02080nas a2200385 4500000000100000008004100001260004400042653001700086653002700103653001300130653004300143653001500186653001700201100001700218700002700235700001200262700001300274700001100287700001500298700001300313700001500326700001000341700001800351700001500369700001100384700001700395700001400412700001300426700001500439245010600454856005900560300000900619520105200628022001401680 2023 d bSpringer Science and Business Media LLC10aCell Biology10aMicrobiology (medical)10aGenetics10aApplied Microbiology and Biotechnology10aImmunology10aMicrobiology1 aDulberger CL1 aGuerrero-Bustamante CA1 aOwen SV1 aWilson S1 aWuo MG1 aGarlena RA1 aSerpa LA1 aRussell DA1 aZhu J1 aBraunecker BJ1 aSquyres GR1 aBaym M1 aKiessling LL1 aGarner EC1 aRubin EJ1 aHatfull GF00aMycobacterial nucleoid-associated protein Lsr2 is required for productive mycobacteriophage infection uhttps://www.nature.com/articles/s41564-023-01333-x.pdf a1-163 a

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.

 a2058-5276