{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T13:31:59Z","timestamp":1770730319354,"version":"3.49.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Key R&D Program Project Drug Target Discovery and New Veterinary Drug Creation","award":["2022YFD1802100"],"award-info":[{"award-number":["2022YFD1802100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the in vitro and in vivo antimicrobial activity of pleuromutilin derivatives modified with C14 side-chain against Streptococcus suis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To determine the minimum inhibitory concentrations (MICs) of 268 pleuromutilin derivatives with C14 side-chain modifications against S. suis ATCC 43\u2005765 using the broth dilution method. Derivative B43, B49, B52, B53 and B54, which exhibited better antimicrobial activity, were selected for further investigation of their in vitro antibacterial effect, cytotoxicity, and in vivo antibacterial effect.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Determination activity of five derivatives against clinical strains (n\u200a=\u200a37), as well as growth and time-killing curves. Those experiments showed that all the five derivatives had good activity against S. suis in vitro. Resistance-inducing assays demonstrated that, except for B43, the derivatives had similar abilities to induce resistance to tiamulin. In addition, the five derivatives did not have erythrocyte haemolytic toxicity (0.25\u201316\u2005mg\/L) and cytotoxicity (1.25\u201380\u2005mg\/L). In the mouse thigh infection model, the derivative of B49 exhibited superior antibacterial efficacy. About 40\u2005mg\/kg B49 had good activity and improved the survival rate of mice by 33.3% in the S. suis mouse peritonitis model. Molecular docking study and scanning electron microscopy revealed that B49 can effectively bind to the active site of the 50S ribosome and disrupt cell membranes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A total of 68.66% of the 268 C14 side-chain modified pleuromutilin derivatives showed potent activity against S. suis. Among them, B49 showed good in vitro and in vivo antimicrobial effects against S. suis, indicating that B49 can be intensively studied as an antimicrobial candidate compound.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaf064","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T10:25:51Z","timestamp":1741861551000},"page":"1274-1286","source":"Crossref","is-referenced-by-count":2,"title":["<i>In vitro<\/i> and <i>in vivo<\/i> antibacterial activity, resistance analysis and molecular docking study of pleuromutilin derivatives against <i>Streptococcus suis<\/i>"],"prefix":"10.1093","volume":"80","author":[{"given":"Sujuan","family":"Wu","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University , Guangzhou 510642 ,","place":["P.R.China"]},{"name":"National Laboratory of Safety Evaluation 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