Peptide Deformylase (def) is essential in Mycobacterium smegmatis, but the essentiality is compensated by inactivation of methionine formylation

Abstract

AbstractBackgroundCo-translational processes in bacteria are attractive drug targets, but while some processes are essential, others are not. The essentiality of Peptide Deformylase (PDF,def) for vitality of mycobacteria was speculated, but never unequivocally proven.ResultsHere we show by targeted deletion experiments thatdefcan only be deleted fromM. smegmatiswhen an additional copy is present; that prior deletion of tRNAfMet-Formyl Transferase (FMT, encoded byfmt) rendersdefcompletely dispensable; and that re-introduction offmtinto aΔdefmutant is not possible – constituting a definitive proof for the essentiality ofdefin mycobacteria.ConclusionsPeptide deformylase is essential inM. smegmatis, but the fact that inactivation offmtrenders the gene completely dispensable, and thus any inhibitor ofdefuseless, casts doubt on the usefulness of PDF as a drug-target in mycobacteria.