Phage Paride can kill dormant, antibiotic-tolerant cells of Pseudomonas aeruginosa by direct lytic replication

Enea Maffei, Anne-Kathrin Woischnig, Marco R. Burkolter, Yannik Heyer, Dorentina Humolli, Nicole Thürkauf, Thomas Bock, Alexander Schmidt, Pablo Manfredi, Adrian Egli, Nina Khanna, Urs Jenal and Alexander Harms ()
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Enea Maffei: Biozentrum, University of Basel
Anne-Kathrin Woischnig: University and University Hospital Basel
Marco R. Burkolter: Biozentrum, University of Basel
Yannik Heyer: Biozentrum, University of Basel
Dorentina Humolli: Institute of Food, Nutrition and Health, D-HEST, ETH Zurich
Nicole Thürkauf: Biozentrum, University of Basel
Thomas Bock: Biozentrum, University of Basel
Alexander Schmidt: Biozentrum, University of Basel
Pablo Manfredi: Biozentrum, University of Basel
Adrian Egli: University Hospital Basel
Nina Khanna: Institute of Food, Nutrition and Health, D-HEST, ETH Zurich
Urs Jenal: Biozentrum, University of Basel
Alexander Harms: Biozentrum, University of Basel

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Bacteriophages are ubiquitous viral predators that have primarily been studied using fast-growing laboratory cultures of their bacterial hosts. However, microbial life in nature is mostly in a slow- or non-growing, dormant state. Here, we show that diverse phages can infect deep-dormant bacteria and suspend their replication until the host resuscitates (“hibernation”). However, a newly isolated Pseudomonas aeruginosa phage, named Paride, can directly replicate and induce the lysis of deep-dormant hosts. While non-growing bacteria are notoriously tolerant to antibiotic drugs, the combination with Paride enables the carbapenem meropenem to eradicate deep-dormant cultures in vitro and to reduce a resilient bacterial infection of a tissue cage implant in mice. Our work might inspire new treatments for persistent bacterial infections and, more broadly, highlights two viral strategies to infect dormant bacteria (hibernation and direct replication) that will guide future studies on phage-host interactions.

Date: 2024
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DOI: 10.1038/s41467-023-44157-3

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