作者：雷雨欣, 宋自力, 王东, 尹文兵
单位：1 沈阳药科大学中药学院，辽宁 沈阳 110016,2 中国科学院微生物研究所微生物多样性和资源创新利用国家重点实验室，北京 100101,3 中国科学院大学医学院，北京 100049
关键词：烟曲霉,calmidazolium chloride,抗真菌活性,广谱作用,联合用药
基金：国家自然科学基金(32470046),中国科学院基础研究青年团队项目(YSBR-111)
烟曲霉是引起侵袭性曲霉病的关键病原体，严重威胁着人类生命健康。钙调蛋白通路在调控烟曲霉毒力方面起着关键作用，成为抗真菌研究的重要靶点。本研究针对FDA批准的活性化合物库进行系统筛选，成功发现calmidazolium chloride (CMZ)对烟曲霉生长具有显著抑制效果。通过测定不同浓度CMZ对烟曲霉生长、分生孢子存活和萌发、次级代谢以及钙离子信号通路基因表达的影响，全面解析了其抗烟曲霉的作用机制。研究结果表明：CMZ表现出强效的杀菌活性，对烟曲霉的致死率高达(98.96±1.47)%，同时能够抑制(85.26±1.51)%的分生孢子萌发，并导致毒力相关次级代谢产物helvolic acid丰度降低了98.02%。在机制上，本研究揭示了CMZ是烟曲霉钙调蛋白激酶转录抑制剂，通过干扰细胞内钙离子浓度来发挥抗真菌作用。此外，CMZ在与两性霉素B联合使用时，能够发挥明显的协同作用，增强两性霉素B的杀菌作用。进一步研究发现，CMZ对不同来源的病原真菌，包括冻土毛霉、黄曲霉和尖孢镰孢菌均有不同程度的抑制作用，抑制率分别为(24.65±0.90)%、(51.99±0.54)%和(49.98±1.62)%，充分显示出广谱的抗真菌活性。因此，本研究全面评价了钙调蛋白激酶转录抑制剂CMZ的广谱抗真菌活性以及与两性霉素B的协同抗真菌作用，为真菌感染防控提供了极具潜力的候选化合物及联合用药方案。"/>template{display:none;}.mag-rich-xref-fn { cursor: pointer;}//长视频$(document).ready(function(){if($("#showLongArticleVideo") && $("#showLongArticleVideo").length && $("#showLongArticleVideo").length>0){mag_ajax_update({ele_id:'showLongArticleVideo',url:mag_currentQikanUrl() + "/CN/article/showLongArticleVideo.do?id="+$("#articleId").val()});}});//可视化图谱$(document).ready(function(){if($("#showArticle_knowledgeMap") && $("#showArticle_knowledgeMap").length && $("#showArticle_knowledgeMap").length>0){jQuery.getJSON("/Jwxb/CN/lexeme/existsCnctstInArticle.do?articleID="+$("#articleId").val(), null, function(json){if(json.result){$("#showArticle_knowledgeMap").show();}});}});$(document).ready(function(){var metaDataStr = $.trim($("#article_metaJson").val());if(metaDataStr!=''){eval("window.metaData="+metaDataStr);}if(window.metaData && (!window.metaData.authorNotesCommon_cn && !window.metaData.authorNotesCorresp_cn && window.metaData.authorNotes_cn)){window.metaData.authorNotesCommon_cn = window.metaData.authorNotes_cn;}if(window.metaData && (!window.metaData.authorNotesCommon_en && !window.metaData.authorNotesCorresp_en && window.metaData.authorNotes_en)){window.metaData.authorNotesCommon_en = window.metaData.authorNotes_en;}var _nlmdtdXml = $("#article_nlmdtdXml").val();var magDir = _nlmdtdXml.replace(/\/[^\/]+$/,'');window.metaData.magDir = magDir;new mag_vue({ el: '#metaVue', //dataUrl: mag_currentQikanUrl() + '/EN/article/getRichHtmlJson.do?articleId='+$("#articleId").val(), data:window.metaData, loading:true, doTextFun:function(text){ return doDataJsonText(text); 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来源：2025年第8期
《菌物学报》期刊编辑部
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