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. 2001 Sep;45(9):2432-5.
doi: 10.1128/AAC.45.9.2432-2435.2001.

Resistance of Streptococcus pneumoniae to deformylase inhibitors is due to mutations in defB

P Margolis  1 , C Hackbarth, S Lopez, M Maniar, W Wang, Z Yuan, R White, J Trias
Affiliations

Resistance of Streptococcus pneumoniae to deformylase inhibitors is due to mutations in defB

P Margolis et al. Antimicrob Agents Chemother. 2001 Sep.

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 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.

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Figures

FIG. 1
FIG. 1
Alignment of conserved domains of deformylase proteins. Partial sequences of the predicted products of the defA and defB homologs of S. aureus and S. pneumoniae are shown aligned with consensus PDF domains (13). Residues that diverge from the consensus are highlighted. Modifications in the deformylase enzyme in the resistant S. pneumoniae mutants VSPN6501, VSPN6503, and VSPN6504 are indicated by arrows. The positions of the motifs in the S. pneumoniae DefB are as follows: box 1, G69 to Q76; box 2, A123 to S132; and box 3, Q172 to G182. The sequences of the S. pneumoniae def homologs from strain R6x have been submitted to GenBank (accession numbers: defA, AY014508; defB, AY014509). Sequences of the S. pneumoniae def and fmt homologs from S. pneumoniae ATCC 49619 were also submitted to GenBank (accession numbers: defA, AY014510; defB, AY014511; fmt, AY014512).
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