Prophages are associated with extensive CRISPR-Cas auto-immunity.

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• CRISPR-Cas systems are crucial for bacterial adaptive immunity, distinguishing self from non-self DNA.
• Self-targeting spacers (STS), which target the bacterium's own genome, have been observed but their prevalence and implications are unclear.

Purpose of the Study:

• To investigate the incidence, distribution, and evasion mechanisms of self-targeting spacers (STS) across a large dataset of bacterial genomes.
• To understand the relationship between STS, prophages, and potential autoimmunity in bacteria.

Main Methods:

• Bioinformatic analysis of over 100,000 bacterial genomes.
• Identification and characterization of CRISPR-Cas systems and self-targeting spacers (STS).
• Mapping of STS to genomic regions, including prophages.

Main Results:

• Self-targeting spacers (STS) were found in one-fifth of CRISPR-carrying bacteria across all CRISPR-Cas types, with high prevalence in types I-B and I-F.
• STS-containing genomes frequently harbor prophages, with STS often mapping to these regions.
• Mechanisms like anti-CRISPR proteins and target mutations appear to mitigate the potentially detrimental effects of STS.

Conclusions:

• Self-targeting spacers (STS) are common in bacteria and frequently target prophages, suggesting a role in managing phage infections.
• Primed spacer acquisition may lead to increased STS in type I systems without causing autoimmunity.
• Bacteria possess robust evasion mechanisms that confer tolerance to STS-targeted prophages, preventing self-destruction.