CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers

Wimmer, Franziska; Beisel, Chase L.

doi:10.3389/fmicb.2019.03078

Cited by 77 publications

(63 citation statements)

References 163 publications

(268 reference statements)

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“…Ubiquitous serovars like Typhimurium, Newport-II, Tennessee, and Heidelberg have huge spacer set while host-specific/adapted serovars like Typhi, Sendai, Gallinarum, Dublin possess a few spacers. Considering the role of spacers in regulating endogenous genes 46 and preventing invading MGE 16 we put forward two possible hypotheses. The spacer versatility in broad-host-range serovars can be due to the exposure to a wide range of environments and/or it permits regulation of different genes.…”

Section: Discussionmentioning

confidence: 99%

The phylogenomics of CRISPR-Cas system and revelation of its features in Salmonella

Kushwaha

Bhavesh

Abdella

et al. 2020

Sci Rep

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Salmonellae display intricate evolutionary patterns comprising over 2500 serovars having diverse pathogenic profiles. The acquisition and/or exchange of various virulence factors influences the evolutionary framework. To gain insights into evolution of Salmonella in association with the CRISPR-Cas genes we performed phylogenetic surveillance across strains of 22 Salmonella serovars. The strains differed in their CRISPR1-leader and cas operon features assorting into two main clades, CRISPR1-STY/cas-STY and CRISPR1-STM/cas-STM, comprising majorly typhoidal and non-typhoidal Salmonella serovars respectively. Serovars of these two clades displayed better relatedness, concerning CRISPR1-leader and cas operon, across genera than between themselves. This signifies the acquisition of CRISPR1/Cas region could be through a horizontal gene transfer event owing to the presence of mobile genetic elements flanking CRISPR1 array. Comparison of CRISPR and cas phenograms with that of multilocus sequence typing (MLST) suggests differential evolution of CRISPR/Cas system. As opposed to broad-host-range, the host-specific serovars harbor fewer spacers. Mapping of protospacer sources suggested a partial correlation of spacer content with habitat diversity of the serovars. Some serovars like serovar Enteritidis and Typhimurium that inhabit similar environment/infect similar hosts hardly shared their protospacer sources.

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Section: Discussionmentioning

confidence: 99%

The phylogenomics of CRISPR-Cas system and revelation of its features in Salmonella

Kushwaha

Bhavesh

Abdella

et al. 2020

Sci Rep

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“…Accidental acquisition of spacers from the cellular genome during adaptation has been reported by several studies with different CRISPR-Cas systems and different organisms showing that this is not a rare phenomenon ( 17 , 19 – 21 ). However, the resulting interference reaction against chromosomal DNA is usually highly toxic ( 22 – 25 ).…”

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confidence: 99%

Adaptation induced by self-targeting in a type I-B CRISPR-Cas system

Stachler

Wörtz

Alkhnbashi

et al. 2020

Journal of Biological Chemistry

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Haloferax volcanii is to our knowledge the only prokaryote known to tolerate CRISPR-Cas mediated damage to its genome in the wild type background; the resulting cleavage of the genome is repaired by homologous recombination restoring the wild type version. In mutant Haloferax strains with enhanced self-targeting, cell fitness decreases and microhomology-mediated end joining becomes active, generating deletions in the targeted gene. Here we use self-targeting to investigate adaptation in H. volcanii CRISPR-Cas type I-B. We show that self-targeting and genome breakage events that are induced by self-targeting, such as those catalysed by active transposases, can generate DNA fragments that are used by the CRISPR-Cas adaptation machinery for integration into the CRISPR loci. Low cellular concentrations of self-targeting crRNAs resulted in acquisition of large numbers of spacers originating from the entire genomic DNA. In contrast, high concentrations of self-targeting crRNAs resulted in lower acquisition that was mostly centred around the targeting site. Furthermore, we observed naïve spacer acquisition at a low level in wild type Haloferax cells and with higher efficiency upon overexpression of the Cas proteins Cas1, Cas2 and Cas4. Taken together these findings indicate that naïve adaptation is a regulated process in H. volcanii that operates at low basal levels and is induced by DNA breaks.

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“…possess a few spacers. Considering the role of spacers in regulating endogenous genes 32 , we hypothesize that versatility in spacers opens up opportunities to infect multiple hosts permitting the regulation of a variety of genes. All the spacers of the host-specific serovars Gallinarum, Pullorum, and Gallinarum/Pullorum are present in serovar Enteritidis (a broad-host-range serovar) along with some additional spacers further testifying our hypothesis.…”

Section: Discussionmentioning

confidence: 99%

The Phylogenomics of CRISPR-Cas System inSalmonella: an evolutionary race with housekeeping genes

Kushwaha¹,

Lahiri

Abdella

et al. 2020

Preprint

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AbstractSalmonellae display intricate evolutionary patterns comprising over 2500 serovars having diverse pathogenic profiles. The acquisition/exchange of various virulence factors influence the evolutionary framework. To gain insights into evolution of Salmonella as a pathogen in association with the CRISPR-Cas genes we performed phylogenetic surveillance across strains of 22 Salmonella serovars. The strains assorted into two main clades, pertaining to the differences in their CRISPR1-leader and cas operon. Considering Salmonella enterica subsp. enterica serovar Typhimurium and serovar Typhi as signature serovars, we classified the clades as CRISPR1-STM/cas-STM and CRISPR1-STY/cas-STY, respectively. Serovars of the two clades displayed better relatedness, concerning CRISPR-1 leader and cas operon, across genera than between themselves. This signifies the acquisition of CRISPR1/Cas region a horizontal gene transfer event owing to the presence of mobile genetic elements flanking CRISPR1 array. The CRISPR2 tree does not show such relation. Spacer mapping of the two CRISPR arrays suggests the construct to be canonical, with only 8.8% spacer conservation among the serovars. As opposed to broad-host-range serovars, the host-specific serovars harbor fewer spacers. All typhoidal serovars have CRISPR1-STY/cas-STY system. Comparison of CRISPR and cas phenograms with that of multilocus sequence typing (MLST) suggests differential evolution of CRISPR/Cas system implying supplementary roles beyond immunity.

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CRISPR-Cas Systems and the Paradox of Self-Targeting Spacers

Cited by 77 publications

References 163 publications

The phylogenomics of CRISPR-Cas system and revelation of its features in Salmonella

The phylogenomics of CRISPR-Cas system and revelation of its features in Salmonella

Adaptation induced by self-targeting in a type I-B CRISPR-Cas system

The Phylogenomics of CRISPR-Cas System inSalmonella: an evolutionary race with housekeeping genes

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