Paradoxical antifungal activity and structural observations in biofilms formed by echinocandin-resistant Candida albicans clinical isolates.
Paradoxical antifungal activity and structural observations in biofilms formed by echinocandin-resistant Candida albicans clinical isolates.
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抗棘白菌素白色念珠菌临床分离株形成的生物膜中矛盾的抗真菌活性和结构观察。
DOI：
10.1093/mmy/myt007
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发表时间：
2014
期刊：
影响因子：
2.9
通讯作者：
Lee,SamuelA
中科院分区：
文献类型：
--
作者：
Walraven,CarlaJ;Bernardo,StellaM;Wiederhold,NathanP;Lee,SamuelA
棘白菌素耐药的白色念珠菌临床分离株已有报道，在这些（卡泊芬净耐药[CAS-R]）菌株中已鉴定出编码主要葡聚糖合酶亚基的FKS 1基因的关键热点突变。虽然这些突变导致棘白菌素的表型耐药的细胞，有很少的数据，抗真菌药CAS-RC。生物膜内的白色菌株。因此，我们分析了由12 C形成的生物膜。白念珠菌CAS-R临床菌株中，我们以前确定了FKS 1热点突变，并比较了阿尼芬净（ANID），卡泊芬净（CAS）和米卡芬净（云母）的无柄抗真菌和矛盾活性。在96孔静态微孔板模型中形成生物膜，并使用四唑盐还原和结晶紫测定法以及扫描电子显微镜检查进行测定。我们首先试图评估这些fks 1突变体的生物膜形成和结构，发现与参考菌株SC 5314相比，大多数fks 1突变体的生物膜质量和代谢活性降低。结构分析显示，fks 1突变体生物膜一般密度较低，酵母菌和假菌丝明显占优势，具有不寻常的“坑”样细胞表面结构。我们还注意到，除一种菌株外，所有菌株对ANID、CAS和云母的固着最低抑菌浓度（MIC）均高于非固着MIC。大多数菌株表现出一种矛盾的效果（PE），以特定的棘白菌素，无论是刺突或无柄的形式。总体而言，棘白菌素耐药临床分离株形成的生物膜表现出不同的棘白菌素PE，其结构特征是酵母菌，假菌丝和坑状结构的优势。
Echinocandin-resistant clinical isolates ofCandida albicanshave been reported, and key-hot spot mutations in theFKS1gene, which encodes a major glucan synthase subunit, have been identified in these (caspofungin-resistant [CAS-R]) strains. Although these mutations result in phenotypic resistance to echinocandins in planktonic cells, there is little data on antifungal susceptibilities of CAS-RC. albicansstrains within biofilms. Thus, we analyzed biofilms formed by 12C. albicansCAS-R clinical strains in which we previously identifiedFKS1hot-spot mutations and compared the sessile antifungal and paradoxical activity of anidulafungin (ANID), caspofungin (CAS), and micafungin (MICA). Biofilms were formed in a 96-well static microplate model and assayed using both tetrazolium-salt reduction and crystal violet assays, as well as examination by scanning electron microscopy. We first sought to assess biofilm formation and structure in thesefks1mutants and found that the biofilm mass and metabolic activities were reduced in most of thefks1mutants as compared with reference strain SC5314. Structural analyses revealed that thefks1mutant biofilms were generally less dense and had a clear predominance of yeast and pseudohyphae, with unusual “pit”-like cell surface structures. We also noted that sessile minimum inhibitory concentrations (MICs) to ANID, CAS, and MICA were higher than planktonic MICs of all but one strain. The majority of strains demonstrated a paradoxical effect (PE) to particular echinocandins, in either planktonic or sessile forms. Overall, biofilms formed by echinocandin-resistant clinical isolates demonstrated varied PEs to echinocandins and were structurally characterized by a preponderance of yeast, pseudohyphae, and pit-like structures.