Nucleoside binding by a surface lipoprotein governs conjugative ICE acquisition in mycoplasmas
Derriche, M'hamed (Université de Toulouse. Laboratoire Interactions Hôtes-Agents Pathogènes)
Nouvel, Laurent Xavier (Université de Toulouse. Laboratoire Interactions Hôtes-Agents Pathogènes)
Fauvet, Calvin (Université de Toulouse. Laboratoire Interactions Hôtes-Agents Pathogènes)
Mach Casellas, Núria (Université de Toulouse. Laboratoire Interactions Hôtes-Agents Pathogènes)
Simon, Elisa (Université de Toulouse. Laboratoire Interactions Hôtes-Agents Pathogènes)
Pot, Gwendoline (Université de Toulouse. Laboratoire Interactions Hôtes-Agents Pathogènes)
Robert, Hortensia (Université de Toulouse. Laboratoire Interactions Hôtes-Agents Pathogènes)
Stella, Alexandre (Université de Toulouse. Institut de Pharmacologie et de Biologie Structurale)
De la Fe, Christina (Universidad de Murcia. Departamento de Sanidad Animal)
Maillard, Renaud (Université de Toulouse. Laboratoire Interactions Hôtes-Agents Pathogènes)
Torres Puig, Sergi (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Arfi, Yonathan (Université de Bordeaux. L’Institut national de recherche pour l'agriculture, l'alimentation et l'environnement)
Citti. Christine (Université de Toulouse. Laboratoire Interactions Hôtes-Agents Pathogènes)
Baranowski, Eric (Université de Toulouse. Laboratoire Interactions Hôtes-Agents Pathogènes)
Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular

Fecha:	2026
Resumen:	Integrative and conjugative elements (ICEs) are major mediators of horizontal gene transfer in bacteria. However, the role of recipient cells in their acquisition has received little attention. Using the ruminant pathogens Mycoplasma agalactiae and Mycoplasma bovis as minimal models, we combined genome-wide transposon mutagenesis with high-throughput mating assays to identify recipient factors required for ICE acquisition. The surface lipoprotein P48 emerged as the primary determinant of ICE uptake in both species. Structural and functional analyses revealed that P48 is the substrate-binding component of an ABC transporter with nucleoside-binding capacity. A single-point mutation that abolished nucleoside binding drastically reduced ICE acquisition, demonstrating that P48-mediated nucleoside recognition is essential for conjugative transfer. However, ICE uptake did not require nucleoside transport, as inactivation of the transporter permease blocked nucleoside analog toxicity but not ICE invasion. Loss of P48 also triggered transcriptional activation of vestigial ICE genes, suggesting that surface recognition affects the intracellular state of the recipient. Remarkably, ICE transfer from recipient-derived donors was unaffected by P48 loss, underscoring its acquisition-specific role. Together, these results reveal a previously unrecognized, surface-exposed recipient factor critical for efficient ICE transfer in mycoplasmas and identify nucleotide binding as a central function in conjugation. By demonstrating that recipient-encoded functions can directly control ICE dissemination, this work challenges the donor-centric paradigm of bacterial conjugation and suggests new strategies to restrict horizontal gene flow in pathogenic and synthetic mycoplasmas. IMPORTANCE Integrative and conjugative elements (ICEs) are mobile DNA elements that drive bacterial conjugation, a major process by which bacteria exchange genes. Although conjugation has been studied for decades, the focus has been almost exclusively on donor cells and the ICE itself, leaving the role of recipient cells largely overlooked. Using the wall-less ruminant pathogens Mycoplasma agalactiae and Mycoplasma bovis as minimal models, we discovered that a single recipient lipoprotein is required for efficient ICE uptake. Our data show that nucleoside recognition by P48, but not transport, is critical for conjugation, revealing an unexpected mechanistic link between nutrient sensing and gene acquisition. These findings shift the paradigm of conjugation from a donor-driven process to one jointly determined by donor and recipient functions. By identifying a recipient-encoded determinant of ICE transfer, this work opens new avenues to control horizontal gene flow in both pathogenic and engineered bacteria.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Horizontal gene transfer ; Integrative and conjugative element ; Bacterial conjugation ; Mycoplasma ; Mycoplasmopsis ; Nucleoside binding ; Lipoprotein ; Recipient cell
Publicado en:	mBio, Vol. 17, Num. 2 (February 2026) , art. e02939-25, ISSN 2150-7511

DOI: 10.1128/mbio.02939-25

20 p, 1.2 MB

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