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bioRxiv · 10.1101/2020.04.27.058388

Systematic Discovery of Salmonella Phage-Host Interactions via High-Throughput Genome-Wide Screens

Adler, B. A.·Zhong, C.·Liu, H.·Kutter, E.·Deutschbauer, A. M.·Mutalik, V. K.·Arkin, A. P.
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Abstract

Though bacteriophages (phages) are known to play a crucial role in bacterial fitness and virulence, our knowledge about the genetic basis of their interaction, cross-resistance and host-range is sparse. Here, we employed genome-wide screens in Salmonella enterica serovar Typhimurium to discover host determinants involved in resistance to eleven diverse lytic phages including 4 new phages isolated from a therapeutic phage cocktail. We uncovered 301 diverse host factors essential in phage infection, many of which are shared between multiple phages demonstrating potential cross-resistance mechanisms. We validate many of these novel findings and uncover the intricate interplay between RpoS, the virulence-associated general stress response sigma factor and RpoN, the nitrogen starvation sigma factor in phage cross-resistance. Finally, the infectivity pattern of eleven phages across a panel of 23 genome sequenced Salmonella strains indicates that additional constraints and interactions beyond the host factors uncovered here define the phage host range.

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Adler, B. A., Zhong, C., Liu, H., Kutter, E., Deutschbauer, A. M., Mutalik, V. K., Arkin, A. P.. 2020-04-28. Systematic Discovery of Salmonella Phage-Host Interactions via High-Throughput Genome-Wide Screens. https://doi.org/10.1101/2020.04.27.058388

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