Chitin Synthases with a Myosin Motor-Like Domain Control the Resistance of Aspergillus fumigatus to Echinocandins
Chitin Synthases with a Myosin Motor-Like Domain Control the Resistance of Aspergillus fumigatus to Echinocandins
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DOI：
10.1128/aac.00752-12
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发表时间：
2012-12-01
影响因子：
4.9
通讯作者：
Latge, Jean-Paul
中科院分区：
文献类型：
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作者：
Jimenez-Ortigosa, Cristina;Aimanianda, Vishukumar;Latge, Jean-Paul
烟曲霉具有两种几丁质酶（CSMA和CSMB），其具有以头对头构型排列的肌球蛋白马达样结构域（MMD）。为了了解这些几丁质酶的功能，构建了单和双csm突变株并进行了分析。虽然有一个轻微的减少，在菌丝生长的突变体，总几丁质合成酶的活性和细胞壁几丁质含量是相似的所有的突变体和亲本菌株的菌丝体。在分生孢子中，Delta csmA菌株细胞壁中的几丁质含量小于亲本菌株中发现的量的一半。相比之下，Delta csmB突变菌株和出乎意料的Delta csmA/Delta csmB突变菌株在它们的分生孢子细胞壁中没有显示出几丁质含量的任何改变。与亲本菌株的疏水性分生孢子相反，所有csm突变体的分生孢子都是亲水性的，这是由于存在覆盖疏水性表面小棒层的无定形材料。CSM基因的缺失也导致了休眠和萌发的分生孢子对棘白菌素的敏感性增加。这些结果表明，缺失的CSMA和CSMB基因诱导细胞壁结构的显着解体，即使他们只微弱的贡献，整个细胞壁几丁质合成。
Aspergillus fumigatus has two chitin synthases (CSMA and CSMB) with a myosin motor-like domain (MMD) arranged in a head-to-head configuration. To understand the function of these chitin synthases, single and double csm mutant strains were constructed and analyzed. Although there was a slight reduction in mycelial growth of the mutants, the total chitin synthase activity and the cell wall chitin content were similar in the mycelium of all of the mutants and the parental strain. In the conidia, chitin content in the Delta csmA strain cell wall was less than half the amount found in the parental strain. In contrast, the Delta csmB mutant strain and, unexpectedly, the Delta csmA/Delta csmB mutant strain did not show any modification of chitin content in their conidial cell walls. In contrast to the hydrophobic conidia of the parental strain, conidia of all of the csm mutants were hydrophilic due to the presence of an amorphous material covering the hydrophobic surface-rodlet layer. The deletion of CSM genes also resulted in an increased susceptibility of resting and germinating conidia to echinocandins. These results show that the deletion of the CSMA and CSMB genes induced a significant disorganization of the cell wall structure, even though they contribute only weakly to the overall cell wall chitin synthesis.