This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Beltrametti, F.
Right arrow Articles by Marinelli, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Beltrametti, F.
Right arrow Articles by Marinelli, F.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2007, p. 1135-1141, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01071-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Resistance to Glycopeptide Antibiotics in the Teicoplanin Producer Is Mediated by van Gene Homologue Expression Directing the Synthesis of a Modified Cell Wall Peptidoglycan{triangledown}

Fabrizio Beltrametti,1* Arianna Consolandi,1 Lucia Carrano,1 Francesca Bagatin,1 Roberta Rossi,1 Livia Leoni,2 Elisabetta Zennaro,2 Enrico Selva,1 and Flavia Marinelli1,3

Vicuron Pharmaceuticals, Via R. Lepetit, 34, 21040, Gerenzano (Varese) Italy,1 Dipartimento di Biologia, Università degli Studi di Roma Tre, Viale Marconi 446, 00164 Rome, Italy,2 Dipartimento di Biotecnologie e Scienze Molecolari, Università degli Studi dell'Insubria, Via J. H. Dunant 3, 21100 Varese, Italy3

Received 25 August 2006/ Returned for modification 18 October 2006/ Accepted 31 December 2006

Glycopeptide resistance has been studied in detail in enterococci and staphylococci. In these microorganisms, high-level resistance is achieved by replacing the C-terminal D-alanyl-D-alanine of the nascent peptidoglycan with D-alanyl-D-lactate or D-alanyl-D-serine, thus reducing the affinities of glycopeptides for cell wall targets. Reorganization of the cell wall is directed by the expression of the van gene clusters. The identification of van gene homologs in the genomes of several glycopeptide-producing actinomycetes suggests the involvement of a similar self-resistance mechanism to avoid suicide. This report describes a comprehensive study of self-resistance in Actinoplanes teichomyceticus ATCC 31121, the producer of the clinically relevant glycopeptide teicoplanin. A. teichomyceticus ATCC 31121 showed a MIC of teicoplanin of 25 µg/ml and a MIC of vancomycin of 90 µg/ml during vegetative growth. The vanH, vanA, and vanX genes of A. teichomyceticus were found to be organized in an operon whose transcription was constitutive. Analysis of the UDP-linked peptidoglycan precursors revealed the presence of UDP-glycomuramyl pentadepsipeptide terminating in D-alanyl-D-lactate. No trace of precursors ending in D-alanyl-D-alanine was detected. Thus, the van gene complex was transcribed and expressed in the genetic background of A. teichomyceticus and conferred resistance to vancomycin and teicoplanin through the modification of cell wall biosynthesis. During teicoplanin production (maximum productivity, 70 to 80 µg/ml), the MIC of teicoplanin remained in the range of 25 to 35 µg/ml. Teicoplanin-producing cells were found to be tolerant to high concentrations of exogenously added glycopeptides, which were not bactericidal even at 5,000 µg/ml.

* Corresponding author. Mailing address: Vicuron Pharmaceuticals, Via R. Lepetit, 34, 21040 Gerenzano (VA), Italy. Phone: 39 02 96474404. Fax: 39 02 96474238. E-mail: fbeltrametti{at}vicuron.it

{triangledown} Published ahead of print on 12 January 2007.

Antimicrobial Agents and Chemotherapy, April 2007, p. 1135-1141, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01071-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hawkey, P. M. (2008). The growing burden of antimicrobial resistance. J Antimicrob Chemother 62: i1-i9 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»