decade has caused considerable concern because this drug is widely used to treat methicillin-resistant Gram-positive infections and there are few alternatives to it.…”

mentioning

confidence: 99%

Vancomycin analogues active against vanA-resistant strains inhibit bacterial transglycosylase without binding substrate

Chen

Walker

Sun

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

140

147

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Bacterial transglycosylases are enzymes that couple the disaccharide subunits of peptidoglycan to form long carbohydrate chains. These enzymes are the target of the pentasaccharide antibiotic moenomycin as well as the proposed target of certain glycopeptides that overcome vancomycin resistance. Because bacterial transglycosylases are difficult enzymes to study, it has not previously been possible to evaluate how moenomycin inhibits them or to determine whether glycopeptide analogues directly target them. We have identified transglycosylase assay conditions that enable kinetic analysis of inhibitors and have examined the inhibition of Escherichia coli penicillin-binding protein 1b (PBP1b) by moenomycin as well as by various glycopeptides. We report that chlorobiphenyl vancomycin analogues that are incapable of binding substrates nevertheless inhibit E. coli PBP1b, which shows that these compounds interact directly with the enzyme. These findings support the hypothesis that chlorobiphenyl vancomycin derivatives overcome vanA resistance by targeting bacterial transglycosylases. We have also found that moenomycin is not competitive with respect to the lipid II substrate of PBP1b, as has long been believed. With the development of suitable methods to evaluate bacterial transglycosylases, it is now possible to probe the mechanism of action of some potentially very important antibiotics.

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“…These short peptide bridges are synthesized in a non-ribosome catalyzed peptidyl transferase reaction, which uses the charged glycyl-tRNA, 1 np-tRNA Gly and a ‘pseudo’-tRNA Gly UCC as substrates. 65,85,92 Glycine and serine act as substrates that are successively added to form small peptide bridges which are catalyzed by a family of non-ribosomal peptidyl transferases known as FEM-XAB (Factors Essential for Methicillin Resistance) - mediated cell wall synthesis. 93 The incomplete formation of these interpeptide bridges can lead to increased antibiotic susceptibility or lethality.…”

Section: Unmodified Wobble Position 34 and The Importance Of Position 32mentioning

confidence: 99%

Celebrating wobble decoding: Half a century and still much is new

et al. 2017

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A simple post-transcriptional modification of tRNA, deamination of adenosine to inosine at the first, or wobble, position of the anticodon, inspired Francis Crick's Wobble Hypothesis 50 years ago. Many more naturally-occurring modifications have been elucidated and continue to be discovered. The post-transcriptional modifications of tRNA's anticodon domain are the most diverse and chemically complex of any RNA modifications. Their contribution with regards to chemistry, structure and dynamics reveal individual and combined effects on tRNA function in recognition of cognate and wobble codons. As forecast by the Modified Wobble Hypothesis 25 years ago, some individual modifications at tRNA's wobble position have evolved to restrict codon recognition whereas others expand the tRNA's ability to read as many as four synonymous codons. Here, we review tRNA wobble codon recognition using specific examples of simple and complex modification chemistries that alter tRNA function. Understanding natural modifications has inspired evolutionary insights and possible innovation in protein synthesis.

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Lipid-Phosphoacetylmuramyl-Pentapeptide and Lipid-Phosphodisaccharide-Pentapeptide: Presumed Membrane Transport Intermediates in Cell Wall Synthesis

Cited by 306 publications

References 6 publications

Susceptibility and Synergy Studies of Methicillin-Resistant Staphylococcus epidermidis

Susceptibility and Synergy Studies of Methicillin-Resistant Staphylococcus epidermidis

Vancomycin analogues active against vanA-resistant strains inhibit bacterial transglycosylase without binding substrate

Celebrating wobble decoding: Half a century and still much is new

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