Oritavancin Retains a High Affinity for a Vancomycin-Resistant Cell-Wall Precursor via Its Bivalent Motifs of Interaction

Biochemistry ◽  
2018 ◽  
Vol 57 (18) ◽  
pp. 2723-2732 ◽  
Author(s):  
Sierra Bowden ◽  
Christine Joseph ◽  
Shengzhuang Tang ◽  
Jayme Cannon ◽  
Emily Francis ◽  
...  
Keyword(s):  
Cell Wall ◽  
Resistant Cell ◽  
High Affinity ◽  
Vancomycin Resistant

scholarly journals The Craterostigma plantagineum protein kinase CpWAK1 interacts with pectin and integrates different environmental signals in the cell wall

Planta ◽  
2021 ◽  
Vol 253 (5) ◽  
Author(s):  
Peilei Chen ◽  
Valentino Giarola ◽  
Dorothea Bartels
Keyword(s):  
Cell Wall ◽  
Stress Responses ◽  
Expression Profiles ◽  
Phylogenetic Analyses ◽  
Cell Wall Protein ◽  
Biological Processes ◽  
Environmental Signals ◽  
High Affinity ◽  
Craterostigma Plantagineum ◽  
Receptor Kinases

Abstract Main conclusion The cell wall protein CpWAK1 interacts with pectin, participates in decoding cell wall signals, and induces different downstream responses. Abstract Cell wall-associated protein kinases (WAKs) are transmembrane receptor kinases. In the desiccation-tolerant resurrection plant Craterostigma plantagineum, CpWAK1 has been shown to be involved in stress responses and cell expansion by forming a complex with the C. plantagineum glycine-rich protein1 (CpGRP1). This prompted us to extend the studies of WAK genes in C. plantagineum. The phylogenetic analyses of WAKs from C. plantagineum and from other species suggest that these genes have been duplicated after species divergence. Expression profiles indicate that CpWAKs are involved in various biological processes, including dehydration-induced responses and SA- and JA-related reactions to pathogens and wounding. CpWAK1 shows a high affinity for “egg-box” pectin structures. ELISA assays revealed that the binding of CpWAKs to pectins is modulated by CpGRP1 and it depends on the apoplastic pH. The formation of CpWAK multimers is the prerequisite for the CpWAK–pectin binding. Different pectin extracts lead to opposite trends of CpWAK–pectin binding in the presence of Ca2+ at pH 8. These observations demonstrate that CpWAKs can potentially discriminate and integrate cell wall signals generated by diverse stimuli, in concert with other elements, such as CpGRP1, pHapo, Ca2+[apo], and via the formation of CpWAK multimers.

Relationships between algal coals and resistant cell wall biopolymers of extant algae as revealed by Py-GC-MS

1988 ◽  
Vol 20 ◽  
pp. 93-101 ◽  
Author(s):  
S. Derenne ◽  
C. Largeau ◽  
E. Casadevall ◽  
E. Tegelaar ◽  
J.W. De Leeuw
Keyword(s):  
Cell Wall ◽  
Resistant Cell

scholarly journals Rapid in vivo development of resistance to daptomycin in vancomycin-resistant Enterococcus faecium due to genomic rearrangements

2021 ◽  
Author(s):  
Sarah Mollerup ◽  
Christine Elmeskov ◽  
Heidi Gumpert ◽  
Mette Pinholt ◽  
Tobias Steen Sejersen ◽  
...  
Keyword(s):  
Cell Wall ◽  
Enterococcus Faecium ◽  
Chromosomal Rearrangements ◽  
Resistance Mechanisms ◽  
Resistant Isolate ◽  
Wall Structure ◽  
Whole Genome ◽  
Cyclic Lipopeptide ◽  
Vancomycin Resistant

AbstractBackgroundDaptomycin is a cyclic lipopeptide used in the treatment of vancomycin-resistant Enterococcus faecium (VREfm). However, the development of daptomycin-resistant VREfm challenges the treatment of nosocomial VREfm infections. Resistance mechanisms of daptomycin are not fully understood. Here we analysed the genomic changes leading to a daptomycin-susceptible VREfm isolate becoming resistant after 40 days of daptomycin and linezolid combination therapy.MethodsThe two isogenic VREfm isolates (daptomycin-susceptible and daptomycin-resistant) were analysed using whole genome sequencing with Illumina and Nanopore.ResultsWhole genome comparative analysis identified the loss of a 46.5 kb fragment and duplication of a 29.7 kb fragment in the daptomycin-resistant isolate, with many implicated genes involved in cell wall synthesis. Two plasmids of the daptomycin-susceptible isolate were also found integrated in the chromosome of the resistant isolate. One nonsynonymous SNP in the rpoC gene was identified in the daptomycin-resistant isolate.ConclusionsDaptomycin resistance developed through chromosomal rearrangements leading to altered cell wall structure. Such novel types of resistance mechanisms can only be identified by comparing closed genomes of isogenic isolates.

scholarly journals Interactions between Penicillin-Binding Proteins (PBPs) and Two Novel Classes of PBP Inhibitors, Arylalkylidene Rhodanines and Arylalkylidene Iminothiazolidin-4-ones

2004 ◽  
Vol 48 (3) ◽  
pp. 961-969 ◽  
Author(s):  
Astrid Zervosen ◽  
Wei-Ping Lu ◽  
Zhouliang Chen ◽  
Ronald E. White ◽  
Thomas P. Demuth ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Wall ◽  
Cell Wall Synthesis ◽  
Bacterial Strains ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
E Coli ◽  
Peptidoglycan Biosynthesis ◽  
Vancomycin Resistant ◽  
Inhibitory Activities

ABSTRACT Several non-β-lactam compounds were active against various gram-positive and gram-negative bacterial strains. The MICs of arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-ones were lower than those of ampicillin and cefotaxime for methicillin-resistant Staphylococcus aureus MI339 and vancomycin-resistant Enterococcus faecium EF12. Several compounds were found to inhibit the cell wall synthesis of S. aureus and the last two steps of peptidoglycan biosynthesis catalyzed by ether-treated cells of Escherichia coli or cell wall membrane preparations of Bacillus megaterium. The effects of the arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-one derivatives on E. coli PBP 3 and PBP 5, Streptococcus pneumoniae PBP 2xS (PBP 2x from a penicillin-sensitive strain) and PBP 2xR (PBP 2x from a penicillin-resistant strain), low-affinity PBP 2a of S. aureus, and the Actinomadura sp. strain R39 and Streptomyces sp. strain R61 dd-peptidases were studied. Some of the compounds exhibited inhibitory activities in the 10 to 100 μM concentration range. The inhibition of PBP 2xS by several of them appeared to be noncompetitive. The dissociation constant for the best inhibitor (Ki = 10 μM) was not influenced by the presence of the substrate.

scholarly journals Penicillin-Binding Protein 2 Is Essential for Expression of High-Level Vancomycin Resistance and Cell Wall Synthesis in Vancomycin- Resistant Staphylococcus aureus Carrying the Enterococcal vanA Gene Complex

2004 ◽  
Vol 48 (12) ◽  
pp. 4566-4573 ◽  
Author(s):  
Anatoly Severin ◽  
Shang Wei Wu ◽  
Keiko Tabei ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Binding Protein ◽  
Inducible Promoter ◽  
Protein Product ◽  
Vancomycin Resistance ◽  
Penicillin Binding Protein ◽  
Oxacillin Resistance ◽  
Vancomycin Resistant ◽  
High Level

ABSTRACT A combination of biochemical and genetic experiments were performed in order to better understand the mechanism of expression of high-level vancomycin resistance in Staphylococcus aureus. The transcription of pbp2 of the highly vancomycin- and oxacillin-resistant strain COLVA200 and its mutant derivative with inactivated mecA were put under the control of an inducible promoter, and the dependence of oxacillin and vancomycin resistance and cell wall composition on the concentration of the isopropyl-β-d-thiogalactopyranoside inducer was determined. The results indicate that mecA—the genetic determinant of oxacillin resistance—while essential for oxacillin resistance, is not involved with the expression of vancomycin resistance. Penicillin binding protein 2A, the protein product of mecA, appears to be unable to utilize the depsipeptide cell wall precursor produced in the vancomycin-resistant cells for transpeptidation. The key penicillin binding protein essential for vancomycin resistance and for the synthesis of the abnormally structured cell walls characteristic of vancomycin-resistant S. aureus (A. Severin, K. Tabei, F. Tenover, M. Chung, N. Clarke, and A. Tomasz, J. Biol. Chem. 279:3398-3407, 2004) is penicillin binding protein 2.

scholarly journals Substrate Inhibition of VanA by d-Alanine Reduces Vancomycin Resistance in a VanX-Dependent Manner

2016 ◽  
Vol 60 (8) ◽  
pp. 4930-4939 ◽  
Author(s):  
Lizah T. van der Aart ◽  
Nicole Lemmens ◽  
Willem J. van Wamel ◽  
Gilles P. van Wezel
Keyword(s):  
Cell Wall ◽  
Streptomyces Coelicolor ◽  
Substrate Inhibition ◽  
Model Organism ◽  
Vancomycin Resistance ◽  
Dependent Manner ◽  
Wild Type ◽  
Content Type ◽  
Lipid Ii ◽  
Vancomycin Resistant

ABSTRACTThe increasing resistance of clinical pathogens against the glycopeptide antibiotic vancomycin, a last-resort drug against infections with Gram-positive pathogens, is a major problem in the nosocomial environment. Vancomycin inhibits peptidoglycan synthesis by binding to thed-Ala–d-Ala terminal dipeptide moiety of the cell wall precursor lipid II. Plasmid-transferable resistance is conferred by modification of the terminal dipeptide into the vancomycin-insensitive variantd-Ala–d-Lac, which is produced by VanA. Here we show that exogenousd-Ala competes withd-Lac as a substrate for VanA, increasing the ratio of wild-type to mutant dipeptide, an effect that was augmented by several orders of magnitude in the absence of thed-Ala–d-Ala peptidase VanX. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that high concentrations ofd-Ala led to the production of a significant amount of wild-type cell wall precursors, whilevanX-null mutants produced primarily wild-type precursors. This enhanced the efficacy of vancomycin in the vancomycin-resistant model organismStreptomyces coelicolor, and the susceptibility of vancomycin-resistant clinical isolates ofEnterococcus faecium(VRE) increased by up to 100-fold. The enhanced vancomycin sensitivity ofS. coelicolorcells correlated directly to increased binding of the antibiotic to the cell wall. Our work offers new perspectives for the treatment of diseases associated with vancomycin-resistant pathogens and for the development of drugs that target vancomycin resistance.

scholarly journals Clinical Isolate of Vancomycin-HeterointermediateStaphylococcus aureus Susceptible to Methicillin and In Vitro Selection of a Vancomycin-Resistant Derivative

2001 ◽  
Vol 45 (1) ◽  
pp. 349-352 ◽  
Author(s):  
Sophie Bobin-Dubreux ◽  
Marie-Elisabeth Reverdy ◽  
Chantal Nervi ◽  
Martine Rougier ◽  
Anne Bolmström ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Clinical Isolate ◽  
Electron Micrographs ◽  
Parent Strain ◽  
In Vitro Selection ◽  
Glycopeptide Antibiotics ◽  
Vancomycin Resistant ◽  
Selection Of

ABSTRACT A Staphylococcus aureus strain with low-level heteroresistance to vancomycin (designated MER) but susceptible to methicillin was isolated from an outpatient with conjunctivitis who did not receive any glycopeptide antibiotics. Incubation of the parent strain, MER, with increasing concentrations of vancomycin led to rapid selection of a stable progeny homogeneously resistant to vancomycin. Electron micrographs of strain MER showed enhanced cell wall thickness and abnormal septations typically seen with methicillin-resistantS. aureus having intermediate susceptibility to vancomycin.

scholarly journals Katanosin B and Plusbacin A3, Inhibitors of Peptidoglycan Synthesis in Methicillin-ResistantStaphylococcus aureus

2001 ◽  
Vol 45 (6) ◽  
pp. 1823-1827 ◽  
Author(s):  
Hideki Maki ◽  
Kenji Miura ◽  
Yoshinori Yamano
Keyword(s):  
Cell Wall ◽  
Antibacterial Activity ◽  
Whole Cells ◽  
Gram Positive Bacteria ◽  
Peptidoglycan Synthesis ◽  
Cyclic Depsipeptide ◽  
Naturally Occurring ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

ABSTRACT Both katanosin B and plusbacin A3 are naturally occurring cyclic depsipeptide antibiotics containing a lactone linkage. They showed strong antibacterial activity against methicillin-resistantStaphylococcus aureus and VanA-type vancomycin-resistant enterococci, with MICs ranging from 0.39 to 3.13 μg/ml, as well as against other gram-positive bacteria. They inhibited the incorporation of N-acetylglucosamine, a precursor of cell wall synthesis, into peptidoglycan of S. aureus whole cells at concentrations close to their MICs. In vitro studies with a wall-membrane particulate fraction of S. aureus showed that katanosin B and plusbacin A3 inhibited the formation of lipid intermediates, with 50% inhibitory concentrations (IC50s) of 2.2 and 2.3 μg/ml, respectively, and inhibited the formation of nascent peptidoglycan, with IC50s of 0.8 and 0.4 μg/ml, respectively. Vancomycin, a well-known inhibitor of transglycosylation, did not inhibit the formation of lipid intermediates but did inhibit the formation of nascent peptidoglycan, with an IC50 of 4.1 μg/ml. Acetyl-Lys-d-Ala-d-Ala, an analog of the terminus of the lipid intermediates, effectively suppressed the inhibition of transglycosylation by vancomycin, but did not suppress those by katanosin B and plusbacin A3. These results indicate that the antibacterial activity of katanosin B and plusbacin A3 is due to blocking of transglycosylation and its foregoing steps of cell wall peptidoglycan synthesis via a mechanism differing from that of vancomycin.

scholarly journals Gradual Alterations in Cell Wall Structure and Metabolism in Vancomycin-Resistant Mutants ofStaphylococcus aureus

1999 ◽  
Vol 181 (24) ◽  
pp. 7566-7570 ◽  
Author(s):  
Krzysztof Sieradzki ◽  
Alexander Tomasz
Keyword(s):  
Cell Wall ◽  
Methicillin Resistance ◽  
Specific Inhibitor ◽  
Wall Structure ◽  
Penicillin Binding Protein ◽  
Cell Wall Metabolism ◽  
Gradual Reduction ◽  
Vancomycin Resistant ◽  
Resistant Mutants ◽  
Structure And Metabolism

ABSTRACT In five vancomycin-resistant laboratory step mutants selected from the highly and homogeneously methicillin-resistant Staphylococcus aureus strain COL (MIC of methicillin, 800 μg/ml; MIC of vancomycin, 1.5 μg/ml), the gradually increasing levels of resistance to vancomycin were accompanied by parallel decreases in the levels of methicillin resistance and abnormalities in cell wall metabolism. The latter included a gradual reduction in the proportion of highly cross-linked muropeptide species in peptidoglycan, down-regulation of the production of penicillin-binding protein 2A (PBP2A) and PBP4, and hypersensitivity to β-lactam antibiotics each with a relatively selective affinity for the various staphylococcal PBPs; the PBP2-specific inhibitor ceftizoxime was particularly effective.

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