A phytobacterial TIR domain effector manipulates NAD<sup>+</sup> to promote virulence

Eastman, Samuel; Smith, Trevor; Zaydman, Mark A.; Kim, Panya; Martinez, Samuel; Damaraju, Neha; DiAntonio, Aaron; Milbrandt, Jeffrey; Clemente, Thomas E.; Alfano, James R.; Guo, Ming

doi:10.1111/nph.17805

Cited by 54 publications

(72 citation statements)

References 82 publications

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“…In accordance, TIR domain-containing proteins appear to produce several species of v-cADPR that have different effects. It was shown that v-cADPR produced by AbTir is different from that produced by HopAM1 (a P. syringae effector suppressing plant innate immunity) (Eastman et al 2021). Interestingly, v-cADPR produced by a plant TIR domain-containing protein (BdTIR) was found to activate the bacterial antiphage defence system (Ofir et al 2021).…”

Section: Products Of the Nad + -Cleavage Reaction Are Required For Downstream Immune Signallingmentioning

confidence: 99%

Structural basis of NLR activation and innate immune signalling in plants

et al. 2022

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Animals and plants have NLRs (nucleotide-binding leucine-rich repeat receptors) that recognize the presence of pathogens and initiate innate immune responses. In plants, there are three types of NLRs distinguished by their N-terminal domain: the CC (coiled-coil) domain NLRs, the TIR (Toll/interleukin-1 receptor) domain NLRs and the RPW8 (resistance to powdery mildew 8)-like coiled-coil domain NLRs. CC-NLRs (CNLs) and TIR-NLRs (TNLs) generally act as sensors of effectors secreted by pathogens, while RPW8-NLRs (RNLs) signal downstream of many sensor NLRs and are called helper NLRs. Recent studies have revealed three dimensional structures of a CNL (ZAR1) including its inactive, intermediate and active oligomeric state, as well as TNLs (RPP1 and ROQ1) in their active oligomeric states. Furthermore, accumulating evidence suggests that members of the family of lipase-like EDS1 (enhanced disease susceptibility 1) proteins, which are uniquely found in seed plants, play a key role in providing a link between sensor NLRs and helper NLRs during innate immune responses. Here, we summarize the implications of the plant NLR structures that provide insights into distinct mechanisms of action by the different sensor NLRs and discuss plant NLR-mediated innate immune signalling pathways involving the EDS1 family proteins and RNLs.

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Section: Products Of the Nad + -Cleavage Reaction Are Required For Downstream Immune Signallingmentioning

confidence: 99%

Structural basis of NLR activation and innate immune signalling in plants

et al. 2022

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“…v2-cADPR (3’cADPR) is also produced by the Pseudomonas syringae DC3000 TIR-domain effector HopAM1 ( 33 ). To examine HopAM1’s ability to suppress immunity, we generated transgenic Arabidopsis plants that express HopAM1 and the catalytically-null mutant HopAM1 E191A .…”

Section: Resultsmentioning

confidence: 99%

“…Bacterial TIR domains have also been found to be capable of cleaving NAD + (22,27,(32)(33)(34), again producing Nam and ADPR or the distinct cADPR isomers v-cADPR or v2-cADPR. In bacteria, NADase activity by TIR domains has recently been found to be a critical component of STING cyclic dinucleotide sensing (22) and the Thoeris defence system (21).…”

Section: Main Textmentioning

confidence: 99%

“…Upon phage infection, ThsB cleaves NAD + and produces a cADPR isomer, which activates ThsA ( 34 ), causing further NAD + depletion and cell death. A bacterial TIR-domain effector protein from Pseudomonas syringae DC3000, HopAM1, has further been shown recently to suppress plant immunity, by producing v2-cADPR ( 33 ). Although cADPR isomers have important immune and virulence functions, neither their chemical structures nor their specific mechanisms of action have been elucidated.…”

Section: Main Textmentioning

confidence: 99%

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Chemical structures of cyclic ADP ribose (cADPR) isomers and the molecular basis of their production and signaling

Manik

Shi

et al. 2022

Preprint

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Cyclic ADP ribose (cADPR) isomers are important signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via NAD+ hydrolysis, yet their chemical structures are unknown. We show that v-cADPR (2’cADPR) and v2-cADPR (3’cADPR) isomers are cyclized by O-glycosidic bond formation between the ribose moieties in ADPR. Structures of v-cADPR (2’cADPR)-producing TIR domains reveal that conformational changes are required for the formation of the active assembly that resembles those of Toll-like receptor adaptor TIR domains, and mutagenesis data demonstrate that a conserved tryptophan is essential for cyclization. We show that v2-cADPR (3’cADPR) is a potent activator of ThsA effector proteins from Thoeris anti-phage defence systems and is responsible for suppression of plant immunity by the effector HopAM1. Collectively, our results define new enzymatic activities of TIR domains, reveal the molecular basis of cADPR isomer production, and establish v2-cADPR (3’cADPR) as an antiviral signaling molecule and an effector-mediated signaling molecule for plant immunity suppression.One-Sentence SummaryThe chemical structures of two O-glycosidic bond-containing cyclic ADP ribose isomers, the molecular basis of their production, and their function in antiviral and plant immunity suppression by bacteria are reported.

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“…On the other, if the TIR‐domain‐generated molecules (in)directly promote calcium fluxes, their roles may be more nuanced, since v‐cADPR‐like molecules do accumulate in plant tissues from TIR domain activity but are insufficient to induce cell death (Bayless & Nishimura, 2020). Furthermore, phytobacterial TIR domain effectors exist that generate v‐cADPR‐like molecules to promote virulence (Eastman et al ., 2022). Superimposed over these findings is the additional question of whether plant calcium homeostasis mechanisms (through channels/pumps/exchangers) are engaged to counter the CNL/RNL‐mediated or cADPR/cAMP/cGMP‐induced calcium fluxes.…”

Section: Figmentioning

confidence: 99%

An epiphany for plant resistance proteins and its impact on calcium‐based immune signalling

Lee

Romeis

2022

New Phytologist

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Flor first postulated the gene-for-gene hypothesis in 1942, which states that 'for each (Resistance, R) gene that conditions reaction in the host there is a corresponding (Avirulence, avr) gene in the parasite that conditions pathogenicity' (Flor, 1971). This is, in fact, the so-called effector-triggered immunity (ETI) described in the 'Zig-Zag model ' (proposed in 2006), which describes alternating phases of immunity during the attempted infection of plants (Ngou et al., 2022). The initial phase, pattern-triggered immunity (PTI), is activated after the sensing of conserved 'patterns' (typically of microbial origin, but they can also be secondary plant-derived signals from damaged tissues) at the cell surface by membrane-localized pattern recognition receptors (PRRs). Adapted pathogens secrete PTI-dampening effector molecules to infect plants, but during evolution, resistant plants may acquire effector detection mechanisms that ultimately lead to ETI, a defence response of higher amplitude than PTI. Retrospectively, Flor's avirulence factors are the effectors secreted by pathogens, but they (or their effects) can be counteracted by R proteins. Understandably, breeders have been keen to identify R genes and develop them to generate disease resistant crops. Starting with the first in 1992, hundreds of R genes have now been cloned, the majority of which encode proteins with conserved structural motifs, termed nucleotide-binding leucine-rich repeat receptors (NLRs). These are further subdivided into CNLs or TNLs that possess either an N-terminal coiled-coil (CC) or a Toll-Interleukin-1 Receptor (TIR) domain, respectively (Kourelis & van der Hoorn, 2018). CNLs are functionally self-sufficient for immune signalling, while TNLs require a special class of 'helper' CNLs called RNLs (due to their CC domain being first described in the R protein RPW8). Furthermore, studies have shown that genes for the membrane-associated protein NDR1 (Non race-specific Disease Resistance 1) and the lipase-like protein EDS1 (Enhanced Disease Susceptibility 1) are required for immune signalling by CNLs and TNLs, respectively (Ngou et al., 2022). However, our understanding of the molecular mechanisms relating to these NLR proteins has been limited. In this issue of New Phytologist, Kim et al. (2022; pp. 813-818) and Parker et al. (2022; pp. 819-826) review recent progress that has completely transformed our understanding of NLR biochemistryboth CNLs and TNLs ultimately converge on generating calcium-permeable pores in plant membranes. Hence, one can anticipate that calcium-based signalling will lead the next 'wave' of insights into signal transduction from plant resistance proteins.

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A phytobacterial TIR domain effector manipulates NAD⁺ to promote virulence

Cited by 54 publications

References 82 publications

Structural basis of NLR activation and innate immune signalling in plants

Structural basis of NLR activation and innate immune signalling in plants

Chemical structures of cyclic ADP ribose (cADPR) isomers and the molecular basis of their production and signaling

An epiphany for plant resistance proteins and its impact on calcium‐based immune signalling

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A phytobacterial TIR domain effector manipulates NAD+ to promote virulence

Cited by 54 publications

References 82 publications

Structural basis of NLR activation and innate immune signalling in plants

Structural basis of NLR activation and innate immune signalling in plants

Chemical structures of cyclic ADP ribose (cADPR) isomers and the molecular basis of their production and signaling

An epiphany for plant resistance proteins and its impact on calcium‐based immune signalling

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A phytobacterial TIR domain effector manipulates NAD⁺ to promote virulence