{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:47:24Z","timestamp":1792262844298,"version":"4.4.0"},"reference-count":41,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA245292"],"award-info":[{"award-number":["CA245292"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011769","name":"Scripps Research Institute","doi-asserted-by":"publisher","award":["Start-up funds"],"award-info":[{"award-number":["Start-up funds"]}],"id":[{"id":"10.13039\/100011769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011769","name":"Scripps Research Institute","doi-asserted-by":"publisher","award":["David C. Fairchild Endowed Fellowship"],"award-info":[{"award-number":["David C. Fairchild Endowed Fellowship"]}],"id":[{"id":"10.13039\/100011769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    <jats:italic>Enterococcus faecium<\/jats:italic>\n                    is a microbiota species in humans that can modulate host immunity (Griffin and Hang, 2022), but has also acquired antibiotic resistance and is a major cause of hospital-associated infections (Van Tyne and Gilmore, 2014). Notably, diverse strains of\n                    <jats:italic>E. faecium<\/jats:italic>\n                    produce SagA, a highly conserved peptidoglycan hydrolase that is sufficient to promote intestinal immunity (Rangan et al., 2016; Pedicord et al., 2016; Kim et al., 2019) and immune checkpoint inhibitor antitumor activity (Griffin et al., 2021). However, the functions of SagA in\n                    <jats:italic>E. faecium<\/jats:italic>\n                    were unknown. Here, we report that deletion of\n                    <jats:italic>sagA<\/jats:italic>\n                    impaired\n                    <jats:italic>E. faecium<\/jats:italic>\n                    growth and resulted in bulged and clustered enterococci due to defective peptidoglycan cleavage and cell separation. Moreover, \u0394\n                    <jats:italic>sagA<\/jats:italic>\n                    showed increased antibiotic sensitivity, yielded lower levels of active muropeptides, displayed reduced activation of the peptidoglycan pattern-recognition receptor NOD2, and failed to promote cancer immunotherapy. Importantly, the plasmid-based expression of SagA, but not its catalytically inactive mutant, restored \u0394\n                    <jats:italic>sagA<\/jats:italic>\n                    growth, production of active muropeptides, and NOD2 activation. SagA is, therefore, essential for\n                    <jats:italic>E. faecium<\/jats:italic>\n                    growth, stress resistance, and activation of host immunity.\n                  <\/jats:p>","DOI":"10.7554\/elife.95297","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T13:25:29Z","timestamp":1709558729000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.95297","source":"Crossref","is-referenced-by-count":22,"title":["Secreted antigen A peptidoglycan hydrolase is essential for Enterococcus faecium cell separation and priming of immune checkpoint inhibitor therapy"],"prefix":"10.7554","volume":"13","author":[{"given":"Steven","family":"Klupt","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02dxx6824","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology and Microbiology, Scripps Research","place":["La Jolla, United 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