{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:15:42Z","timestamp":1791915342891,"version":"4.3.4"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T00:00:00Z","timestamp":1583798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T00:00:00Z","timestamp":1588032000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Locus Biosciences"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2020,4,28]]},"abstract":"<jats:p>\n                    <jats:named-content content-type=\"genus-species\">Clostridioides difficile<\/jats:named-content>\n                    is a bacterial pathogen responsible for significant morbidity and mortality across the globe. Current therapies based on broad-spectrum antibiotics have some clinical success, but approximately 30% of patients have relapses, presumably due to the continued perturbation to the gut microbiota. Here, we show that phages can be engineered with type I CRISPR-Cas systems and modified to reduce lysogeny and to enable the specific and efficient targeting and killing of\n                    <jats:named-content content-type=\"genus-species\">C. difficile<\/jats:named-content>\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo.<\/jats:italic>\n                    Additional genetic engineering to disrupt phage modulation of toxin expression by lysogeny or other mechanisms would be required to advance a CRISPR-enhanced phage antimicrobial for\n                    <jats:named-content content-type=\"genus-species\">C. difficile<\/jats:named-content>\n                    toward clinical application. These findings provide evidence into how phage can be combined with CRISPR-based targeting to develop novel therapies and modulate microbiomes associated with health and disease.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00019-20","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T05:55:17Z","timestamp":1583733317000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":230,"title":["<i>In Vivo<\/i>\n                    Targeting of Clostridioides difficile Using Phage-Delivered CRISPR-Cas3 Antimicrobials"],"prefix":"10.1128","volume":"11","author":[{"given":"Kurt","family":"Selle","sequence":"first","affiliation":[{"name":"Locus Biosciences, Inc., Morrisville, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua R.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, 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