Genomics‐driven discovery of a novel self‐resistance mechanism in the echinocandin‐producing fungus        <i xmlns='http://www.wiley.com/namespaces/wiley'>Pezicula radicicolaPezicula radicicola

Yue Qun; Li Yan; Chen Li; Zhang Xiaoling; Liu Xingzhong; An Zhiqiang; Bills Gerald F

摘要

Summary > The echinocandins are antifungal lipopeptides targeting fungi via noncompetitive inhibition of the β‐1,3‐ <sc>d</sc> ‐glucan synthase FKS1 subunit. A novel echinocandin resistance mechanism involving an auxiliary copy of FKS1 in echinocandin‐producing fungus Pezicula radicicola NRRL 12192 was discovered. We sequenced the genome of NRRL 12192 and predicted two FKS1‐encoding genes ( prfks1n and prfks1a ), rather than a single FKS1 gene typical of filamentous ascomycetes. The prfks1a gene sits immediately adjacent to an echinocandin (sporiofungin) gene cluster, which was confirmed by disruption of prnrps4 and abolishment of sporiofungin production. Disruption of prfks1a dramatically increased the strain's sensitivity to exogenous echinocandins. In the absence of echinocandins, transcription levels of prfks1a relative to β ‐tubulin in the wild type and in Δ prnrps4 stains were similar. Moreover, prfks1a is consistently transcribed at low levels and is upregulated in the presence of exogenous echinocandin, but not during growth conditions promoting endogenous production of sporiofungin. Therefore, we conclude that prfks1a is primarily responsible for protecting the fungus against extracellular echinocandin toxicity. The presence of unclustered auxiliary copies of FKS1 with high similarity to prfks1a in two other echinocandin‐producing strains suggests that this previously unrecognized resistance mechanism may be common in echinocandin‐producing fungi of the family Dermataceae of the class Leotiomycetes. </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><abstract xmlns =“http://www.wiley.com/namespaces/wiley”type =“main”xml：lang =“en”> <title type =“main”>摘要</ title> > echinocandins是否通过非竞争性抑制β-1,3- <sc> D </ sc> -Glucan合酶FKS1亚基的非竞争性抑制抗真菌脂肽。发现了一种新的echinocandinin抵抗机理，涉及在Echinocandin制作的真菌中的FKS1辅助拷贝 Pezicula Radicicola </ i> NRR112192。我们测序了NRR112192的基因组，并预测了两个FKS1编码基因（ Prfks1N </ i>和 Prfks1a </ i>），而不是典型的丝状ascycetes的单个FKS1基因。 prfks1a </ i>基因立即邻近Echinocandin（Sporiofungin）基因簇，其通过破坏 prnrps4和孢子生成的废除来证实。 prfks1a的破坏显着增加了对外源性echinocandins的菌株的敏感性。在没有Echinocandins的情况下，相对于野生型和δ1中的β/ i> - β1/ i>在αsβ/ i>中的转录水平相似。此外， Prfks1a </ i>在低水平下始终转录，并且在外源性echinocandin存在下上调，但在促进孢子生成的内源性产生期间的生长条件下。因此，我们得出结论， Prfks1a </ i>主要负责保护真菌免受细胞外echinocandandin毒性的毒性。在另外两种Echinocandin的菌株中，具有高相似性的FKS1的未含有FKS1的辅助拷贝的存在表明，这种先前未被识别的抗性机制可能是阶级Leotiomycetes家族皮肤病的echinocandina-echinocandin的真菌中常见的。 </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" > 著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-22868/'>《Environmental microbiology 》</a> <b style="margin: 0 2px;">|</b><span>2018年第9期</span><b style="margin: 0 2px;">|</b> <span>共14页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yue Qun&option=202" target="_blank" rel="nofollow">Yue Qun;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Li Yan&option=202" target="_blank" rel="nofollow">Li Yan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Chen Li&option=202" target="_blank" rel="nofollow">Chen Li;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhang Xiaoling&option=202" target="_blank" rel="nofollow">Zhang Xiaoling;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Liu Xingzhong&option=202" target="_blank" rel="nofollow">Liu Xingzhong;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=An Zhiqiang&option=202" target="_blank" rel="nofollow">An Zhiqiang;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Bills Gerald F&option=202" target="_blank" rel="nofollow">Bills Gerald F;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Texas Therapeutics Institute The Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center at HoustonHouston TX USA;</p> <p>Texas Therapeutics Institute The Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center at HoustonHouston TX USA;</p> <p>Texas Therapeutics Institute The Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center at HoustonHouston TX USA;</p> <p>State Key Laboratory of MycologyInstitute of Microbiology Chinese Academy of SciencesBeijing People's Republic of China;</p> <p>State Key Laboratory of MycologyInstitute of Microbiology Chinese Academy of SciencesBeijing People's Republic of China;</p> <p>Texas Therapeutics Institute The Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center at HoustonHouston TX USA;</p> <p>Texas Therapeutics Institute The Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center at HoustonHouston TX USA;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li> <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span> <a href="https://www.zhangqiaokeyan.com/clc/183.html" title="微生物学">微生物学 ;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> </p> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 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Genomics‐driven discovery of a novel self‐resistance mechanism in the echinocandin‐producing fungus Pezicula radicicolaPezicula radicicola

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