Conquering CRISPR: how phages overcome bacterial adaptive immunity

Malone, Lucia M; Birkholz, Nils; Fineran, Peter C.

doi:10.1016/j.copbio.2020.09.008

Cited by 63 publications

(48 citation statements)

References 78 publications

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“…The selective pressure of CRISPR–Cas systems has led to the evolution of phage-encoded anti-defence strategies, such as anti-CRISPRs ( 70 , 71 ). We hypothesised that, since RsmA represses CRISPR–Cas systems, mobile genetic elements may exploit this by encoding similar proteins.…”

Section: Resultsmentioning

confidence: 99%

“…In fact, csrA was engineered into an M13 filamentous phage, which led to manipulation of biofilm and antibiotic sensitivity properties of E. coli ( 86 ). Our work adds to the concept that regulatory proteins in phage genomes may have anti-CRISPR activity ( 71 ). Indeed, a regulator of alginate biosynthesis in P. aeruginosa was recently shown to be encoded by some phages and repress CRISPR–Cas expression ( 87 ).…”

Section: Discussionmentioning

confidence: 98%

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The Rsm (Csr) post-transcriptional regulatory pathway coordinately controls multiple CRISPR–Cas immune systems

Campa

Smith

Hampton

et al. 2021

Nucleic Acids Research

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CRISPR–Cas systems provide bacteria with adaptive immunity against phages and plasmids; however, pathways regulating their activity are not well defined. We recently developed a high-throughput genome-wide method (SorTn-seq) and used this to uncover CRISPR–Cas regulators. Here, we demonstrate that the widespread Rsm/Csr pathway regulates the expression of multiple CRISPR–Cas systems in Serratia (type I-E, I-F and III-A). The main pathway component, RsmA (CsrA), is an RNA-binding post-transcriptional regulator of carbon utilisation, virulence and motility. RsmA binds cas mRNAs and suppresses type I and III CRISPR–Cas interference in addition to adaptation by type I systems. Coregulation of CRISPR–Cas and flagella by the Rsm pathway allows modulation of adaptive immunity when changes in receptor availability would alter susceptibility to flagella-tropic phages. Furthermore, we show that Rsm controls CRISPR–Cas in other genera, suggesting conservation of this regulatory strategy. Finally, we identify genes encoding RsmA homologues in phages, which have the potential to manipulate the physiology of host bacteria and might provide an anti-CRISPR activity.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

The Rsm (Csr) post-transcriptional regulatory pathway coordinately controls multiple CRISPR–Cas immune systems

Campa

Smith

Hampton

et al. 2021

Nucleic Acids Research

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“…As mentioned previously, a pivotal function of modifications in phage genomes is thought to be prevention of cleavage by host restriction endonucleases [ 4 , 5 , 6 , 7 ]. Indeed, bacteriophage gDNAs containing modified nucleotides are partially or completely resistant to cleavage by a variety of REases in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Over years of evolution, bacteria have developed mechanisms of defending themselves from phages, such as the use of CRISPR-Cas and restriction-modification systems [ 2 , 3 ]. On the other hand, phages have evolved counter measures to escape these defenses, and one of the most widespread strategies is to modify their DNA [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Pantoea Bacteriophage vB_PagS_MED16—A Siphovirus Containing a 2′-Deoxy-7-amido-7-deazaguanosine-Modified DNA

Šimoliūnienė

Žukauskienė

Truncaitė

et al. 2021

IJMS

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A novel siphovirus, vB_PagS_MED16 (MED16) was isolated in Lithuania using Pantoea agglomerans strain BSL for the phage propagation. The double-stranded DNA genome of MED16 (46,103 bp) contains 73 predicted open reading frames (ORFs) encoding proteins, but no tRNA. Our comparative sequence analysis revealed that 26 of these ORFs code for unique proteins that have no reliable identity when compared to database entries. Based on phylogenetic analysis, MED16 represents a new genus with siphovirus morphology. In total, 35 MED16 ORFs were given a putative functional annotation, including those coding for the proteins responsible for virion morphogenesis, phage–host interactions, and DNA metabolism. In addition, a gene encoding a preQ0 DNA deoxyribosyltransferase (DpdA) is present in the genome of MED16 and the LC–MS/MS analysis indicates 2′-deoxy-7-amido-7-deazaguanosine (dADG)-modified phage DNA, which, to our knowledge, has never been experimentally validated in genomes of Pantoea phages. Thus, the data presented in this study provide new information on Pantoea-infecting viruses and offer novel insights into the diversity of DNA modifications in bacteriophages.

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“…Among the many protection strategies employed against these invaders, the highly diverse CRISPR-Cas systems stand out as the only known adaptive immune systems in bacteria ( Hampton et al, 2020 ). In response, phages and MGEs have evolved a large array of anti-CRISPR (Acr) proteins which can inhibit CRISPR-Cas defense through various means ( Malone et al, 2021 , Wiegand et al, 2020 ). With different Cas proteins, such as Cas9, being utilized as tools in bioengineering, Acr proteins offer a way to make these tools more controllable and may substantially facilitate their application ( Marino et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%