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Universitat Autònoma de Barcelona
Institut de Biotecnologia i de Biomedicina

New article: "Nucleoside binding by a surface lipoprotein governs conjugative ICE acquisition in mycoplasmas"

08 Jan 2026
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Research Group: Molecular Biology

Three-dimensional structures of PnrA and P48, from S. pnemoniae and M. agalactiae, respectively

Abstract:

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.

Article data:

Derriche M, Nouvel LX, Fauvet C, Mach N, Simon E, Pot G, Robert H, Stella A, de la Fe C, Maillard R, Torres-Puig S, Arfi Y, Citti C, Baranowski E. 0. Nucleoside binding by a surface lipoprotein governs conjugative ICE acquisition in mycoplasmas. mBio 0:e02939-25. https://doi.org/10.1128/mbio.02939-25

DOI: 10.1128/mbio.02939-25

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