The <i>vanG</i> glycopeptide resistance operon from <i>Enterococcus faecalis</i> revisited

Depardieu, Florence; Bonora, Maria; Reynolds, Peter E.; Courvalin, Patrice

doi:10.1046/j.1365-2958.2003.03737.x

Cited by 147 publications

(143 citation statements)

References 60 publications

(110 reference statements)

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“…The vanG-like transcription was also analysed in mid-exponential growth phase in the presence of teicoplanin (1/4 MIC) but no induction was observed (data not shown). These data are consistent with the VanG phenotype, which confers low-level resistance to vancomycin but no resistance to teicoplanin in E. faecalis (Depardieu et al, 2003).…”

Section: Transcriptional Analysis Of the Vang-like Gene Clustersupporting

confidence: 86%

“…1.5 kb was obtained (Fig. 1c), indicating that the vanG-like, vanXY G -like and vanT G -like genes are co-transcribed in a unique polycistronic mRNA, similarly to the vanG operons of E. faecalis (Depardieu et al, 2003).…”

Section: Resultsmentioning

confidence: 88%

“…Two distinct vanG operons, vanG1 and vanG2, have been described in E. faecalis (Boyd et al, 2006;Depardieu et al, 2003;McKessar et al, 2000). The VanG phenotype corresponds to low-level resistance to vancomycin and susceptibility to teicoplanin.…”

Section: Introductionmentioning

confidence: 99%

“…The VanG phenotype corresponds to low-level resistance to vancomycin and susceptibility to teicoplanin. This resistance results from the acquisition of an operonic cluster of genes consisting in vanG1 of three regulatory genes (vanU G , vanR G , vanS G ) and five effector genes (vanY G , vanW G , vanG, vanXY G , vanT G ) transcribed from two distinct promoters (Depardieu et al, 2003). The vanG2 operon harbours the same genetic organization but lacks the vanY G gene.…”

Section: Introductionmentioning

confidence: 99%

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Genomic and expression analysis of the vanG-like gene cluster of Clostridium difficile

et al. 2013

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Primary antibiotic treatment of Clostridium difficile intestinal diseases requires metronidazole or vancomycin therapy. A cluster of genes homologous to enterococcal glycopeptides resistance vanG genes was found in the genome of C. difficile 630, although this strain remains sensitive to vancomycin. This vanG-like gene cluster was found to consist of five ORFs: the regulatory region consisting of vanR and vanS and the effector region consisting of vanG, vanXY and vanT. We found that 57 out of 83 C. difficile strains, representative of the main lineages of the species, harbour this vanG-like cluster. The cluster is expressed as an operon and, when present, is found at the same genomic location in all strains. The vanG, vanXY and vanT homologues in C. difficile 630 are co-transcribed and expressed to a low level throughout the growth phases in the absence of vancomycin. Conversely, the expression of these genes is strongly induced in the presence of subinhibitory concentrations of vancomycin, indicating that the vanG-like operon is functional at the transcriptional level in C. difficile. Hydrophilic interaction liquid chromatography (HILIC-HPLC) and MS analysis of cytoplasmic peptidoglycan precursors of C. difficile 630 grown without vancomycin revealed the exclusive presence of a UDP-MurNAc-pentapeptide with an alanine at the C terminus. UDP-MurNAc-pentapeptide [D-Ala] was also the only peptidoglycan precursor detected in C. difficile grown in the presence of vancomycin, corroborating the lack of vancomycin resistance. Peptidoglycan structures of a vanG-like mutant strain and of a strain lacking the vanG-like cluster did not differ from the C. difficile 630 strain, indicating that the vanGlike cluster also has no impact on cell-wall composition.

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Section: Transcriptional Analysis Of the Vang-like Gene Clustersupporting

confidence: 86%

Section: Resultsmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genomic and expression analysis of the vanG-like gene cluster of Clostridium difficile

et al. 2013

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“…The VanXY C enzyme is selective against resistant dipeptide and pentapeptide peptidoglycan substrates ending in D-Ser (8). Finally, the VanXY G enzyme, first assigned as a dual substrate active "XY" enzyme by sequence similarity (11), was later shown to lack D,D-pentapeptidase activity typical for bona fide VanXY enzymes (12). The molecular determinants responsible for such diversity of substrate specificity among Van D,D-peptidases are unknown, limiting the understanding of their evolution and hampering the development of inhibitors that could be used in combination with glycopeptides.…”

mentioning

confidence: 99%

Structural basis for the evolution of vancomycin resistance D , D -peptidases

Meziane‐Cherif

Stogios

Evdokimova

et al. 2014

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

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VanXY residues 110-115 form a mobile cap over the catalytic site, whose flexibility is involved in the switch between di-and pentapeptide hydrolysis. Structure-based alignment of the Van D,D-peptidases showed that VanY enzymes lack this element, which promotes binding of the penta-rather than that of the dipeptide. The structures also highlight the molecular basis for selection of D-Ala-ending precursors over the modified resistance targets. These results illustrate the remarkable adaptability of the D,D-peptidase fold in response to antibiotic pressure via evolution of specific structural elements that confer hydrolytic activity against vancomycin-susceptible peptidoglycan precursors.antibiotic resistance | glycopeptides | enzyme evolution | metallopeptidases | subfamily M15BT he emergence of high-level resistance to vancomycin, a last resort antibiotic against Gram-positive bacteria, in Enterococcus spp. and its spread to methicillin-resistant Staphylococcus aureus is a serious threat to public health (1). Vancomycin acts by binding to the D-alanyl-D-alanine moiety of the uncross-linked SignificanceVancomycin is a powerful antibiotic against Gram-positive bacteria that inhibits cell-wall synthesis by binding with high affinity to peptidoglycan precursors. Resistance to vancomycin is due to acquisition of operons encoding, among other enzymes, the zinc-dependent D,D-peptidases VanX, VanY, or VanXY, which catalyze the removal of the drug targets. Structural characterization of VanXY elucidates the molecular basis of their specificity toward vancomycin-susceptible precursors and explains the dual function of VanXY. These studies highlight the striking plasticity of peptidoglycan-modifying enzymes to evolve to antibiotic resistance proteins. They also provide the molecular framework for development of D,D-peptidase inhibitors that may help to curb vancomycin resistance.Author contributions: D.M.-C., P.J.S., A.S., and P.C. designed research; D.M.-C., P.J.S., and E.E. performed research; D.M.-C., P.J.S., A.S., and P.C. analyzed data; and D.M.-C., P.J.S., A.S., and P.C. wrote the paper.The authors declare no conflict of interest. *This Direct Submission article had a prearranged editor.Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 4F78, 4MUQ-4MUT, and 4OAK).

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A review on comparative mechanistic studies of antimicrobial peptides against archaea

Varnava

Ronimus

Sarojini

2017

Biotech & Bioengineering

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Archaea was until recently considered as a third domain of life in addition to bacteria and eukarya but recent studies support the existence of only two superphyla (bacteria and archaea). The fundamental differences between archaeal, bacterial, and eukaryal cells are probably the main reasons for the comparatively lower susceptibility of archaeal strains to current antimicrobial agents. The possible emerging pathogenicity of archaea and the role of archaeal methanogens in methane emissions, a potent greenhouse gas, has led many researchers to examine the sensitivity patterns of archaea and make attempts to find agents that have significant anti-archaeal activity. Even though antimicrobial peptides (AMPs) are well known with several published reviews concerning their mode of action against bacteria and eukarya, to our knowledge, to date no reviews are available that focus on the action of these peptides against archaea. Herein, we present a review on all the peptides that have been tested against archaea. In addition, in an attempt to shed more light on possible future work that needs to be performed we have included a brief overview of the chemical characteristics, spectrum of activity, and the known mechanism of action of each of these peptides against bacteria and/or fungi. We also discuss the nature of and key physiological differences between Archaea, Bacteria, and Eukarya that are relevant to the development of anti-archaeal peptides. Despite our relatively limited knowledge about archaea, available data suggest that AMPs have an even broader spectrum of activity than currently recognized.

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The vanG glycopeptide resistance operon from Enterococcus faecalis revisited

Cited by 147 publications

References 60 publications

Genomic and expression analysis of the vanG-like gene cluster of Clostridium difficile

Genomic and expression analysis of the vanG-like gene cluster of Clostridium difficile

Structural basis for the evolution of vancomycin resistance D , D -peptidases

A review on comparative mechanistic studies of antimicrobial peptides against archaea

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