The pan-immune system of bacteria: antiviral defence as a community resource

Bernheim, Aude; Sorek, Rotem

doi:10.1038/s41579-019-0278-2

Cited by 507 publications

(426 citation statements)

References 92 publications

Supporting

Mentioning

407

Contrasting

Unclassified

Order By: Relevance

“…Altogether, these results indicate that once the Ec48 retron defense system senses the presence of phage-encoded RecBCD inhibitors, it causes cell death. This form of protection against phage infection is called abortive infection (Abi), and is a common defensive strategy employed by multiple, mechanistically diverse bacterial immune systems 35 . Representative phage mutants capable of escaping Ec48 retron system defense.…”

Section: Figure 1 a Retron-containing Genetic System Protects Againsmentioning

confidence: 99%

Bacterial retrons function in anti-phage defense

Millman

Bernheim

Stokar-Avihail

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Retrons are bacterial genetic elements comprised of a reverse transcriptase (RT) and a non-coding RNA. The RT uses the non-coding RNA as a template, generating a chimeric RNA/DNA molecule in which the RNA and DNA components are covalently linked. Although retrons were discovered three decades ago, their function remained unknown. In this study we report that retrons function as anti-phage defense systems. The defensive unit is composed of three components: the RT, the non-coding RNA, and an effector protein. Retron-containing systems are abundant in genomic "defense islands", suggesting a role for most retrons in phage resistance. By cloning multiple retron systems into a retron-less Escherichia coli strain, we show that these systems confer defense against a broad range of phages, with different retrons defending against different phages. Focusing on a single retron, Ec48, we show evidence that it is a "guardian" of RecBCD, a complex with central anti-phage functions in the bacterial cell. Inhibition of RecBCD by dedicated phage proteins activates the retron, leading to abortive infection and cell death. Thus, the Ec48 retron forms a second line of defense that is triggered if the first lines of defense have collapsed. Our results expose a new family of anti-phage defense systems abundant in bacteria.

show abstract

Section: Figure 1 a Retron-containing Genetic System Protects Againsmentioning

confidence: 99%

Bacterial retrons function in anti-phage defense

Millman

Bernheim

Stokar-Avihail

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Bacterial sensitivity/resistance to phages is typically characterized using phenotypic methods such as cross-infection patterns against a panel of phages [14][15][16][17][18][19][20][21][22][23][24][25][26][27] or by whole-genome sequencing of phage-resistant mutants [28][29][30][31][32]. As such, our understanding of bacterial resistance mechanisms against phages remains limited, and the field is therefore in need of improved methods to characterize phage-host interactions, determine the generality and diversity of phage resistance mechanisms in nature, and identify the degree of specificity for each bacterial resistance mechanism across diverse phage types [13,25,26,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47].…”

Section: Introductionmentioning

confidence: 99%

High-throughput mapping of the phage resistance landscape inE. coli

Mutalik¹,

Adler²,

Rishi³

et al. 2020

Preprint

View full text Add to dashboard Cite

Bacteriophages (phages) are critical players in the dynamics and function of microbial communities and drive processes as diverse as global biogeochemical cycles and human health. Phages tend to be predators finely tuned to attack specific hosts, even down to the strain level, which in turn defend themselves using an array of mechanisms. However, to date, efforts to rapidly and comprehensively identify bacterial host factors important in phage infection and resistance have yet to be fully realized. Here, we globally map the host genetic determinants involved in resistance to 14 phylogenetically diverse double-stranded DNA phages using two model Escherichia coli strains (K-12 and BL21) with known sequence divergence to demonstrate strain-specific differences. Using genome-wide loss-of-function and gain-of-function genetic technologies, we are able to confirm previously described phage receptors as well as uncover a number of previously unknown host factors that confer resistance to one or more of these phages. We uncover differences in resistance factors that strongly align with the susceptibility of K-12 and BL21 to specific phage. We also identify both phage specific mechanisms, such as the unexpected role of cyclic-di-GMP in host sensitivity to phage N4, and more generic defenses, such as the overproduction of colanic acid capsular polysaccharide that defends against a wide array of phages. Our results indicate that host responses to phages can occur via diverse cellular mechanisms. Our systematic and highthroughput genetic workflow to characterize phage-host interaction determinants can be extended to diverse bacteria to generate datasets that allow predictive models of how phagemediated selection will shape bacterial phenotype and evolution. The results of this study and future efforts to map the phage resistance landscape will lead to new insights into the coevolution of hosts and their phage, which can ultimately be used to design better phage therapeutic treatments and tools for precision microbiome engineering.3 Introduction:

show abstract

“…We found that the gene neighborhoods of loci encoding Acr and Anti-RM proteins are typically crowded with other small hypothetical protein-coding genes of unknown function ( Figure 5). We speculate that these "anti-defense islands" may constitute an unrecognized phenomenon in diverse MGEs, potentially enriched with new genes that antagonize diverse defense systems (Bernheim and Sorek, 2019).…”

Section: Acrs Cluster With Anti-rm and Other Anti-defense Genesmentioning

confidence: 99%

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

Pinilla‐Redondo

Shehreen

Marino

et al. 2020

Preprint

View full text Add to dashboard Cite

Many prokaryotes employ CRISPR-Cas systems to combat invading mobile genetic elements (MGEs). In response, some MGEs have evolved Anti-CRISPR (Acr) proteins to bypass this immunity, yet the diversity, distribution and spectrum of activity of this immune evasion strategy remain largely unknown. Here, we uncover 11 new type I anti-CRISPR genes encoded on numerous chromosomal and extrachromosomal mobile genetic elements within Enterobacteriaceae and Pseudomonas. Candidate genes were identified adjacent to anti-CRISPR associated gene 5 (aca5) and assayed against a panel of six type I systems: I-F (Pseudomonas, Pectobacterium, and Serratia), I-E (Pseudomonas and Serratia), and I-C (Pseudomonas), revealing the type I-F and/or I-E acr genes and a new aca (aca9). We find that acr genes not only associate with other acr genes, but also with inhibitors of distinct bacterial defense systems. These genomic regions appear to be "anti-defense islands", reminiscent of the clustered arrangement of "defense islands" in prokaryotic genomes. Our findings expand on the diversity of CRISPR-Cas inhibitors and reveal the potential exploitation of acr loci neighborhoods for identifying new anti-defense systems.

show abstract

The pan-immune system of bacteria: antiviral defence as a community resource

Cited by 507 publications

References 92 publications

Bacterial retrons function in anti-phage defense

Bacterial retrons function in anti-phage defense

High-throughput mapping of the phage resistance landscape inE. coli

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

Contact Info

Product

Resources

About