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Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
Published on: May 8, 2013
Manganese activates the CBASS immunity to protect bacteria from phage infection
Xiao Wang1, Yongdong Li2, Xiao Wang1
1State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China.
Abstract:
The cyclic-oligonucleotide-based antiphage signaling system (CBASS) is essential for bacterial defense against phage infections, mirroring many features of the eukaryotic cGAS-STING pathway. Although metal ions are well-known regulators of cGAS-STING activation, their impact on CBASS-mediated antiviral function remains largely unexplored. Here, we show that manganese (Mn2+) serves as a key cofactor to enhance CBASS activation. Upon phage infection, the intracellular Mn2+ level is elevated, and the gene expression of the Mn2+ transportation system is upregulated. We found that Mn2+ directly augments the activity of DncV, markedly boosting 3'3'-cGAMP production. Consequently, the phospholipase CapV is activated more rapidly, driving premature bacterial cell lysis and curtailing phage replication. Notably, Mn2+ also alleviates folate-mediated inhibition of DncV, underscoring its role as a potent modulator of cyclic dinucleotide signaling. Our findings reveal a mechanism through which Mn2+ confers bacterial resistance to phages, mirroring the Mn2+-enhanced antiviral responses of mammalian cGAS-STING.
Importance:
Bacteriophages pose a persistent threat to bacterial survival, driving the evolution of diverse antiviral systems, including the cyclic-oligonucleotide-based antiphage signaling system (CBASS) immunity. Here, we reveal that manganese (Mn2+) acts as a pivotal cofactor for CBASS, directly enhancing the activity of the cGAS-like cyclase DncV to generate 3'3'-cGAMP, which, in turn, activates the phospholipase CapV. This Mn2+-driven DncV activation induces rapid bacterial cell death, thereby limiting phage replication. These findings underscore a striking parallel with mammalian cGAS-STING, where Mn2+ likewise amplifies antiviral responses. By illuminating the importance of Mn2+ homeostasis in bacterial phage resistance, our study broadens the understanding of bacterial innate immunity and highlights a deeply conserved mechanism across prokaryotes and eukaryotes.
Insights
Manganese (Mn2+) enhances bacterial defense against phages by boosting the cyclic-oligonucleotide-based antiphage signaling system (CBASS). This cofactor boosts DncV activity, leading to rapid cell lysis and reduced phage replication, mirroring mammalian antiviral responses.
Area of Science:
- Bacterial innate immunity
- Molecular mechanisms of antiviral defense
- Prokaryotic and eukaryotic signaling pathways
Background:
- Bacteriophages are a constant threat to bacteria, necessitating robust defense systems like the cyclic-oligonucleotide-based antiphage signaling system (CBASS).
- The role of metal ions, particularly manganese (Mn2+), in modulating CBASS activity and bacterial antiviral defense is largely unknown, despite their known influence on related eukaryotic pathways like cGAS-STING.
Purpose of the Study:
- To investigate the role of manganese (Mn2+) as a cofactor in the bacterial cyclic-oligonucleotide-based antiphage signaling system (CBASS).
- To elucidate the mechanism by which Mn2+ enhances CBASS-mediated antiviral activity and bacterial resistance to phage infection.
Main Methods:
- Investigated the effect of Mn2+ on the activity of the DncV cyclase and its production of 3'3'-cGAMP.
- Assessed the impact of Mn2+-enhanced CBASS signaling on the activation of the phospholipase CapV and subsequent bacterial cell lysis.
- Examined changes in intracellular Mn2+ levels and Mn2+ transporter gene expression during phage infection.
Main Results:
- Manganese (Mn2+) directly augments the activity of the DncV cyclase, significantly increasing 3'3'-cGAMP production.
- Elevated intracellular Mn2+ levels during phage infection accelerate CapV activation, leading to premature bacterial cell lysis and reduced phage replication.
- Mn2+ alleviates folate-mediated inhibition of DncV, highlighting its role in regulating cyclic dinucleotide signaling and bacterial antiviral defense.
Conclusions:
- Manganese (Mn2+) is a critical cofactor for CBASS activation, enhancing bacterial resistance to phage infection through a conserved mechanism similar to mammalian cGAS-STING.
- The study reveals a novel aspect of bacterial innate immunity, emphasizing the importance of Mn2+ homeostasis in combating viral threats.
- Findings provide a deeper understanding of the interplay between metal ions and cyclic dinucleotide signaling in prokaryotic antiviral defense.
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