Recruitment of CRISPR-Cas systems by Tn7-like transposons

A survey of bacterial and archaeal genomes shows that many Tn7-like transposons contain minimal type I-F CRISPR-Cas systems that consist of fused cas8f and cas5f, cas7f, and cas6f genes and a short CRISPR array. Several small groups of Tn7-like transposons encompass similarly truncated type I-B CRISPR-Cas. This minimal gene complement of the transposon-associated CRISPR-Cas systems implies that they are competent for pre-CRISPR RNA (precrRNA) processing yielding mature crRNAs and target binding but not target cleavage that is required for interference. Phylogenetic analysis demonstrates that evolution of the CRISPR-Cas–containing transposons included a single, ancestral capture of a type I-F locus and two independent instances of type I-B loci capture. We show that the transposon-associated CRISPR arrays contain spacers homologous to plasmid and temperate phage sequences and, in some cases, chromosomal sequences adjacent to the transposon. We hypothesize that the transposon-encoded CRISPR-Cas systems generate displacement (R-loops) in the cognate DNA sites, targeting the transposon to these sites and thus facilitating their spread via plasmids and phages. These findings suggest the existence of RNA-guided transposition and fit the guns-for-hire concept whereby mobile genetic elements capture host defense systems and repurpose them for different stages in the life cycle of the element.

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Recruitment of CRISPR-Cas systems by Tn7-like transposons

10.1101/154229 ◽

2017 ◽

Author(s):

Joseph E. Peters ◽

Kira S. Makarova ◽

Sergey Shmakov ◽

Eugene V. Koonin

Keyword(s):

Phylogenetic Analysis ◽

Host Defense ◽

Mobile Genetic Elements ◽

Comparative Genomic ◽

Type I ◽

Genetic Elements ◽

Defense Systems ◽

Crispr Array ◽

Target Binding ◽

Chromosomal Sequences

AbstractA survey of bacterial and archaeal genomes shows that many Tn7-like transposons contain ‘minimal’ type I-F CRISPR-Cas systems that consist of fused cas8f and cas5f, cas7f and cas6f genes, and a short CRISPR array. Additionally, several small groups of Tn7-like transposons encompass similarly truncated type I-B CRISPR-Cas systems. This gene composition of the transposon-associated CRISPR-Cas systems implies that they are competent for pre-crRNA processing yielding mature crRNAs and target binding but not target cleavage that is required for interference. Here we present phylogenetic analysis demonstrating that evolution of the CRISPR-Cas containing transposons included a single, ancestral capture of a type I-F locus and two independent instances of type I-B loci capture. We further show that the transposon-associated CRISPR arrays contain spacers homologous to plasmid and temperate phage sequences, and in some cases, chromosomal sequences adjacent to the transposon. A hypothesis is proposed that the transposon-encoded CRISPR-Cas systems generate displacement (R-loops) in the cognate DNA sites, targeting the transposon to these sites and thus facilitating their spread via plasmids and phages. This scenario fits the “guns for hire” concept whereby mobile genetic elements can capture host defense systems and repurpose them for different stages in the life cycle of the element.ImportanceCRISPR-Cas is an adaptive immunity system that protects bacteria and archaea from mobile genetic elements. We present comparative genomic and phylogenetic analysis of degenerate CRISPR-Cas variants associated with distinct families of transposable elements and develop the hypothesis that such repurposed defense systems contribute to the transposable element propagation by facilitating transposition into specific sites. Such recruitment of defense systems by mobile elements supports the “guns for hire” concept under which the same enzymatic machineries can be alternately employed for transposon proliferation or host defense.

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The History and Mystery of Alveolar Epithelial Type II Cells: Focus on Their Physiologic and Pathologic Role in Lung

International Journal of Molecular Sciences ◽

10.3390/ijms22052566 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2566 ◽

Cited By ~ 1

Author(s):

Barbara Ruaro ◽

Francesco Salton ◽

Luca Braga ◽

Barbara Wade ◽

Paola Confalonieri ◽

...

Keyword(s):

Host Defense ◽

Defense Mechanisms ◽

Work Of Breathing ◽

Surfactant Proteins ◽

Alveolar Type ◽

Type I ◽

Type Ii ◽

Lung Protection ◽

Alveolar Epithelial ◽

Distal Lung

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air–liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.

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Thromboinflammation as a Driver of Venous Thromboembolism

Hämostaseologie ◽

10.1055/a-1661-0257 ◽

2021 ◽

Vol 41 (06) ◽

pp. 428-432

Author(s):

Nadine Gauchel ◽

Krystin Krauel ◽

Muataz Ali Hamad ◽

Christoph Bode ◽

Daniel Duerschmied

Keyword(s):

Innate Immunity ◽

Venous Thromboembolism ◽

Host Defense ◽

Thrombus Formation ◽

Pathological Process ◽

Defense Systems ◽

Underlying Mechanisms

AbstractThrombus formation has been identified as an integral part in innate immunity, termed immunothrombosis. Activation of host defense systems is known to result in a procoagulant environment. In this system, cellular players as well as soluble mediators interact with each other and their dysregulation can lead to the pathological process of thromboinflammation. These mechanisms have been under intensified investigation during the COVID-19 pandemic. In this review, we focus on the underlying mechanisms leading to thromboinflammation as one trigger of venous thromboembolism.

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The Cross-Regulation Between Autophagy and Type I Interferon Signaling in Host Defense

Advances in Experimental Medicine and Biology - Autophagy Regulation of Innate Immunity ◽

10.1007/978-981-15-0606-2_8 ◽

2019 ◽

pp. 125-144 ◽

Cited By ~ 2

Author(s):

Shouheng Jin

Keyword(s):

Host Defense ◽

Type I Interferon ◽

Type I ◽

Interferon Signaling ◽

The Cross

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Host Defense Systems

10.1007/springerreference_32327 ◽

2011 ◽

Keyword(s):

Host Defense ◽

Defense Systems

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STING signaling and host defense against microbial infection

Experimental & Molecular Medicine ◽

10.1038/s12276-019-0333-0 ◽

2019 ◽

Vol 51 (12) ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Jeonghyun Ahn ◽

Glen N. Barber

Keyword(s):

Host Defense ◽

Innate Immune ◽

Type I Interferons ◽

Type I ◽

Microbial Infection ◽

Immune Signaling ◽

Pathogen Invasion ◽

Innate Immune Signaling ◽

Specific Pathogen ◽

Microbial Dna

AbstractThe first line of host defense against infectious agents involves activation of innate immune signaling pathways that recognize specific pathogen-associated molecular patterns (PAMPs). Key triggers of innate immune signaling are now known to include microbial-specific nucleic acid, which is rapidly detected in the cytosol of the cell. For example, RIG-I-like receptors (RLRs) have evolved to detect viral RNA species and to activate the production of host defense molecules and cytokines that stimulate adaptive immune responses. In addition, host defense countermeasures, including the production of type I interferons (IFNs), can also be triggered by microbial DNA from bacteria, viruses and perhaps parasites and are regulated by the cytosolic sensor, stimulator of interferon genes (STING). STING-dependent signaling is initiated by cyclic dinucleotides (CDNs) generated by intracellular bacteria following infection. CDNs can also be synthesized by a cellular synthase, cGAS, following interaction with invasive cytosolic self-DNA or microbial DNA species. The importance of STING signaling in host defense is evident since numerous pathogens have developed strategies to prevent STING function. Here, we review the relevance of STING-controlled innate immune signaling in host defense against pathogen invasion, including microbial endeavors to subvert this critical process.

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Restoration by recombinant interferon alpha A/D of host defense systems against tumor in immunosuppressed mice

Clinical & Experimental Metastasis ◽

10.1007/bf00053471 ◽

1986 ◽

Vol 4 (1) ◽

pp. 35-44 ◽

Cited By ~ 3

Author(s):

Junko Nishimura ◽

Kahori Mitsui ◽

Yutaka Tanaka ◽

Ryuko Yamamoto ◽

Yasuji Suhara ◽

...

Keyword(s):

Interferon Alpha ◽

Host Defense ◽

Recombinant Interferon ◽

Defense Systems ◽

Recombinant Interferon Alpha ◽

Immunosuppressed Mice

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Detection of spacer precursors formed in vivo during primed CRISPR adaptation

Nature Communications ◽

10.1038/s41467-019-12417-w ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 11

Author(s):

Anna A. Shiriaeva ◽

Ekaterina Savitskaya ◽

Kirill A. Datsenko ◽

Irina O. Vvedenskaya ◽

Iana Fedorova ◽

...

Keyword(s):

Escherichia Coli ◽

Nucleic Acid ◽

High Throughput Sequencing ◽

Dna Degradation ◽

Type I ◽

Dna Fragments ◽

Crispr Array ◽

Foreign Dna ◽

And Function

Abstract Type I CRISPR-Cas loci provide prokaryotes with a nucleic-acid-based adaptive immunity against foreign DNA. Immunity involves adaptation, the integration of ~30-bp DNA fragments, termed prespacers, into the CRISPR array as spacers, and interference, the targeted degradation of DNA containing a protospacer. Interference-driven DNA degradation can be coupled with primed adaptation, in which spacers are acquired from DNA surrounding the targeted protospacer. Here we develop a method for strand-specific, high-throughput sequencing of DNA fragments, FragSeq, and apply this method to identify DNA fragments accumulated in Escherichia coli cells undergoing robust primed adaptation by a type I-E or type I-F CRISPR-Cas system. The detected fragments have sequences matching spacers acquired during primed adaptation and function as spacer precursors when introduced exogenously into cells by transformation. The identified prespacers contain a characteristic asymmetrical structure that we propose is a key determinant of integration into the CRISPR array in an orientation that confers immunity.

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