Discovery of multiple anti-CRISPRs uncovers anti-defense gene clustering in mobile genetic elements

Pinilla‐Redondo, Rafael; Shehreen, Saadlee; Marino, Nicole D.; Fagerlund, Robert D.; Brown, Chris M.; Soerensen, S. J.; Fineran, Peter C.; Bondy‐Denomy, Joseph

doi:10.1101/2020.05.22.110304

Cited by 6 publications

(5 citation statements)

References 90 publications

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“…Future work will be required to test these candidates against relevant systems in the species of interest. Lastly, some of these candidate Acr proteins might inhibit other, non-CRISPR-based bacterial immune systems, given that, as recently shown, anti-defense genes show a strong tendency to cluster in MGEs 42 . The signatures of Acrs described in this work might apply broadly to inhibitors of other prokaryotic immune systems.…”

Section: Discussionmentioning

confidence: 92%

Machine-learning approach expands the repertoire of anti-CRISPR protein families

et al. 2020

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The CRISPR-Cas are adaptive bacterial and archaeal immunity systems that have been harnessed for the development of powerful genome editing and engineering tools. In the incessant host-parasite arms race, viruses evolved multiple anti-defense mechanisms including diverse anti-CRISPR proteins (Acrs) that specifically inhibit CRISPR-Cas and therefore have enormous potential for application as modulators of genome editing tools. Most Acrs are small and highly variable proteins which makes their bioinformatic prediction a formidable task. We present a machine-learning approach for comprehensive Acr prediction. The model shows high predictive power when tested against an unseen test set and was employed to predict 2,500 candidate Acr families. Experimental validation of top candidates revealed two unknown Acrs (AcrIC9, IC10) and three other top candidates were coincidentally identified and found to possess anti-CRISPR activity. These results substantially expand the repertoire of predicted Acrs and provide a resource for experimental Acr discovery.

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Section: Discussionmentioning

confidence: 92%

Machine-learning approach expands the repertoire of anti-CRISPR protein families

et al. 2020

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“…Defense systems, such as CRISPR-Cas systems ( 1 ), restriction modification systems ( 2 ), and other anti-phage systems are frequently encoded on MGEs (termed ‘defense islands’) ( 3 ) and are thus able to mobilize and spread. These defense systems and the genes they encode can protect a bacterial host from infecting phages, or conversely be co-opted by phages, allowing infecting phages to overcome bacterial host defenses ( 4 , 5 ). In addition to facilitating mobilization, MGEs are a major driver of the evolutionary adaptation of defense genes and systems.…”

Section: Introductionmentioning

confidence: 99%

A phage satellite tunes inducing phage gene expression using a domesticated endonuclease to balance inhibition and virion hijacking

Netter

Boyd

Silvas

et al. 2021

Nucleic Acids Research

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Bacteria persist under constant threat of predation by bacterial viruses (phages). Bacteria-phage conflicts result in evolutionary arms races often driven by mobile genetic elements (MGEs). One such MGE, a phage satellite in Vibrio cholerae called PLE, provides specific and robust defense against a pervasive lytic phage, ICP1. The interplay between PLE and ICP1 has revealed strategies for molecular parasitism allowing PLE to hijack ICP1 processes in order to mobilize. Here, we describe the mechanism of PLE-mediated transcriptional manipulation of ICP1 structural gene transcription. PLE encodes a novel DNA binding protein, CapR, that represses ICP1’s capsid morphogenesis operon. Although CapR is sufficient for the degree of capsid repression achieved by PLE, its activity does not hinder the ICP1 lifecycle. We explore the consequences of repression of this operon, demonstrating that more stringent repression achieved through CRISPRi restricts both ICP1 and PLE. We also discover that PLE transduces in modified ICP1-like particles. Examination of CapR homologs led to the identification of a suite of ICP1-encoded homing endonucleases, providing a putative origin for the satellite-encoded repressor. This work unveils a facet of the delicate balance of satellite-mediated inhibition aimed at blocking phage production while successfully mobilizing in a phage-derived particle.

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“…Then, we compared the prevalence of Acr in species in which the presence of CRISPR-Cas is positively or negatively correlated with the MGE content, separately considering genomes that do and do not harbor CRISPR-Cas. Because Acr are generally encoded by MGE (29) and the prevalence of MGE systematically varies across groups acting as a confounding factor, we restricted our comparisons to genomes that contain at least one prophage. Our results indicate that genomes with and without CRISPR-Cas differ in the prevalence of Acr (Fig.…”

Section: Anti-crispr Proteins Modulate Associations Between Crispr-ca...mentioning

confidence: 99%

“…The copyright holder for this preprint this version posted February 29, 2024. ; https://doi.org/10.1101/2024.02. 29.582795 doi: bioRxiv preprint At odds with the naïve expectation that defense systems should reduce the rates of HGT by interfering with the propagation of MGE, several empirical and theoretical observations suggest that the relation between defense systems and HGT might be more complex. First, the selection pressure to maintain defense systems in a population (and consequently their prevalence) generally increases with the exposure to MGE (22).…”

Section: Introductionmentioning

confidence: 99%

Timescale and genetic linkage explain the variable impact of defense systems on horizontal gene transfer

Liu,

Botelho,

Iranzo

2024

Preprint

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Prokaryotes have evolved a wide repertoire of defense systems to prevent invasion by mobile genetic elements (MGE). However, because MGE are vehicles for the exchange of beneficial accessory genes, defense systems could consequently impede rapid adaptation in microbial populations. Here, we study how defense systems impact horizontal gene transfer (HGT) in the short and long terms. By combining comparative genomics and phylogeny-aware statistical methods, we quantified the association between the presence of 7 widespread defense systems and the abundance of MGE in the genomes of 196 bacterial and 1 archaeal species. We also calculated the differences in the rates of gene gain and loss between lineages that possess and lack each defense system. Our results show that the impact of defense systems on HGT is highly species- and system-dependent. CRISPR-Cas stands out as the defense system that most often associates with a decrease in the number of MGE and reduced gene acquisition. Timescale analysis reveals that defense systems must persist in a lineage for a relatively long time in order exert an appreciable negative impact on HGT. In contrast, at short evolutionary times, defense systems, MGE, and gene gain rates tend to be positively correlated. Based on these results and given the high turnover rates experienced by defense systems, we propose that the inhibitory effect of most defense systems on HGT is masked by recent co-transfer events involving MGE.

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Discovery of multiple anti-CRISPRs uncovers anti-defense gene clustering in mobile genetic elements

Cited by 6 publications

References 90 publications

Machine-learning approach expands the repertoire of anti-CRISPR protein families

Machine-learning approach expands the repertoire of anti-CRISPR protein families

A phage satellite tunes inducing phage gene expression using a domesticated endonuclease to balance inhibition and virion hijacking

Timescale and genetic linkage explain the variable impact of defense systems on horizontal gene transfer

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