Mycobacterial nucleoid-associated protein Lsr2 is required for productive mycobacteriophage infection
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s41564-023-01333-x.pdf
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Published version
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11.62 MB
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Author(s)
Dulberger, Charles L
Guerrero-Bustamante, Carlos A
Owen, Siân V
Wilson, Sean
Wuo, Michael G
Garlena, Rebecca A
Serpa, Lexi A
Russell, Daniel A
Zhu, Junhao
Braunecker, Ben J
Date Issued
February 23, 2023
Journal
Nature Microbiology
Publisher
Springer Nature
Citation
Dulberger, C.L., Guerrero-Bustamante, C.A., Owen, S.V. et al. Mycobacterial nucleoid-associated protein Lsr2 is required for productive mycobacteriophage infection. Nat Microbiol 8, 695–710 (2023).
Version
Final published version
Abstract
Mycobacteriophages are a diverse group of viruses infecting Mycobacterium with substantial therapeutic potential. However, as this potential becomes realized, the molecular details of phage infection and mechanisms of resistance remain ill-defined. Here we use live-cell fluorescence microscopy to visualize the spatiotemporal dynamics of mycobacteriophage infection in single cells and populations, showing that infection is dependent on the host nucleoid-associated Lsr2 protein. Mycobacteriophages preferentially adsorb at Mycobacterium smegmatis sites of new cell wall synthesis and following DNA injection, Lsr2 reorganizes away from host replication foci to establish zones of phage DNA replication (ZOPR). Cells lacking Lsr2 proceed through to cell lysis when infected but fail to generate consecutive phage bursts that trigger epidemic spread of phage particles to neighbouring cells. Many mycobacteriophages code for their own Lsr2-related proteins, and although their roles are unknown, they do not rescue the loss of host Lsr2.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1038/s41564-023-01333-x
