2026-06-30T03:03:25Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/128182024-09-27T20:50:38Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Rao, Chitong
author
Guyard, Cyril
author
Pelaz, Carmen
author
Wasserscheid, Jessica
author
Bondy-Denomy, Joseph
author
Dewar, Ken
author
Ensminger, Alexander W
funder
University of Toronto (Cánada)
funder
Canadian Institutes of Health Research
funder
Natural Sciences and Engineering Research Council (Canada)
funder
Canada Foundation for Innovation
funder
Ontario Research Fund - Research Excellence (ORF-RE)
2021-04-29T10:32:56Z
2021-04-29T10:32:56Z
2016
Cell Microbiol . 2016 Oct;18(10):1319-38.
10.1111/cmi.12586
1462-5822
Cellular microbiology
26936325
http://hdl.handle.net/20.500.12105/12818
Clustered regularly interspaced short palindromic repeats with CRISPR-associated gene (CRISPR-Cas) systems are widely recognized as critical genome defense systems that protect microbes from external threats such as bacteriophage infection. Several isolates of the intracellular pathogen Legionella pneumophila possess multiple CRISPR-Cas systems (type I-C, type I-F and type II-B), yet the targets of these systems remain unknown. With the recent observation that at least one of these systems (II-B) plays a non-canonical role in supporting intracellular replication, the possibility remained that these systems are vestigial genome defense systems co-opted for other purposes. Our data indicate that this is not the case. Using an established plasmid transformation assay, we demonstrate that type I-C, I-F and II-B CRISPR-Cas provide protection against spacer targets. We observe efficient laboratory acquisition of new spacers under 'priming' conditions, in which initially incomplete target elimination leads to the generation of new spacers and ultimate loss of the invasive DNA. Critically, we identify the first known target of L. pneumophila CRISPR-Cas: a 30 kb episome of unknown function whose interbacterial transfer is guarded against by CRISPR-Cas. We provide evidence that the element can subvert CRISPR-Cas by mutating its targeted sequences - but that primed spacer acquisition may limit this mechanism of escape. Rather than generally impinging on bacterial fitness, this element drives a host specialization event - with improved fitness in Acanthamoeba but a reduced ability to replicate in other hosts and conditions. These observations add to a growing body of evidence that host range restriction can serve as an existential threat to L. pneumophila in the wild.
eng
Active and adaptive Legionella CRISPR-Cas reveals a recurrent challenge to the pathogen.
journal article
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URL
https://repisalud.isciii.es/bitstreams/fe2930b5-af38-4407-ac2b-00062071a18f/download
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ActiveAndAdaptiveLegionella_2016.pdf
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https://repisalud.isciii.es/bitstreams/43d490a2-bb0d-494c-b0ea-b5d8950e60eb/download
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text/plain
ActiveAndAdaptiveLegionella_2016.pdf.txt