Bacteria elicit a phage tolerance response subsequent to infection of their neighbors

Elhanan Tzipilevich; Osher Pollak-Fiyaksel; Bushra Shraiteh; Sigal Ben-Yehuda

doi:10.15252/embj.2021109247

Bacteria elicit a phage tolerance response subsequent to infection of their neighbors

Elhanan Tzipilevich, Osher Pollak-Fiyaksel, Bushra Shraiteh, Sigal Ben-Yehuda^*

^*Corresponding author for this work

Department of Microbiology and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Appearance of plaques on a bacterial lawn is a sign of successive rounds of bacteriophage infection. Yet, mechanisms evolved by bacteria to limit plaque spread have been hardly explored. Here, we investigated the dynamics of plaque development by lytic phages infecting the bacterium Bacillus subtilis. We report that plaque expansion is followed by a constriction phase owing to bacterial growth into the plaque zone. This phenomenon exposed an adaptive process, herein termed "phage tolerance response", elicited by non-infected bacteria upon sensing infection of their neighbors. The temporary phage tolerance is executed by the stress-response RNA polymerase sigma factor σ^X (SigX). Artificial expression of SigX prior to phage attack largely eliminates infection. SigX tolerance is primarily conferred by activation of the dlt operon, encoding enzymes that catalyze D-alanylation of cell wall teichoic acid polymers, the major attachment sites for phages infecting Gram-positive bacteria. D-alanylation impedes phage binding and hence infection, thus enabling the uninfected bacteria to form a protective shield opposing phage spread.

Original language	American English
Article number	e109247
Journal	EMBO Journal
Volume	41
Issue number	3
DOIs	https://doi.org/10.15252/embj.2021109247
State	Published - Feb 2022

Bibliographical note

Funding Information:
We thank R. Losick (Harvard University, USA), I. Rosenshine and A. Rouvinski (Hebrew University, Israel), and members of the Ben-Yehuda laboratory for valuable discussions. We thank N. Balaban and her laboratory members (Hebrew University, Israel) for assistance with the automated plaque scanning procedure. We are grateful to P. Tavers (Gif-sur-Yvette, France), J. Helmann (Cornell University, USA), and D. Rudner (Harvard University, USA) for providing strains. Artwork in Fig 3 and synopsis was prepared using BioRender (Agreement Number II2338U308, CN2368MHCR). This work was supported by the NSF/BSF-United States-Israel Binational Science Foundation (2017672), and the ERC Synergy grant (810186) awarded to S. B.-Y. The authors declare that they have no conflict of interest.

Funding Information:
We thank R. Losick (Harvard University, USA), I. Rosenshine and A. Rouvinski (Hebrew University, Israel), and members of the Ben‐Yehuda laboratory for valuable discussions. We thank N. Balaban and her laboratory members (Hebrew University, Israel) for assistance with the automated plaque scanning procedure. We are grateful to P. Tavers (Gif‐sur‐Yvette, France), J. Helmann (Cornell University, USA), and D. Rudner (Harvard University, USA) for providing strains. Artwork in Fig 3 and synopsis was prepared using BioRender (Agreement Number II2338U308, CN2368MHCR). This work was supported by the NSF/BSF‐United States‐Israel Binational Science Foundation (2017672), and the ERC Synergy grant (810186) awarded to S. B.‐Y.

Publisher Copyright:
© 2021 The Authors

Keywords

Bacillus subtilis/metabolism
Bacteriophages/pathogenicity
Host-Pathogen Interactions
Operon
Sigma Factor/metabolism

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10.15252/embj.2021109247

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title = "Bacteria elicit a phage tolerance response subsequent to infection of their neighbors",

abstract = "Appearance of plaques on a bacterial lawn is a sign of successive rounds of bacteriophage infection. Yet, mechanisms evolved by bacteria to limit plaque spread have been hardly explored. Here, we investigated the dynamics of plaque development by lytic phages infecting the bacterium Bacillus subtilis. We report that plaque expansion is followed by a constriction phase owing to bacterial growth into the plaque zone. This phenomenon exposed an adaptive process, herein termed {"}phage tolerance response{"}, elicited by non-infected bacteria upon sensing infection of their neighbors. The temporary phage tolerance is executed by the stress-response RNA polymerase sigma factor σX (SigX). Artificial expression of SigX prior to phage attack largely eliminates infection. SigX tolerance is primarily conferred by activation of the dlt operon, encoding enzymes that catalyze D-alanylation of cell wall teichoic acid polymers, the major attachment sites for phages infecting Gram-positive bacteria. D-alanylation impedes phage binding and hence infection, thus enabling the uninfected bacteria to form a protective shield opposing phage spread.",

keywords = "Bacillus subtilis/metabolism, Bacteriophages/pathogenicity, Host-Pathogen Interactions, Operon, Sigma Factor/metabolism",

author = "Elhanan Tzipilevich and Osher Pollak-Fiyaksel and Bushra Shraiteh and Sigal Ben-Yehuda",

note = "Funding Information: We thank R. Losick (Harvard University, USA), I. Rosenshine and A. Rouvinski (Hebrew University, Israel), and members of the Ben-Yehuda laboratory for valuable discussions. We thank N. Balaban and her laboratory members (Hebrew University, Israel) for assistance with the automated plaque scanning procedure. We are grateful to P. Tavers (Gif-sur-Yvette, France), J. Helmann (Cornell University, USA), and D. Rudner (Harvard University, USA) for providing strains. Artwork in Fig 3 and synopsis was prepared using BioRender (Agreement Number II2338U308, CN2368MHCR). This work was supported by the NSF/BSF-United States-Israel Binational Science Foundation (2017672), and the ERC Synergy grant (810186) awarded to S. B.-Y. The authors declare that they have no conflict of interest. Funding Information: We thank R. Losick (Harvard University, USA), I. Rosenshine and A. Rouvinski (Hebrew University, Israel), and members of the Ben‐Yehuda laboratory for valuable discussions. We thank N. Balaban and her laboratory members (Hebrew University, Israel) for assistance with the automated plaque scanning procedure. We are grateful to P. Tavers (Gif‐sur‐Yvette, France), J. Helmann (Cornell University, USA), and D. Rudner (Harvard University, USA) for providing strains. Artwork in Fig 3 and synopsis was prepared using BioRender (Agreement Number II2338U308, CN2368MHCR). This work was supported by the NSF/BSF‐United States‐Israel Binational Science Foundation (2017672), and the ERC Synergy grant (810186) awarded to S. B.‐Y. Publisher Copyright: {\textcopyright} 2021 The Authors",

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doi = "10.15252/embj.2021109247",

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N2 - Appearance of plaques on a bacterial lawn is a sign of successive rounds of bacteriophage infection. Yet, mechanisms evolved by bacteria to limit plaque spread have been hardly explored. Here, we investigated the dynamics of plaque development by lytic phages infecting the bacterium Bacillus subtilis. We report that plaque expansion is followed by a constriction phase owing to bacterial growth into the plaque zone. This phenomenon exposed an adaptive process, herein termed "phage tolerance response", elicited by non-infected bacteria upon sensing infection of their neighbors. The temporary phage tolerance is executed by the stress-response RNA polymerase sigma factor σX (SigX). Artificial expression of SigX prior to phage attack largely eliminates infection. SigX tolerance is primarily conferred by activation of the dlt operon, encoding enzymes that catalyze D-alanylation of cell wall teichoic acid polymers, the major attachment sites for phages infecting Gram-positive bacteria. D-alanylation impedes phage binding and hence infection, thus enabling the uninfected bacteria to form a protective shield opposing phage spread.

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ER -

Bacteria elicit a phage tolerance response subsequent to infection of their neighbors

Abstract

Bibliographical note

Keywords

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