Cyclic CMP and cyclic UMP mediate bacterial immunity against phages

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

doi:10.1016/j.cell.2021.09.031

Cited by 199 publications

(152 citation statements)

References 71 publications

Supporting

Mentioning

145

Contrasting

Order By: Relevance

“…These results suggest that detection – either direct or indirect – of the late-expressed major capsid protein activates the CdnA enzyme, which is consistent with previous data showing cGAMP levels increasing 40 minutes after P1 phage infection in E. coli (Cohen et al, 2019). Moreover, these mutations mirror the recent identification of major capsid mutations in phage T5, which enables evasion of the Pycsar cCMP-based anti-phage bacterial immune system (Tal et al, 2021). The aforementioned study also noted that over-expression of the T5 WT major capsid protein did not induce Pyscar-specific toxicity (Tal et al, 2020), which was similarly observed in our CBASS model system.…”

Section: Discussionmentioning

confidence: 60%

Bacteriophages antagonize cGAS-like immunity in bacteria

Huiting

Athukoralage

Guan

et al. 2022

Preprint

View full text Add to dashboard Cite

The recently discovered cyclic-oligonucleotide-based anti-phage signaling system (CBASS) is related to eukaryotic cGAS-STING anti-viral immunity and is present in diverse prokaryotes. However, our understanding of how CBASS detects, inhibits, and co-evolves with phages is limited because CBASS function has only been studied in reconstituted heterologous systems. Here, we identify a phage-encoded CBASS antagonist (acbIIA1, anti-cbass type II-A gene 1) necessary for phage replication in the presence of endogenous CBASS immunity in Pseudomonas aeruginosa. acbIIA1 homologs are encoded by numerous lytic and temperate phages infecting Gram-negative bacteria. Deletion of acbIIA1 renders multiple phages susceptible to CBASS, but phages can then escape immune function via mutations in the major capsid gene. These mutants suggest that CBASS is activated by, or targets, the late-expressed phage capsid. Together, we establish a native model system to study CBASS and identify a common phage-encoded CBASS antagonist, demonstrating that CBASS is a bona fide anti-phage immune system in nature.

show abstract

Section: Discussionmentioning

confidence: 60%

Bacteriophages antagonize cGAS-like immunity in bacteria

Huiting

Athukoralage

Guan

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…3′,5′-cCMP and 3′,5′-cUMP were just recently identified to play an important role as signaling molecules in prokaryotic phage-defense systems ( Tal et al, 2021 ). A recently performed phylogenetic analysis of proteins containing pyrimidine cyclase domains revealed that these types of enzymes are also found in few euryarchaeal species ( Tal et al, 2021 ). However, BLAST searches of these identified putative euryarchaeal pyrimidine cyclases in the proteome of H. volcanii yielded no hit.…”

Section: Resultsmentioning

confidence: 99%

“…However, BLAST searches of these identified putative euryarchaeal pyrimidine cyclases in the proteome of H. volcanii yielded no hit. The same applies when experimentally characterized bacterial pyrimidine cyclases ( Tal et al, 2021 ) were used as template. This observation might suggest the existence of additional and more distantly to the recently discovered pyrimidine cyclases related types of specific cytidylate/uridylate cyclases.…”

Section: Resultsmentioning

confidence: 99%

Putative Nucleotide-Based Second Messengers in the Archaeal Model Organisms Haloferax volcanii and Sulfolobus acidocaldarius

et al. 2021

View full text Add to dashboard Cite

Research on nucleotide-based second messengers began in 1956 with the discovery of cyclic adenosine monophosphate (3′,5′-cAMP) by Earl Wilbur Sutherland and his co-workers. Since then, a broad variety of different signaling molecules composed of nucleotides has been discovered. These molecules fulfill crucial tasks in the context of intracellular signal transduction. The vast majority of the currently available knowledge about nucleotide-based second messengers originates from model organisms belonging either to the domain of eukaryotes or to the domain of bacteria, while the archaeal domain is significantly underrepresented in the field of nucleotide-based second messenger research. For several well-stablished eukaryotic and/or bacterial nucleotide-based second messengers, it is currently not clear whether these signaling molecules are present in archaea. In order to shed some light on this issue, this study analyzed cell extracts of two major archaeal model organisms, the euryarchaeon Haloferax volcanii and the crenarchaeon Sulfolobus acidocaldarius, using a modern mass spectrometry method to detect a broad variety of currently known nucleotide-based second messengers. The nucleotides 3′,5′-cAMP, cyclic guanosine monophosphate (3′,5′-cGMP), 5′-phosphoadenylyl-3′,5′-adenosine (5′-pApA), diadenosine tetraphosphate (Ap4A) as well as the 2′,3′-cyclic isomers of all four RNA building blocks (2′,3′-cNMPs) were present in both species. In addition, H. volcanii cell extracts also contain cyclic cytosine monophosphate (3′,5′-cCMP), cyclic uridine monophosphate (3′,5′-cUMP) and cyclic diadenosine monophosphate (3′,5′-c-di-AMP). The widely distributed bacterial second messengers cyclic diguanosine monophosphate (3′,5′-c-di-GMP) and guanosine (penta-)/tetraphosphate [(p)ppGpp] could not be detected. In summary, this study gives a comprehensive overview on the presence of a large set of currently established or putative nucleotide-based second messengers in an eury- and a crenarchaeal model organism.

show abstract

“…It can be expected that there are many more interesting regulatory nucleotide molecules to discover in the future. An example for the dynamics of this part of the cyclic nucleotide field is the most recent finding that cCMP and cUMP, which had previously been detected in various mammalian tissues [ 75 ] mediate bacterial immunity against phages [ 76 ].…”

Section: Introductionmentioning

confidence: 99%

Cyclic Nucleotide (cNMP) Analogues: Past, Present and Future

Maronde

2021

IJMS

View full text Add to dashboard Cite

Cyclic nucleotides are important second messengers involved in cellular events, and analogues of this type of molecules are promising drug candidates. Some cyclic nucleotide analogues have become standard tools for the investigation of biochemical and physiological signal transduction pathways, such as the Rp-diastereomers of adenosine and guanosine 3′,5′-cyclic monophosphorothioate, which are competitive inhibitors of cAMP- and cGMP-dependent protein kinases. Next generation analogues exhibit a higher membrane permeability, increased resistance against degradation, and improved target specificity, or are caged or photoactivatable for fast and/or targeted cellular imaging. Novel specific nucleotide analogues activating or inhibiting cyclic nucleotide-dependent ion channels, EPAC/GEF proteins, and bacterial target molecules have been developed, opening new avenues for basic and applied research. This review provides an overview of the current state of the field, what can be expected in the future and some practical considerations for the use of cyclic nucleotide analogues in biological systems.

show abstract

Cyclic CMP and cyclic UMP mediate bacterial immunity against phages

Cited by 199 publications

References 71 publications

Bacteriophages antagonize cGAS-like immunity in bacteria

Bacteriophages antagonize cGAS-like immunity in bacteria

Putative Nucleotide-Based Second Messengers in the Archaeal Model Organisms Haloferax volcanii and Sulfolobus acidocaldarius

Cyclic Nucleotide (cNMP) Analogues: Past, Present and Future

Contact Info

Product

Resources

About