{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:28:34Z","timestamp":1787016514539,"version":"build-2736575974"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T00:00:00Z","timestamp":1511308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI109025"],"award-info":[{"award-number":["AI109025"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000997","name":"Arnold and Mabel Beckman Foundation","doi-asserted-by":"publisher","award":["Arnold O. Beckman postdoctoral fellowship"],"award-info":[{"award-number":["Arnold O. Beckman postdoctoral fellowship"]}],"id":[{"id":"10.13039\/100000997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:named-content content-type=\"genus-species\">Candida<\/jats:named-content>\n                    species are a part of the human microbiome and can cause systemic infection upon immune suppression.\n                    <jats:named-content content-type=\"genus-species\">Candida glabrata<\/jats:named-content>\n                    infections are increasing and have greater rates of antifungal resistance than other species. Here, we present a\n                    <jats:named-content content-type=\"genus-species\">C. glabrata<\/jats:named-content>\n                    gastrointestinal (GI) colonization model to explore whether colonized yeast exposed to caspofungin, an echinocandin antifungal, develop characteristic resistance mutations and, upon immunosuppression, breakthrough causing systemic infection. Daily therapeutic dosing (5 mg\/kg of body weight) of caspofungin resulted in no reduction in fecal burdens, organ breakthrough rates similar to control groups, and resistance rates (0 to 10%) similar to those reported clinically. Treatment with 20 mg\/kg caspofungin initially reduced burdens, but a rebound following 5 to 9 days of treatment was accompanied by high levels of resistance (\n                    <jats:italic>FKS1<\/jats:italic>\n                    \/\n                    <jats:italic>FKS2<\/jats:italic>\n                    mutants). Although breakthrough rates decreased in this group, the same\n                    <jats:italic>FKS<\/jats:italic>\n                    mutants were recovered from organs. In an attempt to negate drug tolerance that is critical for resistance development, we cotreated mice with daily caspofungin and the chitin synthase inhibitor nikkomycin Z. The largest reduction (3 log) in GI burdens was obtained within 3 to 5 days of 20 mg\/kg caspofungin plus nikkomycin treatment. Yet, echinocandin resistance, characterized by a novel Fks1-L630R substitution, was identified following 5 to 7 days of treatment. Therapeutic caspofungin plus nikkomycin treatment left GI burdens unchanged but significantly reduced organ breakthrough rates (20%;\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). Single-dose pharmacokinetics demonstrated low levels of drug penetration into the GI lumen posttreatment with caspofungin. Overall, we show that\n                    <jats:named-content content-type=\"genus-species\">C. glabrata<\/jats:named-content>\n                    echinocandin resistance can arise within the GI tract and that resistant mutants can readily disseminate upon immunosuppression.\n                  <\/jats:p>","DOI":"10.1128\/aac.01412-17","type":"journal-article","created":{"date-parts":[[2017,10,2]],"date-time":"2017-10-02T20:30:26Z","timestamp":1506976226000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["The Gastrointestinal Tract Is a Major Source of Echinocandin Drug Resistance in a Murine Model of Candida glabrata Colonization and Systemic Dissemination"],"prefix":"10.1128","volume":"61","author":[{"given":"Kelley R.","family":"Healey","sequence":"first","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoji","family":"Nagasaki","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Kordalewska","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Park","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Perlin","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00029-06"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02474-10"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2012.10.003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23466"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit136"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.06112-11"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2011.140685"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ1194"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12831"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017589"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00074-13"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00065-15"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01995"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2008.11.006"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809793106"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01542-07"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01486-12"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00655-16"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11128"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhin.2009.02.009"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153247"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.32.4.975-980.1994"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1086\/422002"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01584-09"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00621-11"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1086\/598933"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1177\/0897190013515927"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.12.28"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.8.1.192-195.2001"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.47049-0"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn216"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2010.00611.x"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myv028"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2016.00186"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku518"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2016.07.025"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00046-13"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.1.438-440.2005"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.11.4555-4560.2005"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00836-10"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01574-16"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00443-09"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.8.3264-3273.2005"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01412-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01412-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T15:49:03Z","timestamp":1645458543000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01412-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1128\/AAC.01412-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.01412-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12]]},"assertion":[{"value":"2017-07-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-09-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01412-17"}}