Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4.

Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4.
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由于基因组扩增ALS4,念珠菌Auris的临床分离株具有增强的粘附性和生物膜形成。

DOI:
10.1371/journal.ppat.1011239
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发表时间:
2023-03
期刊:
影响因子:
6.7
通讯作者:
--
中科院分区:
医学1区
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--
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金黄色念珠菌是一种新兴的多重耐药真菌病原菌,对人类健康构成新的全球性威胁。这种真菌的一个独特的形态特征是它的多细胞聚集表型,这被认为与细胞分裂缺陷有关。在这项研究中,我们报告了两个临床分离的金黄色葡萄球菌的一种新的聚集形式,由于相邻细胞和表面的粘附性增强,其生物被膜形成能力增加。与以前报道的聚集形态不同,这种新的聚集的多细胞形式的金黄色葡萄球菌在经过蛋白酶K或胰酶处理后可以变成单细胞。基因组分析表明,亚端粒粘附素基因ALS4的扩增是该菌株粘附力和生物被膜能力增强的原因。许多临床分离的金黄色葡萄球菌存在ALS4的不同拷贝数,这表明该亚端粒区域表现出不稳定性。全球转录图谱和实时定量聚合酶链式反应分析表明,ALS4的基因组扩增导致总转录水平的显著提高。与以前描述的非聚集型/酵母型和聚集型金黄色葡萄球菌相比,这种新的ALS4介导的聚集型金黄色葡萄球菌在生物被膜形成、表面定植和毒力方面表现出一些独特的特征。在过去的几年里,新出现的真菌病原体金黄色念珠菌在全球迅速传播。这种真菌被认为是一种“超级细菌”病原体,因为它具有多重耐药性和在临床环境中的高传播率。与念珠菌属的其他病原菌不同,许多临床分离的金黄色念珠菌可以形成一种独特的形态,即多细胞聚集表型,被认为是由细胞分裂缺陷引起的。在这项研究中,我们报告了从两个临床分离的金黄色葡萄球菌中观察到的一种新的聚集形式,该聚集形式增加了粘附力和生物被膜形成能力。基因组分析表明,亚端粒粘附素基因ALS4的扩增是该菌株粘附力和生物被膜能力增强的原因。与以前描述的非聚集型/酵母型和聚集型菌株相比,这种新的ALS4介导的聚集型金黄色葡萄球菌在生物被膜形成、表面定植和毒力方面表现出许多独特的特征。
Candida auris is an emerging multidrug-resistant fungal pathogen and a new global threat to human health. A unique morphological feature of this fungus is its multicellular aggregating phenotype, which has been thought to be associated with defects in cell division. In this study, we report a new aggregating form of two clinical C. auris isolates with increased biofilm forming capacity due to enhanced adherence of adjacent cells and surfaces. Unlike the previously reported aggregating morphology, this new aggregating multicellular form of C. auris can become unicellular after treatment with proteinase K or trypsin. Genomic analysis demonstrated that amplification of the subtelomeric adhesin gene ALS4 is the reason behind the strain’s enhanced adherence and biofilm forming capacities. Many clinical isolates of C. auris have variable copy numbers of ALS4, suggesting that this subtelomeric region exhibits instability. Global transcriptional profiling and quantitative real-time PCR assays indicated that genomic amplification of ALS4 results in a dramatic increase in overall levels of transcription. Compared to the previously characterized nonaggregative/yeast-form and aggregative-form strains of C. auris, this new Als4-mediated aggregative-form strain of C. auris displays several unique characteristics in terms of its biofilm formation, surface colonization, and virulence. The emerging fungal pathogen Candida auris has rapidly spread worldwide in the past several years. This fungus is considered to be a “superbug” pathogen due to its multidrug-resistant properties and high rates of transmission in clinical settings. Unlike other pathogenic species in the Candida genus, many clinical isolates of C. auris can form a unique morphology, namely a multicellular aggregating phenotype, that is thought to be caused by defects in cell division. In this study, we report a new aggregating form observed from two clinical isolates of C. auris with increased adhesion and biofilm forming capacity. Genomic analysis demonstrated that amplification of the subtelomeric adhesin gene ALS4 is the reason behind the strain’s enhanced adherence and biofilm forming capacities. Compared to the previously characterized nonaggregative/yeast-form and aggregative-form strains, this new Als4-mediated aggregative-form strain of C. auris displays many unique characteristics in terms of its biofilm formation, surface colonization, and virulence.
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