DdmABC-dependent death triggered by viral palindromic DNA sequences
William P Robins1, Bradley T Meader1, Jonida Toska1
1Department of Microbiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Abstract:
Defense systems that recognize viruses provide important insights into both prokaryotic and eukaryotic innate immunity mechanisms. Such systems that restrict foreign DNA or trigger cell death have recently been recognized, but the molecular signals that activate many of these remain largely unknown. Here, we characterize one such system in pandemic Vibrio cholerae responsible for triggering cell density-dependent death (CDD) of cells in response to the presence of certain genetic elements. We show that the key component is the Lamassu DdmABC anti-phage/plasmid defense system. We demonstrate that signals that trigger CDD were palindromic DNA sequences in phages and plasmids that are predicted to form stem-loop hairpins from single-stranded DNA. Our results suggest that agents that damage DNA also trigger DdmABC activation and inhibit cell growth. Thus, any infectious process that results in damaged DNA, particularly during DNA replication, can in theory trigger DNA restriction and death through the DdmABC abortive infection system.
Insights
Researchers identified the Lamassu DdmABC system in Vibrio cholerae, which triggers cell death upon detecting viral DNA. This defense mechanism activates when foreign DNA forms stem-loop structures, offering insights into bacterial immunity.
Area of Science:
- Microbiology
- Bacterial genetics
- Innate immunity
Background:
- Prokaryotic and eukaryotic innate immunity mechanisms are crucial for defense against pathogens.
- Molecular signals activating many defense systems, particularly those involving cell death, remain largely uncharacterized.
- Vibrio cholerae possesses defense systems that respond to foreign genetic elements.
Purpose of the Study:
- To characterize a cell density-dependent death (CDD) system in Vibrio cholerae.
- To identify the molecular signals that activate this defense system.
- To elucidate the role of the Lamassu DdmABC system in bacterial defense.
Main Methods:
- Genetic analysis of Vibrio cholerae strains.
- DNA sequence analysis to identify trigger motifs.
- Experimental validation of DNA structures and their effect on CDD.
Main Results:
- The Lamassu DdmABC system is identified as the key component responsible for CDD.
- Palindromic DNA sequences forming stem-loop hairpins in phages and plasmids trigger CDD.
- DNA-damaging agents also activate DdmABC, inhibiting cell growth.
Conclusions:
- The DdmABC system acts as an anti-phage and anti-plasmid defense mechanism in Vibrio cholerae.
- Foreign DNA structures, specifically stem-loop hairpins, are identified as potent activators.
- This abortive infection system can be triggered by DNA damage during infection or replication, leading to cell death.
More Related Videos
Related Concept Videos
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:17The Extrinsic Apoptotic Pathway
02:23Abnormal Proliferation
02:37DNA Damage can Stall the Cell Cycle
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:31The Intrinsic Apoptotic Pathway