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A Broadly Conserved Deoxycytidine Deaminase Protects Bacteria from Phage Infection

Geoffrey B. Severin^1#@, Brian Y. Hsueh^2#, Clinton A. Elg³, John A. Dover¹, Christopher R. Rhoades², Alex J. Wessel², Benjamin J. Ridenhour⁴, Eva M. Top³, Janani Ravi⁵, Kristin N. Parent¹, and Christopher M. Waters^2*

¹Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA, 48824. ²Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA, 48824. ³Department of Biological Sciences, Institute for Bioinformatics and Evolutionary Studies, Bioinformatics and Computational Biology Program, University of Idaho, Moscow, Idaho, USA, 83844. ⁴Department of Mathematics and Statistical Sciences, University of Idaho, Moscow, Idaho, USA, 83844. ⁵Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA, 48824.
^@Current address: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, 48109.

^#These authors contributed equally to this work.

*Corresponding Author: 5180 Biomedical and Physical Sciences, 567 Wilson Road, East Lansing, MI 48824. Telephone: 517-884-5360. E-mail: watersc3@msu.edu

Running Title: A Broadly Conserved Cytidine Deaminase Protects Bacteria from Phage Infection

Abstract

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.

Keywords

cytidine deaminase, phage, genomic island, toxin-antitoxin, thymineless death, APOBEC

Citation

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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