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A Broadly Conserved Deoxycytidine Deaminase Protects Bacteria from Phage Infection

Geoffrey B. Severin, Brian Y. Hsueh, Clinton A. Elg, John A. Dover, Christopher R. Rhoades, Alex J. Wessel, Benjamin J. Ridenhour, Eva M. Top, Janani Ravi, Kristin N. Parent, Christopher M. Waters
doi: https://doi.org/10.1101/2021.03.31.437871
Geoffrey B. Severin
1Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA, 48824
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Brian Y. Hsueh
2Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA, 48824
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Clinton A. Elg
3Department of Biological Sciences, Institute for Bioinformatics and Evolutionary Studies, Bioinformatics and Computational Biology Program, University of Idaho, Moscow, Idaho, USA, 83844
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John A. Dover
1Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA, 48824
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Christopher R. Rhoades
2Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA, 48824
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Alex J. Wessel
2Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA, 48824
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Benjamin J. Ridenhour
4Department of Mathematics and Statistical Sciences, University of Idaho, Moscow, Idaho, USA, 83844
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Eva M. Top
3Department of Biological Sciences, Institute for Bioinformatics and Evolutionary Studies, Bioinformatics and Computational Biology Program, University of Idaho, Moscow, Idaho, USA, 83844
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Janani Ravi
5Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA, 48824
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Kristin N. Parent
1Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA, 48824
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Christopher M. Waters
2Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA, 48824
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  • For correspondence: watersc3@msu.edu
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SUMMARY

The El Tor biotype of Vibrio cholerae is responsible for perpetuating the longest cholera pandemic in recorded history (1961-current). The genomic islands VSP-1 and -2 are two understudied genetic features that distinguish El Tor from previous pandemics. To understand their utility, we calculated the co-occurrence of VSP genes across bacterial genomes. This analysis predicted the previously uncharacterized vc0175, herein renamed deoxycytidylate deaminase Vibrio (dcdV), is in a gene network with dncV, a cyclic GMP-AMP synthase involved in phage defense. DcdV consists of two domains, a P-loop kinase and a deoxycytidylate deaminase, that are required for the deamination of dCTP and dCMP, inhibiting phage predation by corrupting cellular nucleotide concentrations. Additionally, DcdV is post-translationally inhibited by a unique noncoding RNA encoded 5’ of the dcdV locus. DcdV homologs are conserved in bacteria and eukaryotes and our results identify V. cholerae DcdV as the founding member of a previously undescribed bacterial phage defense system.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 31, 2021.
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A Broadly Conserved Deoxycytidine Deaminase Protects Bacteria from Phage Infection
Geoffrey B. Severin, Brian Y. Hsueh, Clinton A. Elg, John A. Dover, Christopher R. Rhoades, Alex J. Wessel, Benjamin J. Ridenhour, Eva M. Top, Janani Ravi, Kristin N. Parent, Christopher M. Waters
bioRxiv 2021.03.31.437871; doi: https://doi.org/10.1101/2021.03.31.437871
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A Broadly Conserved Deoxycytidine Deaminase Protects Bacteria from Phage Infection
Geoffrey B. Severin, Brian Y. Hsueh, Clinton A. Elg, John A. Dover, Christopher R. Rhoades, Alex J. Wessel, Benjamin J. Ridenhour, Eva M. Top, Janani Ravi, Kristin N. Parent, Christopher M. Waters
bioRxiv 2021.03.31.437871; doi: https://doi.org/10.1101/2021.03.31.437871

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