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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Changes in cell wall synthesis and ultrastructure during paradoxical growth effect of caspofungin on four different Candida species.
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Changes in cell wall synthesis and ultrastructure during paradoxical growth effect of caspofungin on four different Candida species.

机译：卡泊芬净对四种不同念珠菌的反常生长作用期间细胞壁合成和超微结构的变化。

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摘要

Paradoxical growth (PG) has been described for echinocandins and is characterized by cell growth at drug concentrations above the MIC. In this study, two isolates each of Candida albicans, C. tropicalis, C. orthopsilosis, and C. parapsilosis, all of which displaying PG in response to caspofungin, were subjected to MIC, minimal fungicidal concentration (MFC), and time-kill curve assays to evaluate the levels of PG. Cell wall components and ultrastructural modifications of the PG cells were also investigated. The results showed that when cell growth and survival were evaluated by MFC or time-kill curve assays, high concentrations of caspofungin did not show fungicidal activity against PG cells. Furthermore, for C. parapsilosis and C. orthopsilosis, time-kill curves were more discriminatory than MFCs in detecting the PG effect. The four different Candida species studied demonstrated similar alterations in cell wall components and ultrastructure associated with PG. In PG cells, beta-1,3-glucan content decreased from 2.7- to 7.8-fold, whereas chitin content increased from 4.0- to 6.6-fold. An electron microscopy study of the PG cells revealed morphological alterations, clumping of cells, enlarged cells, the absence of filamentation, abnormal septa, and accumulation of chitin in the cell wall. Also, PG cells basically exhibited a single dark high-density layer in the cell wall, indicating the loss of the beta-1,3-glucan layer. Our results present novel details about the ultrastructural alterations that occur in C. albicans, C. parapsilosis, C. orthopsilosis, and C. tropicalis during PG and show that chitin is the major component of the cell walls of PG cells. Stimulation of chitin synthesis may represent a rescue mechanism against caspofungin activity.
机译：已经描述了棘球ins素的反常生长（PG），其特征在于药物浓度高于MIC时细胞生长。在这项研究中，分别对白色念珠菌，热带念珠菌，正念念珠菌和副念珠菌的两个分离株进行了MIC，最小杀菌浓度（MFC）和杀灭作用，它们均对卡泊芬净具有响应性曲线分析以评估PG的水平。还研究了PG细胞的细胞壁成分和超微结构修饰。结果表明，当通过MFC或时间杀灭曲线测定法评估细胞的生长和存活时，高浓度的卡泊芬净对PG细胞没有杀真菌活性。此外，对于C. parapsilosis和C. orthopsilosis，在检测PG效应方面，时间杀灭曲线比MFC具有更多的判别力。研究的四种不同的念珠菌物种显示了与PG相关的细胞壁成分和超微结构的相似变化。在PG细胞中，β-1,3-葡聚糖含量从2.7倍降至7.8倍，而几丁质含量从4.0倍增至6.6倍。对PG细胞进行的电子显微镜研究显示，其形态发生了改变，细胞团块，细胞增大，丝不存在，隔垫不正常以及几丁质在细胞壁中积累。同样，PG细胞在细胞壁上基本上表现出单个深色的高密度层，表明β-1，3-葡聚糖层的损失。我们的研究结果提供了有关在PG期间在白色念珠菌，C。parapsilosis，C。orthopsilosis和C.tropicis中发生的超微结构改变的新颖详细信息，并显示几丁质是PG细胞细胞壁的主要成分。几丁质合成的刺激可能代表一种抗卡泊芬净活性的拯救机制。

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