{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T17:54:02Z","timestamp":1770227642279,"version":"3.49.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Staphylococcus aureus<\/jats:italic> (<jats:italic>S. aureus<\/jats:italic>) is one of the most common pathogenic bacteria responsible for causing a life-threatening peritonitis disease. NZX, as a variant of fungal defensin plectasin, displayed potent antibacterial activity against <jats:italic>S. aureus<\/jats:italic>. In this study, the antibacterial and resistance characteristics, pharmacokinetics, and pharmacodynamics of NZX against the <jats:italic>S. aureus<\/jats:italic> E48 and <jats:italic>S. aureus<\/jats:italic> E48-induced mouse peritonitis model were studied, respectively. NZX exhibited a more rapid killing activity to <jats:italic>S. aureus<\/jats:italic> (minimal inhibitory concentration, 1 \u03bcg\/ml) compared with linezolid, ampicillin and daptomycin, and serial passaging of <jats:italic>S. aureus<\/jats:italic> E48 for 30 days at 1\/2 \u00d7 MIC, NZX had a lower risk of resistance compared with ampicillin and daptomycin. Also, it displayed a high biocompatibility and tolerance to physiological salt, serum environment, and phagolysosome proteinase environment, except for acid environment in phagolysosome. The murine serum protein-binding rate of NZX was 89.25% measured by ultrafiltration method. Based on the free NZX concentration in serum after tail vein administration, the main pharmacokinetic parameters for T<jats:sub>1\/2<\/jats:sub>, C<jats:sub>max<\/jats:sub>, V<jats:sub>d<\/jats:sub>, MRT, and AUC ranged from 0.32 to 0.45 h, 2.85 to 20.55 \u03bcg\/ml, 1469.10 to 2073.90 ml\/kg, 0.32 to 0.56 h, and 1.11 to 8.89 \u03bcg.h\/ml, respectively. Additionally, the <jats:italic>in vivo<\/jats:italic> pharmacodynamics against <jats:italic>S. aureus<\/jats:italic> demonstrated that NZX administrated two times by tail vein at 20 mg\/kg could rescue all infected mice in the lethal mouse peritonitis model. And NZX treatment (20 mg\/kg) significantly reduced CFU counts in the liver, lung, and spleen, especially for intracellular bacteria in the peritoneal fluid, which were similar or superior to those of daptomycin. <jats:italic>In vivo<\/jats:italic> efficacies of NZX against total bacteria and intracellular bacteria were significantly correlated with three PK\/PD indices of \u0192AUC\/MIC, \u0192C<jats:sub>max<\/jats:sub>\/MIC, and \u0192T% &amp;gt; MIC analyzed by a sigmoid maximum-effect model. These results showed that NZX may be a potential candidate for treating peritonitis disease caused by intracellular <jats:italic>S. aureus<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fmicb.2022.865774","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T14:21:28Z","timestamp":1654093288000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacokinetics and Pharmacodynamics of Fungal Defensin NZX Against Staphylococcus aureus-Induced Mouse Peritonitis Model"],"prefix":"10.3389","volume":"13","author":[{"given":"Xueling","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruoyu","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da","family":"Teng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"103310","DOI":"10.1016\/j.jevs.2020.103310","article-title":"Plasma and peritoneal ceftriaxone concentrations after intraperitoneal administration in horses with septic peritonitis","volume":"96","author":"Alonso","year":"2021","journal-title":"J. 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