Download MendeleyUnraveling the prevalence and multifaceted roles of accessory peptide deformylases in bacterial adaptation and resistance.
Lamberioux, M., Ducos-Galand, M., Kaminski, P.A., Littner, E., Betton, J.M., Mechaly, A., Haouz, A., Mazel, D.(2025) Mol Biol Evol
- PubMed: 41316864
- DOI: https://doi.org/10.1093/molbev/msaf311
- Primary Citation of Related Structures:
9QFR, 9QFT - PubMed Abstract:
Peptide deformylases (PDFs) are enzymes that are essential for bacterial viability and attractive targets for antibiotic development. Yet, despite their conserved function, many bacteria encode multiple PDFs, a genomic feature whose prevalence and implications remain largely unexplored. Here, we reveal that nearly half of all bacterial genomes carry more than one PDF gene, frequently embedded within mobile genetic elements such as plasmids and integrons. In Vibrio cholerae, the accessory PDF (Def2VCH) confers reduced susceptibility to actinonin (ACT), the most studied PDF inhibitor, while still supporting bacterial growth in absence of the canonical PDF copies (Def1VCH). Crystallographic analysis shows that this reduced susceptibility stems from an arginine-to-tyrosine substitution that probably reduces ACT binding. Strikingly, this resistance signature is shared by integron-encoded PDFs, and transfer of an integron-encoded PDF cassette from Pseudoxanthomonas into a susceptible V. cholerae is sufficient to abolish ACT susceptibility. These findings reveal a hidden reservoir of resistance within the bacterial mobilome and shed light on potential mechanisms of bacterial resilience to environmental PDF inhibitors.
- Institut Pasteur, Université Paris Cité, Unité Plasticité du Génome Bactérien, CNRS UMR3525, Paris, France.
Organizational Affiliation:
