Campylobacter phages use hypermutable polyG tracts to create phenotypic diversity and evade bacterial resistance

Martine C.Holst Sørensen*, Amira Vitt, Horst Neve, Matteo Soverini, Stephen James Ahern, Jochen Klumpp, Lone Brøndsted

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

Phase variation is a common mechanism for creating phenotypic heterogeneity of surface structures in bacteria important for niche adaptation. In Campylobacter, phase variation occurs by random variation in hypermutable homonucleotide 7–11 G (polyG) tracts. To elucidate how phages adapt to phase-variable hosts, we study Fletchervirus phages infecting Campylobacter dependent on a phase-variable receptor. Our data demonstrate that Fletcherviruses mimic their host and encode hypermutable polyG tracts, leading to phase-variable expression of two of four receptor-binding proteins. This creates phenotypically diverse phage populations, including a sub-population that infects the bacterial host when the phase-variable receptor is not expressed. Such population dynamics of both phage and host promote co-existence in a shared niche. Strikingly, we identify polyG tracts in more than 100 phage genera, infecting more than 70 bacterial species. Future experimental work may confirm phase variation as a widespread strategy for creating phenotypically diverse phage populations.

OriginalsprogEngelsk
Artikelnummer109214
TidsskriftCell Reports
Vol/bind35
Udgave nummer10
Antal sider20
ISSN2211-1247
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
We thank laboratory technician Vi Phuong Thi Nguyen for general technical assistance, Dr. Derek Pickard for valued input on phage DNA isolation, Dr. Athina Zampara for valued advice on protein expression and purification, and Professor Rob Lavigne for valued input to the manuscript. We are grateful to Dr. Anna Bratus-Neuenschwander and the staff of the Functional Genomics Center Zurich for excellent technical assistance with phage genome sequencing. Angela Back (Max Rubner-Institut) is acknowledged for her technical assistance with the electron microscopy. This work was supported by the Danish Council for Independent Research (grant 4184-00109B ), the Danish AgriFish Agency of Ministry of Environment and Food (grant 34009-14-0873 ), and Intralytix, Inc . J.K. is grateful to Martin J. Loessner for financial support (ETH Zurich funds 23651 ).

Funding Information:
We thank laboratory technician Vi Phuong Thi Nguyen for general technical assistance, Dr. Derek Pickard for valued input on phage DNA isolation, Dr. Athina Zampara for valued advice on protein expression and purification, and Professor Rob Lavigne for valued input to the manuscript. We are grateful to Dr. Anna Bratus-Neuenschwander and the staff of the Functional Genomics Center Zurich for excellent technical assistance with phage genome sequencing. Angela Back (Max Rubner-Institut) is acknowledged for her technical assistance with the electron microscopy. This work was supported by the Danish Council for Independent Research (grant 4184-00109B), the Danish AgriFish Agency of Ministry of Environment and Food (grant 34009-14-0873), and Intralytix, Inc. J.K. is grateful to Martin J. Loessner for financial support (ETH Zurich funds 23651). Conceptualization, M.C.H.S. and L.B.; methodology, M.C.H.S. A.V. H.N. and M.S.; investigation, M.C.H.S, A.V. H.N. M.S. S.J.A. and J.K.; formal analysis, M.C.H.S. and M.S.; software, M.S.; writing ? original draft, M.C.H.S. and L.B.; funding acquisition, M.C.H.S. and L.B.; resources, M.C.H.S. L.B. H.N. M.S. and J.K.; supervision, M.C.H.S. The authors declare no competing interests. The salary of M.C.H.S was partially funded by Intralytix, Inc. which had no influence on the design or conclusions of the present work.

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