Publications by authors named "Jeffrey K Cornuault"

6 Publications

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Zebrafish: a big fish in the study of the gut microbiota.

Curr Opin Biotechnol 2021 Oct 12;73:308-313. Epub 2021 Oct 12.

Département de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Québec, QC, G1V 0A6, Canada; Groupe de recherche en écologie buccale, Faculté de médecine dentaire, Université Laval, Québec, QC, G1V 0A6, Canada; Félix d'Hérelle Reference Center for Bacterial Viruses, Université Laval, Québec, QC, G1V 0A6, Canada. Electronic address:

The importance of the gut microbiota in host health is now well established, but the underlying mechanisms remain poorly understood. Among the animal models used to investigate microbiota-host interactions, the zebrafish (Danio renio) is gaining attention. Several factors contribute to the recent interest in this model, including its low cost, the ability to assess large cohorts, the possibility to obtain germ-free larvae from non-axenic parents, and the availability of optical methodologies to probe the transparent larvae and adults from various genetic lines. We review recent findings on the zebrafish gut microbiota and its modulation by exogenous microbes, nutrition, and environmental factors. We also highlight the potential of this model for assessing the impact of the gut microbiota on brain development.
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http://dx.doi.org/10.1016/j.copbio.2021.09.007DOI Listing
October 2021

Induction and Elimination of Prophages Using CRISPR Interference.

CRISPR J 2021 08;4(4):549-557

Département de Biochimie, de Mmicrobiologie, et de Bio-informatique, Faculté des sciences et de Génie, Université Laval, Québec City, Canada; Université Laval, Québec City, Canada.

Prophages are widely spread among bacterial genomes, and they can have positive or negative effects on their hosts. A key aspect in the study of prophages is the discovery of their induction signals. Prophage induction can occur by inactivating a phage transcriptional repressor, which is responsible for maintaining the lysogenic state. This repressor can be inactivated through the bacterial SOS response. However, the induction signals for numerous prophages do not involve the SOS system, and therefore significant efforts are needed to identify these conditions. Similarly, curing bacterial strains of inducible prophages is a tedious process, requiring the screening of several colonies. Here, we investigated whether transcriptional silencing of a prophage repressor using CRISPR interference (CRISPRi) would lead to prophage induction. Using phages λ and P2 as models, we demonstrated the efficiency of CRISPRi for prophage induction and for curing lysogenic strains of their prophages.
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http://dx.doi.org/10.1089/crispr.2021.0026DOI Listing
August 2021

A Jumbo Formation in the Viral Game Plan.

CRISPR J 2020 02;3(1):14-17

Département de biochimie, de microbiologie et de bio-informatique, Faculté des sciences et de génie, Université Laval, Québec, Canada; Université Laval, Québec, Canada.

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http://dx.doi.org/10.1089/crispr.2020.29082.jcoDOI Listing
February 2020

The enemy from within: a prophage of Roseburia intestinalis systematically turns lytic in the mouse gut, driving bacterial adaptation by CRISPR spacer acquisition.

ISME J 2020 03 11;14(3):771-787. Epub 2019 Dec 11.

Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350, Jouy-en-Josas, France.

Despite an overall temporal stability in time of the human gut microbiota at the phylum level, strong variations in species abundance have been observed. We are far from a clear understanding of what promotes or disrupts the stability of microbiome communities. Environmental factors, like food or antibiotic use, modify the gut microbiota composition, but their overall impacts remain relatively low. Phages, the viruses that infect bacteria, might constitute important factors explaining temporal variations in species abundance. Gut bacteria harbour numerous prophages, or dormant viruses, which can evolve to become ultravirulent phage mutants, potentially leading to important bacterial death. Whether such phenomenon occurs in the mammal's microbiota has been largely unexplored. Here we studied temperate phage-bacteria coevolution in gnotoxenic mice colonised with Roseburia intestinalis, a dominant symbiont of the human gut microbiota, and Escherichia coli, a sub-dominant member of the same microbiota. We show that R. intestinalis L1-82 harbours two active prophages, Jekyll and Shimadzu. We observed the systematic evolution in mice of ultravirulent Shimadzu phage mutants, which led to a collapse of R. intestinalis population. In a second step, phage infection drove the fast counter-evolution of host phage resistance mainly through phage-derived spacer acquisition in a clustered regularly interspaced short palindromic repeats array. Alternatively, phage resistance was conferred by a prophage originating from an ultravirulent phage with a restored ability to lysogenize. Our results demonstrate that prophages are a potential source of ultravirulent phages that can successfully infect most of the susceptible bacteria. This suggests that prophages can play important roles in the short-term temporal variations observed in the composition of the gut microbiota.
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http://dx.doi.org/10.1038/s41396-019-0566-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031369PMC
March 2020

Phages infecting Faecalibacterium prausnitzii belong to novel viral genera that help to decipher intestinal viromes.

Microbiome 2018 04 3;6(1):65. Epub 2018 Apr 3.

Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.

Background: Viral metagenomic studies have suggested a role for bacteriophages in intestinal dysbiosis associated with several human diseases. However, interpretation of viral metagenomic studies is limited by the lack of knowledge of phages infecting major human gut commensal bacteria, such as Faecalibacterium prausnitzii, a bacterial symbiont repeatedly found depleted in inflammatory bowel disease (IBD) patients. In particular, no complete genomes of phages infecting F. prausnitzii are present in viral databases.

Methods: We identified 18 prophages in 15 genomes of F. prausnitzii, used comparative genomics to define eight phage clades, and annotated the genome of the type phage of each clade. For two of the phages, we studied prophage induction in vitro and in vivo in mice. Finally, we aligned reads from already published viral metagenomic data onto the newly identified phages.

Results: We show that each phage clade represents a novel viral genus and that a surprisingly large fraction of them (10 of the 18 phages) codes for a diversity-generating retroelement, which could contribute to their adaptation to the digestive tract environment. We obtained either experimental or in silico evidence of activity for at least one member of each genus. In addition, four of these phages are either significantly more prevalent or more abundant in stools of IBD patients than in those of healthy controls.

Conclusion: Since IBD patients generally have less F. prausnitzii in their microbiota than healthy controls, the higher prevalence or abundance of some of its phages may indicate that they are activated during disease. This in turn suggests that phages could trigger or aggravate F. prausnitzii depletion in patients. Our results show that prophage detection in sequenced strains of the microbiota can usefully complement viral metagenomic studies.
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http://dx.doi.org/10.1186/s40168-018-0452-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883640PMC
April 2018

Inflammation boosts bacteriophage transfer between spp.

Science 2017 03 16;355(6330):1211-1215. Epub 2017 Mar 16.

Institute of Microbiology, ETH Zurich, Switzerland.

Bacteriophage transfer (lysogenic conversion) promotes bacterial virulence evolution. There is limited understanding of the factors that determine lysogenic conversion dynamics within infected hosts. A murine Typhimurium (Tm) diarrhea model was used to study the transfer of SopEΦ, a prophage from Tm SL1344, to Tm ATCC14028S. Gut inflammation and enteric disease triggered >55% lysogenic conversion of ATCC14028S within 3 days. Without inflammation, SopEΦ transfer was reduced by up to 10-fold. This was because inflammation (e.g., reactive oxygen species, reactive nitrogen species, hypochlorite) triggers the bacterial SOS response, boosts expression of the phage antirepressor Tum, and thereby promotes free phage production and subsequent transfer. Mucosal vaccination prevented a dense intestinal Tm population from inducing inflammation and consequently abolished SopEΦ transfer. Vaccination may be a general strategy for blocking pathogen evolution that requires disease-driven transfer of temperate bacteriophages.
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http://dx.doi.org/10.1126/science.aaf8451DOI Listing
March 2017
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