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Mechanisms of Resistance

Resistance of Streptococcus pneumoniaeto Deformylase Inhibitors Is Due to Mutations indefB

Peter Margolis, Corinne Hackbarth, Sara Lopez, Mita Maniar, Wen Wang, Zhengyu Yuan, Richard White, Joaquim Trias
Peter Margolis
Versicor, Inc., Fremont, California 94555
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Corinne Hackbarth
Versicor, Inc., Fremont, California 94555
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Sara Lopez
Versicor, Inc., Fremont, California 94555
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Mita Maniar
Versicor, Inc., Fremont, California 94555
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Wen Wang
Versicor, Inc., Fremont, California 94555
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Zhengyu Yuan
Versicor, Inc., Fremont, California 94555
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Richard White
Versicor, Inc., Fremont, California 94555
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Joaquim Trias
Versicor, Inc., Fremont, California 94555
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DOI: 10.1128/AAC.45.9.2432-2435.2001
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ABSTRACT

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 adef paralog (defA) is not. Actinonin-resistant mutants of S. pneumoniae ATCC 49619 harbor mutations indefB but not in fmt. Reintroduction of the mutated defB gene into wild-type S. pneumoniaeR6x recreates the resistance phenotype. The altered enzyme displays decreased sensitivity to actinonin.

  • Copyright © 2001 American Society for Microbiology
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Resistance of Streptococcus pneumoniaeto Deformylase Inhibitors Is Due to Mutations indefB
Peter Margolis, Corinne Hackbarth, Sara Lopez, Mita Maniar, Wen Wang, Zhengyu Yuan, Richard White, Joaquim Trias
Antimicrobial Agents and Chemotherapy Sep 2001, 45 (9) 2432-2435; DOI: 10.1128/AAC.45.9.2432-2435.2001

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Resistance of Streptococcus pneumoniaeto Deformylase Inhibitors Is Due to Mutations indefB
Peter Margolis, Corinne Hackbarth, Sara Lopez, Mita Maniar, Wen Wang, Zhengyu Yuan, Richard White, Joaquim Trias
Antimicrobial Agents and Chemotherapy Sep 2001, 45 (9) 2432-2435; DOI: 10.1128/AAC.45.9.2432-2435.2001
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KEYWORDS

Amidohydrolases
Aminopeptidases
Anti-Bacterial Agents
Enzyme Inhibitors
Hydroxamic Acids
Streptococcus pneumoniae

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