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Antimicrobial Agents and Chemotherapy, September 2001, p. 2432-2435, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2432-2435.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Resistance of Streptococcus pneumoniae to Deformylase Inhibitors Is Due to Mutations in defB

Peter Margolis, Corinne Hackbarth, Sara Lopez, Mita Maniar, Wen Wang, Zhengyu Yuan, Richard White, and Joaquim Trias*

Versicor, Inc., Fremont, California 94555

Received 8 January 2001/Returned for modification 23 February 2001/Accepted 29 May 2001

Resistance to peptide deformylase inhibitors in Escherichia coli or Staphylococcus aureus is due to inactivation of transformylase activity. Knockout experiments in Streptococcus pneumoniae R6x indicate that the transformylase (fmt) and deformylase (defB) genes are essential and that a def paralog (defA) is not. Actinonin-resistant mutants of S. pneumoniae ATCC 49619 harbor mutations in defB but not in fmt. Reintroduction of the mutated defB gene into wild-type S. pneumoniae R6x recreates the resistance phenotype. The altered enzyme displays decreased sensitivity to actinonin.

* Corresponding author. Mailing address: Versicor, Inc., 34790 Ardentech Ct., Fremont, CA 94555. Phone: (510) 739-3025. Fax: (510) 739-3003. E-mail: jtrias{at}versicor.com.

Antimicrobial Agents and Chemotherapy, September 2001, p. 2432-2435, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2432-2435.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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