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

Jan Böhning, Miles Graham, Suzanne C. Letham, Luke K. Davis, Ulrike Schulze, Phillip J. Stansfeld, Robin A. Corey, Philip Pearce, Abul K. Tarafder () and Tanmay A. M. Bharat ()
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Jan Böhning: MRC Laboratory of Molecular Biology
Miles Graham: MRC Laboratory of Molecular Biology
Suzanne C. Letham: MRC Laboratory of Molecular Biology
Luke K. Davis: University College London
Ulrike Schulze: MRC Laboratory of Molecular Biology
Phillip J. Stansfeld: University of Warwick
Robin A. Corey: University of Oxford
Philip Pearce: University College London
Abul K. Tarafder: MRC Laboratory of Molecular Biology
Tanmay A. M. Bharat: MRC Laboratory of Molecular Biology

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-44160-8

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