白色念珠菌血流分离株形成的生物膜表现出与耐药性和致病性相关的表型和转录异质性。

Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity.

作者信息

Sherry Leighann, Rajendran Ranjith, Lappin David F, Borghi Elisa, Perdoni Federica, Falleni Monica, Tosi Delfina, Smith Karen, Williams Craig, Jones Brian, Nile Chris J, Ramage Gordon

机构信息

Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, 378 Sauchiehall Street, Glasgow G2 3JZ, UK.

出版信息

BMC Microbiol. 2014 Jul 5;14:182. doi: 10.1186/1471-2180-14-182.

DOI:10.1186/1471-2180-14-182

PMID:24996549

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4105547/

Abstract

BACKGROUND

Candida albicans infections have become increasingly recognised as being biofilm related. Recent studies have shown that there is a relationship between biofilm formation and poor clinical outcomes in patients infected with biofilm proficient strains. Here we have investigated a panel of clinical isolates in an attempt to evaluate their phenotypic and transcriptional properties in an attempt to differentiate and define levels of biofilm formation.

RESULTS

Biofilm formation was shown to be heterogeneous; with isolates being defined as either high or low biofilm formers (LBF and HBF) based on different biomass quantification. These categories could also be differentiated using a cell surface hydrophobicity assay with 24 h biofilms. HBF isolates were more resistance to amphotericin B (AMB) treatment than LBF, but not voriconazole (VRZ). In a Galleria mellonella model of infection HBF mortality was significantly increased in comparison to LBF. Histological analysis of the HBF showed hyphal elements intertwined indicative of the biofilm phenotype. Transcriptional analysis of 23 genes implicated in biofilm formation showed no significant differential expression profiles between LBF and HBF, except for Cdr1 at 4 and 24 h. Cluster analysis showed similar patterns of expression for different functional classes of genes, though correlation analysis of the 4 h biofilms with overall biomass at 24 h showed that 7 genes were correlated with high levels of biofilm, including Als3, Eap1, Cph1, Sap5, Plb1, Cdr1 and Zap1.

CONCLUSIONS

Our findings show that biofilm formation is variable amongst C. albicans isolates, and categorising isolates depending on this can be used to predict how pathogenic the isolate will behave clinically. We have shown that looking at individual genes in less informative than looking at multiple genes when trying to categorise isolates at LBF or HBF. These findings are important when developing biofilm-specific diagnostics as these could be used to predict how best to treat patients infected with C. albicans. Further studies are required to evaluate this clinically.

摘要

背景

白色念珠菌感染越来越被认为与生物膜有关。最近的研究表明，生物膜形成与感染生物膜形成能力强的菌株的患者临床预后不良之间存在关联。在此，我们研究了一组临床分离株，试图评估它们的表型和转录特性，以区分和定义生物膜形成水平。

结果

生物膜形成表现出异质性；根据不同的生物量定量，分离株被定义为高生物膜形成者或低生物膜形成者（LBF和HBF）。使用细胞表面疏水性测定法对24小时生物膜进行检测，也可以区分这些类别。HBF分离株比LBF分离株对两性霉素B（AMB）治疗更具抗性，但对伏立康唑（VRZ）不敏感。在感染的大蜡螟模型中，与LBF相比，HBF的死亡率显著增加。对HBF的组织学分析显示，菌丝成分相互交织，表明具有生物膜表型。对23个与生物膜形成相关的基因进行转录分析，结果显示，除了4小时和24小时的Cdr1外，LBF和HBF之间没有显著的差异表达谱。聚类分析显示，不同功能类别的基因具有相似的表达模式，尽管对4小时生物膜与24小时总生物量的相关性分析表明，有7个基因与高水平生物膜相关，包括Als3、Eap1、Cphl、Sap5、Plb1、Cdr1和Zap1。

结论

我们的研究结果表明，白色念珠菌分离株之间的生物膜形成存在差异，根据这一点对分离株进行分类可用于预测该分离株在临床上的致病行为。我们已经表明，在试图将分离株分类为LBF或HBF时，观察单个基因不如观察多个基因信息量大。这些发现对于开发生物膜特异性诊断方法很重要，因为这些方法可用于预测如何最好地治疗白色念珠菌感染患者。需要进一步的研究来进行临床评估。