Details

Autor(en) / Beteiligte

• Tal, Nitzan
• Morehouse, Benjamin R.
• Millman, Adi
• Stokar-Avihail, Avigail
• Avraham, Carmel
• Fedorenko, Taya
• Yirmiya, Erez
• Herbst, Ehud
• Brandis, Alexander
• Mehlman, Tevie
• Oppenheimer-Shaanan, Yaara
• Keszei, Alexander F.A.
• Shao, Sichen
• Amitai, Gil
• Kranzusch, Philip J.
• Sorek, Rotem

Titel

Cyclic CMP and cyclic UMP mediate bacterial immunity against phages

Ist Teil von

• Cell, 2021-11, Vol.184 (23), p.5728-5739.e16

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• The cyclic pyrimidines 3′,5′-cyclic cytidine monophosphate (cCMP) and 3′,5′-cyclic uridine monophosphate (cUMP) have been reported in multiple organisms and cell types. As opposed to the cyclic nucleotides 3′,5′-cyclic adenosine monophosphate (cAMP) and 3′,5′-cyclic guanosine monophosphate (cGMP), which are second messenger molecules with well-established regulatory roles across all domains of life, the biological role of cyclic pyrimidines has remained unclear. Here we report that cCMP and cUMP are second messengers functioning in bacterial immunity against viruses. We discovered a family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMP and cUMP following phage infection and demonstrate that these molecules activate immune effectors that execute an antiviral response. A crystal structure of a uridylate cyclase enzyme from this family explains the molecular mechanism of selectivity for pyrimidines as cyclization substrates. Defense systems encoding pyrimidine cyclases, denoted here Pycsar (pyrimidine cyclase system for antiphage resistance), are widespread in prokaryotes. Our results assign clear biological function to cCMP and cUMP as immunity signaling molecules in bacteria. [Display omitted] •cCMP and cUMP are secondary messengers in a bacterial immune system called Pycsar•cCMP and cUMP are produced following phage infection and activate immune effectors•Structure of a uridylate cyclase explains the mechanism of pyrimidine selectivity•Defense systems encoding pyrimidine cyclases are widespread in prokaryotes The cyclic pyrimidines cCMP and cUMP serve as second messengers to activate antiviral immunity in bacteria.