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VanB-type Enterococcus faecium clinical isolate successively inducibly resistant to, dependent on, and constitutively resistant to vancomycin

Antimicrobial Agents and Chemotherapy publish this investigation article

May 1st, 2009

Three Enterococcus faecium strains isolated successively from the same patient, vancomycin-resistant strain BM4659, vancomycin-dependent strain BM4660, and vancomycin-revertant strain BM4661, were indistinguishable by pulsed-field gel electrophoresis and harbored plasmid pIP846, which confers VanB-type resistance. The vancomycin dependence of strain BM4660 was due to mutation P(175)L, which suppressed the activity of the host Ddl D-Ala:D-Ala ligase. Reversion to resistance in strain BM4661 was due to a G-to-C transversion in the transcription terminator of the vanRS(B) operon that lowered the free energy of pairing from -13.08 to -6.65 kcal/mol, leading to low-level constitutive expression of the resistance genes from the P(RB) promoter, as indicated by analysis of peptidoglycan precursors and of VanX(B) D,D-dipeptidase activity. Transcription of the resistance genes, studied by Northern hybridization and reverse transcription, initiated from the P(YB) resistance promoter, was inducible in strains BM4659 and BM4660, whereas it started from the P(RB) regulatory promoter in strain BM4661, where it was superinducible. Strain BM4661 provides the first example of reversion to vancomycin resistance of a VanB-type dependent strain not due to a compensatory mutation in the ddl or vanS(B) gene. Instead, a mutation in the transcription terminator of the regulatory genes resulted in transcriptional readthrough of the resistance genes from the P(RB) promoter in the absence of vancomycin




San Millan A., Depardieu F., Godreuil S. and Courvalin P.




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VanB-type Enterococcus faecium clinical isolate successively inducibly resistant to, dependent on, and constitutively resistant to vancomycin

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VanB-type Enterococcus faecium clinical isolate successively inducibly resistant to, dependent on, and constitutively resistant to vancomycin



Participants:

Universidad ComplutenseServicio de Zoonosis de Transmisión Alimentaria y Resistencia a Antimicrobianos (ZTA). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).

Institut PasteurInstitut Pasteur.

Université de MontpellierLaboratoire de Bactériologie. Hôpital Universitaire Arnaud de Villeneuve. Université de Montpellier (UM1).







Antimicrobial Agents and Chemotherapy
FACTOR YEAR Q
4.802 2009

NLMID: 315061

PMID: 19273676

ISSN: 0066-4804



TITLE: VanB-type Enterococcus faecium clinical isolate successively inducibly resistant to, dependent on, and constitutively resistant to vancomycin


JOURNAL: Antimicrob Agents Chemother


NUMERACIÓN: 53(5):1974-82


AÑO: 2009


PUBLISHER: American Society for Microbiology


AUTHORS: San Millan A., Depardieu F., Godreuil S. and Courvalin P.


DOI: https://doi.org/10.1128/AAC.00034-09


CITE THIS PUBLICATION:

San Millan A., Depardieu F., Godreuil S. and Courvalin P. VanB-type Enterococcus faecium clinical isolate successively inducibly resistant to, dependent on, and constitutively resistant to vancomycin. Antimicrobial Agents and Chemotherapy. 53(5):1974-82. 2009. (A). ISSN: 0066-4804. DOI: 10.1128/AAC.00034-09


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