A Broadly Conserved Deoxycytidine Deaminase Protects Bacteria from Phage Infection

Severin, G. B.; Hsueh, B. Y.; Elg, C. A.; Dover, J. A.; Rhoades, C. R.; Wessel, A. J.; Ridenhour, B. J.; Top, E. M.; Ravi, J.; Parent, K. N.; Waters, C. M.

doi:10.1101/2021.03.31.437871

bioRxiv · 10.1101/2021.03.31.437871

A Broadly Conserved Deoxycytidine Deaminase Protects Bacteria from Phage Infection

Severin, G. B.·Hsueh, B. Y.·Elg, C. A.·Dover, J. A.·Rhoades, C. R.·Wessel, A. J.·Ridenhour, B. J.·Top, E. M.·Ravi, J.·Parent, K. N.·Waters, C. M.

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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.

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Severin, G. B., Hsueh, B. Y., Elg, C. A., Dover, J. A., Rhoades, C. R., Wessel, A. J., Ridenhour, B. J., Top, E. M., Ravi, J., Parent, K. N., Waters, C. M.. 2021-03-31. A Broadly Conserved Deoxycytidine Deaminase Protects Bacteria from Phage Infection. https://doi.org/10.1101/2021.03.31.437871

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