Using an Endogenous CRISPR-Cas System for Genome Editing in the Human Pathogen Clostridium difficile.

Appl Environ Microbiol

Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvete, France

Published: October 2019

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Article Abstract

The human enteropathogen constitutes a key public health issue in industrialized countries. Many aspects of pathophysiology and adaptation inside the host remain poorly understood. We have recently reported that this bacterium possesses an active CRISPR-Cas system of subtype I-B for defense against phages and other mobile genetic elements that could contribute to its success during infection. In this paper, we demonstrate that redirecting this endogenous CRISPR-Cas system toward autoimmunity allows efficient genome editing in We provide a detailed description of this newly developed approach and show, as a proof of principle, its efficient application for deletion of a specific gene in reference strain 630Δ and in epidemic strain R20291. The new method expands the arsenal of the currently limiting set of gene engineering tools available for investigation of and may serve as the basis for new strategies to control infections. represents today a real danger for human and animal health. It is the leading cause of diarrhea associated with health care in adults in industrialized countries. The incidence of these infections continues to increase, and this trend is accentuated by the general aging of the population. Many questions about the mechanisms contributing to 's success inside the host remain unanswered. The set of genetic tools available for this pathogen is limited, and new developments are badly needed. has developed efficient defense systems that are directed against foreign DNA and that could contribute to its survival in phage-rich gut communities. We show how one such defense system, named CRISPR-Cas, can be hijacked for genome editing. Our results also show a great potential for the use of the CRISPR-Cas system for the development of new therapeutic strategies against infections.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805081PMC
http://dx.doi.org/10.1128/AEM.01416-19DOI Listing

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