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Researchers discovered that bacterial diadenylate cyclase (DAC) enzymes, previously known for regulating cellular processes like osmoregulation, also play specialized roles in anti-phage defense systems. They identified a defense system called Panoptoo, where the DAC protein PanS synthesizes diverse nucleotide signals including 3'3'-cUA and 3'3'-c-di-AMP that regulate an anti-viral effector protein. The system functions as a molecular decoy to detect when phages attempt to evade bacterial immunity by inhibiting nucleotide signals, with structural analysis revealing how the enzyme produces asymmetric signaling molecules through alterations in its active site.
Why it matters
This expands our understanding of bacterial immune systems and could inform the development of new antibacterial strategies or phage therapies. The discovery that bacteria use decoy signaling to counter viral evasion tactics reveals a previously unknown layer of the evolutionary arms race between bacteria and phages.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Bacterial diadenylate cyclase (DAC) enzymes synthesize the nucleotide signal 3’3′ cyclic di-AMP (3’3′-c-di-AMP) to control osmoregulation, cell-wall homeostasis, and DNA-damage responses. Here we discover specialized roles for DAC enzymes in bacterial immunity and define a Panoptes-like system we name Panoptoo as a DAC-containing anti-phage defense that guards against viral immune evasion. The Panoptoo protein PanS is a minimal DAC that constitutively synthesizes 3’3′ cyclic UMP-AMP (3’3′-cUA) or 3’3′-c-di-AMP to negatively regulate a partnering PanE S2TM{beta} membrane-targeting effector. We show that Panoptoo decoy signaling acts as a counter-defense to detect phage immune evasion proteins that inhibit nucleotide immune signals. A 1.5 [A] crystal structure of PanS in complex with 3’3′-cUA explains how a symmetry break in the canonical DAC active site enables synthesis of asymmetric signaling molecules. Together, our results uncover a role for DAC domains in bacterial anti-phage defense and expand our understanding of nucleotide signaling in antiviral immunity.
Source: Bacterial diadenylate cyclase domains synthesize diverse nucleotide signals in anti-phage defense