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Biophysical basis of filamentous phage tactoid-mediated antibiotic tolerance in P. aeruginosa.

Published version
Peer-reviewed

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Abstract

Inoviruses are filamentous phages infecting numerous prokaryotic phyla. Inoviruses can self-assemble into mesoscale structures with liquid-crystalline order, termed tactoids, which protect bacterial cells in Pseudomonas aeruginosa biofilms from antibiotics. Here, we investigate the structural, biophysical, and protective properties of tactoids formed by the P. aeruginosa phage Pf4 and Escherichia coli phage fd. A cryo-EM structure of the capsid from fd revealed distinct biochemical properties compared to Pf4. Fd and Pf4 formed tactoids with different morphologies that arise from differing phage geometries and packing densities, which in turn gave rise to different tactoid emergent properties. Finally, we showed that tactoids formed by either phage protect rod-shaped bacteria from antibiotic treatment, and that direct association with a tactoid is required for protection, demonstrating the formation of a diffusion barrier by the tactoid. This study provides insights into how filamentous molecules protect bacteria from extraneous substances in biofilms and in host-associated infections.

Description

Acknowledgements: T.A.M.B. would like to thank UKRI MRC (Programme MC_UP_1201/31), the Human Frontier Science Programme (Grant RGY0074/2021), the EPSRC (Grant EP/V026623/1), the Vallee Research Foundation, the European Molecular Biology Organisation, the Leverhulme Trust and the Lister Institute for Preventative Medicine for support. P.P. is supported by a UKRI Future Leaders Fellowship [MR/V022385/1]. This project made use of time on ARCHER2 granted via the UK High-End Computing Consortium for Biomolecular Simulation, HECBioSim (www.hecbiosim.ac.uk), supported by EPSRC (grant no. EP/R029407/1). We would like to thank Professor Mark Sansom and The Kavli Institute Structural Bioinformatics and Computational Biochemistry unit at the University of Oxford for facilitating the Molecular Dynamics performed in this research. We thank Jeanne Salje and Paul Edelstein for critical comments and the MRC-LMB cryo-EM and light microscopy facility for technical support.

Keywords

Anti-Bacterial Agents, Pseudomonas aeruginosa, Pseudomonas Phages, Inovirus, Bacteriophages, Bacteria, Biofilms

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

14

Publisher

Springer Science and Business Media LLC
Sponsorship
RCUK | Medical Research Council (MRC) (MC_UP_1201/31)
RCUK | Engineering and Physical Sciences Research Council (EPSRC) (EP/V026623/1)