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

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