Plasmid-encoded host reprogramming promotes plasmid dissemination
Year: 2026
Type: preprint
Abstract: Conjugative plasmids are major drivers of antibiotic resistance dissemination, yet how newly transferred plasmids establish in recipient cells remains poorly understood. Here we investigate YfjB, a previously uncharacterized conserved leading-region protein, which is zygotically induced immediately after plasmid entry and acts specifically during the earliest post-transfer stages. Multi-omics analyses reveal that YfjB reprograms host transcription, triggering extensive metabolic rewiring that compensates the transient fitness cost of plasmid acquisition. Structural analyses show that YfjB is a ParB-like protein containing a CTP-binding domain and a helix-turn-helix DNA-binding motif, linked to a previously uncharacterized dimerization module that forms a V-shaped clamp-like architecture compatible with DNA loading. Consistently, live-cell imaging reveals nucleoid-associated foci in transconjugants, and ChIP-seq identifies multiple chromosomal binding sites. We therefore rename the protein HerB (Host Expression Reprogrammer, ParB-like). More broadly, our findings reveal how mobile genetic elements facilitate their dissemination by transiently subverting host physiology.
Authors: Chloé Virolle, Sibylle Ferrarin, Gaël Panis, Yannick Baffert, Annick Dedieu-Berne, Jérémy Guérin, Julien Cayron, Daouda A K Traoré, Sofía Martínez-Absalón, Rania Zenati, Frédéric Delolme, Adeline Page, Sarah Bigot, Yoshiharu Yamaichi, Allison Lopatkin, Patrick H. Viollier, David Burstein, Laurent Terradot, Christian Lesterlin
Institutions: Lyon 1 Université, Centre National de la Recherche Scientifique, Inserm, Microbiologie moléculaire et biochimie structurale, University of Geneva, Université des Sciences, des Techniques et des Technologies de Bamako, Institut Laue-Langevin, Keele University, University of Rochester, École Normale Supérieure de Lyon, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, Institut de Biologie Intégrative de la Cellule, Tel Aviv University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: CBH-EUR-GS, Determinants underlying horizontal gene transfer-mediated pathogen success, G476804481, Gene expression Reprogramming in the new host cell during bacterial conjugation by the YfjB plasmid-encoded factor, Structural basis of Helicobacter pylori type IV secretion system, Mechanisms driving the dissemination of multidrug resistance plasmids
OpenAlex ID: W7167706502