Peptide Deformylase (def) is essential in Mycobacterium smegmatis, but the essentiality is compensated by inactivation of methionine formylation
Abstract Background Co-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. Results Here we show by targ...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-10-01
|
| Series: | BMC Microbiology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12866-019-1611-7 |
| _version_ | 1819063463428751360 |
|---|---|
| author | Noga Naor Omer Gadot Michal Meir Daniel Barkan |
| author_facet | Noga Naor Omer Gadot Michal Meir Daniel Barkan |
| author_sort | Noga Naor |
| collection | DOAJ |
| description | Abstract Background Co-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. Results Here we show by targeted deletion experiments that def can only be deleted from M. smegmatis when an additional copy is present; that prior deletion of tRNAfMet-Formyl Transferase (FMT, encoded by fmt) renders def completely dispensable; and that re-introduction of fmt into a Δdef mutant is not possible – constituting a definitive proof for the essentiality of def in mycobacteria. Conclusions Peptide deformylase is essential in M. smegmatis, but the fact that inactivation of fmt renders the gene completely dispensable, and thus any inhibitor of def useless, casts doubt on the usefulness of PDF as a drug-target in mycobacteria. |
| first_indexed | 2024-12-21T15:15:04Z |
| format | Article |
| id | doaj.art-0ccf1d7794be4d85ad30503871bbec33 |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-12-21T15:15:04Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Microbiology |
| spelling | doaj.art-0ccf1d7794be4d85ad30503871bbec332022-12-21T18:59:11ZengBMCBMC Microbiology1471-21802019-10-011911610.1186/s12866-019-1611-7Peptide Deformylase (def) is essential in Mycobacterium smegmatis, but the essentiality is compensated by inactivation of methionine formylationNoga NaorOmer GadotMichal Meir0Daniel Barkan1The Ruth Rappaport Children’s Hospital, Rambam Health Care CampusKoret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem Rehovot CampusAbstract Background Co-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. Results Here we show by targeted deletion experiments that def can only be deleted from M. smegmatis when an additional copy is present; that prior deletion of tRNAfMet-Formyl Transferase (FMT, encoded by fmt) renders def completely dispensable; and that re-introduction of fmt into a Δdef mutant is not possible – constituting a definitive proof for the essentiality of def in mycobacteria. Conclusions Peptide deformylase is essential in M. smegmatis, but the fact that inactivation of fmt renders the gene completely dispensable, and thus any inhibitor of def useless, casts doubt on the usefulness of PDF as a drug-target in mycobacteria.http://link.springer.com/article/10.1186/s12866-019-1611-7MycobacteriaProtein synthesisCo-translationPeptide DeformylaseFormyl Transferase |
| spellingShingle | Noga Naor Omer Gadot Michal Meir Daniel Barkan Peptide Deformylase (def) is essential in Mycobacterium smegmatis, but the essentiality is compensated by inactivation of methionine formylation BMC Microbiology Mycobacteria Protein synthesis Co-translation Peptide Deformylase Formyl Transferase |
| title | Peptide Deformylase (def) is essential in Mycobacterium smegmatis, but the essentiality is compensated by inactivation of methionine formylation |
| title_full | Peptide Deformylase (def) is essential in Mycobacterium smegmatis, but the essentiality is compensated by inactivation of methionine formylation |
| title_fullStr | Peptide Deformylase (def) is essential in Mycobacterium smegmatis, but the essentiality is compensated by inactivation of methionine formylation |
| title_full_unstemmed | Peptide Deformylase (def) is essential in Mycobacterium smegmatis, but the essentiality is compensated by inactivation of methionine formylation |
| title_short | Peptide Deformylase (def) is essential in Mycobacterium smegmatis, but the essentiality is compensated by inactivation of methionine formylation |
| title_sort | peptide deformylase def is essential in mycobacterium smegmatis but the essentiality is compensated by inactivation of methionine formylation |
| topic | Mycobacteria Protein synthesis Co-translation Peptide Deformylase Formyl Transferase |
| url | http://link.springer.com/article/10.1186/s12866-019-1611-7 |
| work_keys_str_mv | AT noganaor peptidedeformylasedefisessentialinmycobacteriumsmegmatisbuttheessentialityiscompensatedbyinactivationofmethionineformylation AT omergadot peptidedeformylasedefisessentialinmycobacteriumsmegmatisbuttheessentialityiscompensatedbyinactivationofmethionineformylation AT michalmeir peptidedeformylasedefisessentialinmycobacteriumsmegmatisbuttheessentialityiscompensatedbyinactivationofmethionineformylation AT danielbarkan peptidedeformylasedefisessentialinmycobacteriumsmegmatisbuttheessentialityiscompensatedbyinactivationofmethionineformylation |