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Antimicrobial Agents and Chemotherapy, April 2009, p. 1673-1678, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01340-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Mutations in Three Distinct Loci Cause Resistance to Peptide Deformylase Inhibitors in Bacillus subtilis{triangledown}

Yann Duroc, Carmela Giglione, and Thierry Meinnel*

Protein Maturation, Cell Fate and Therapeutics, ISV, UPR2355, Centre National de la Recherche Scientifique, Bât. 23A, 1 avenue de la Terrasse, F-91198 Gif-sur-Yvette Cedex, France

Received 7 October 2008/ Returned for modification 11 December 2008/ Accepted 20 January 2009

Bacillus subtilis mutants with resistance against peptide deformylase inhibitors were isolated. All showed a bypass of the pathway through mutations in three genes required for formylation of Met-tRNAfMet, fmt, folD, and glyA. glyA corresponds to a yet uncharacterized locus inducing resistance. The bypass of formylation caused robust fitness reduction but was not accompanied by alterations of the transcription profile. A subtle adaptation of the enzymes of the intermediary metabolism was observed.

* Corresponding author. Mailing address: Protein Maturation, Cell Fate and Therapeutics, ISV, UPR2355, Centre National de la Recherche Scientifique, Bât. 23A, 1 avenue de la Terrasse, F-91198 Gif-sur-Yvette Cedex, France. Phone: 33169823612. Fax: 33169823607. E-mail: thierry.meinnel{at}isv.cnrs-gif.fr

{triangledown} Published ahead of print on 26 January 2009.

Antimicrobial Agents and Chemotherapy, April 2009, p. 1673-1678, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01340-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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