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白念珠菌是人体重要的条件性致病真菌。形态的多样性和可塑性是白念珠菌典型的生物学特征,这与它的致病性、宿主适应能力以及有性生殖过程密切相关。白念珠菌生物被膜(Biofilm)是由不同形态细胞(包括酵母型、菌丝和假菌丝)以及胞外基质组成的致密结构,也是毒性和耐药性形成的重要因子。生物被膜对抗真菌药物、宿主免疫系统和环境胁迫因子等都表现出较强的抵抗力和耐受性,是临床上病原真菌感染防治的重大挑战。随着基因表达谱和遗传操作技术的发展,白念珠菌生物被膜的形成及其耐药性的获得所依赖的遗传调控通路和分子调控机制越来越清楚。主要包括MAPK和cAMP介导的信号途径以及Bcr1和Tec1等因子介导的转录调控。此外,白念珠菌生物被膜的形成与形态转换和有性生殖之间存在密切的联系。文中综述了白念珠菌生物被膜形成的遗传调控机制,重点介绍了细胞壁相关蛋白、转录因子和交配型对该过程的调控以及生物被膜的耐药机制。 相似文献
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难治性真菌感染的临床分析发现,病灶感染病原常以生物被膜的形态存在。生物被膜的形成可帮助真菌躲避宿主细胞免疫系统清除和药物的攻击,所造成的持续性感染严重威胁人类健康,因此,认识研究真菌生物被膜及其耐药机理对于防治临床真菌感染有着重大意义。白色念珠菌是一种临床感染常见的条件性致病菌,也是目前真菌生物被膜研究的主要研究模型。白色念珠菌生物被膜主要由多糖、蛋白质和DNA构成,其形成由微生物间的群体感应调控,并受到环境中营养成分及其附着物表面性质影响。研究发现,胞外基质的屏障作用、耐药基因的表达等机制与生物被膜耐药性的产生密切相关。本文就白色念珠菌生物被膜的形成过程、结构组成、形成的影响因素、现有研究模型、耐药机制和治疗策略等几个方面介绍近年来的研究进展。 相似文献
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目的:研究黄芩素与氟康唑合用对白念珠菌生物被膜形成的影响。方法采用激光共聚焦显微镜观察黄芩素与氟康唑合用对白念珠菌生物被膜生长形态的影响;采用 XTT 法考察黄芩素与氟康唑合用对白念珠菌生物被膜形成能力的影响;应用水-烃两相测定实验考察黄芩素与氟康唑合用对白念珠菌生物被膜细胞表面疏水性( Cell surface hydrophobicity, CSH)的影响;应用实时定量 RT-PCR(Real Time RT-PCR)实验考察黄芩素与氟康唑合用对白念珠菌 CSH1、EFG1、HWP1、ALS1基因表达的影响。结果黄芩素与氟康唑合用能够协同抑制白念珠菌生物被膜的形成,经黄芩素与氟康唑处理的白念珠菌不能形成正常的生物被膜,其生长动力学及细胞表面疏水性下降,细胞疏水性相关基 CSH1、菌丝形成调控基因EFG1、黏附相关基因 HWP1基因的表达水平降低。结论黄芩素与氟康唑合用可协同抑制白念珠菌生物被膜的形成。 相似文献
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生物被膜的形成是白色念珠菌产生耐药性的重要原因之一。本研究首先构建白色念珠菌体外生物被膜模型,通过倒置显微镜和甲基四氮盐(XTT)法检测大蒜素对白色念珠菌生物被膜形成的影响,同时采用实时荧光定量PCR法(qRT-PCR)对白色念珠菌生物被膜相关基因ALS1、ALS3、HWP1、MP65、SUN41的表达水平进行检测。结果显示,当大蒜素浓度≥12.5μg/mL时,白色念珠菌生物被膜的生长被抑制,并且在生物被膜形成的早期,大蒜素干预能有效抑制其形成;大蒜素能下调白色念珠菌生物被膜相关基因ALS1、ALS3、HWP1、MP65、SUN41的表达水平。研究结果提示,大蒜素可有效抑制体外白色念珠菌生物被膜的形成,可能与其下调生物被膜相关基因的表达有关。 相似文献
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<正>白念珠菌(Candida albicans)作为条件致病菌与人体共存,一般情况下不会引发感染,当机体免疫力低下或其他条件因素影响,可能引发黏膜或全身感染[1]。白念珠菌导致的口腔念珠菌病、念珠菌性阴道炎等多种疾病呈逐年上升的趋势[2]。还可与其他致病菌产生相互促进作用,如在口腔中与卟啉单胞菌形成混合生物膜,使牙周围组织遭到明显的破坏[3]。目前抑制白念珠菌的药物库资源有限,临床使用的治疗药物虽然能够有效治疗白念珠菌的侵袭性感染,但其毒副作用可能对人体造成不可逆的伤害同时菌株对药物的敏感性也逐渐降低产生耐药性。为解决这一系列问题,亟需开发新型有效抗菌物质,而生物源中的天然活性物质具有来源广泛、种类繁多等特点可以为此提供基础[4]。学者们对白念珠菌致病机理和药物作用靶点进行了深入研究,并从植物源、动物源和微生物源积极寻找抑制白念珠菌的相关天然活性物质,为解决化学药物带来的不良反应提供了基础。本文对白念珠菌的形态特征、致病机理以及不同生物源对白念珠菌的抑制作用等方面的研究进行综述和分析,... 相似文献
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目的 研究CRK1基因缺失对白念珠菌形态、黏附、生物被膜的影响.方法 显微镜下观察,计算菌丝形成率,比较CRK1基因缺失菌(Δcrk1菌)及标准菌SC5314形成菌丝的能力;建立肠黏膜模型,计算黏附率,评价CRK1基因缺失对白念珠菌黏附的影响;MTT法及结晶紫法(CV)评价CRK1基因缺失对白念珠菌生物被膜形成的影响.结果 与SC5314相比,Δcrk1菌分别在10%胎牛血清和RPMI-1640培养条件下形成菌丝能力均较弱,两者之间有统计学差异;Δcrk1菌在60、90、120 min时对肠黏膜的黏附数明显少于标准菌SC5314,两者之间有统计学差异;通过MTT法、结晶紫法两种方法证实了,在经48 h培养后,Δcrk1菌与其标准菌SC5314相比,形成生物膜的能力弱,两者之间差异有统计学差异.结论 CRK 1基因缺失影响白念珠菌菌丝二态性的转化,进而影响黏附力和生物被膜的形成. 相似文献
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D. R. Monteiro L. F. Gorup S. Silva M. Negri E. R. de Camargo R. Oliveira 《Biofouling》2013,29(7):711-719
The aim of this study was to evaluate the effect of silver nanoparticles (SN) against Candida albicans and Candida glabrata adhered cells and biofilms. SN (average diameter 5 nm) were synthesized by silver nitrate reduction with sodium citrate and stabilized with ammonia. Minimal inhibitory concentration (MIC) tests were performed for C. albicans (n = 2) and C. glabrata (n = 2) grown in suspension following the Clinical Laboratory Standards Institute microbroth dilution method. SN were applied to adhered cells (2 h) or biofilms (48 h) and after 24 h of contact their effect was assessed by enumeration of colony forming units (CFUs) and quantification of total biomass (by crystal violet staining). The MIC results showed that SN were fungicidal against all strains tested at very low concentrations (0.4–3.3 μg ml?1). Furthermore, SN were more effective in reducing biofilm biomass when applied to adhered cells (2 h) than to pre-formed biofilms (48 h), with the exception of C. glabrata ATCC, which in both cases showed a reduction ~90%. Regarding cell viability, SN were highly effective on adhered C. glabrata and respective biofilms. On C. albicans the effect was not so evident but there was also a reduction in the number of viable biofilm cells. In summary, SN may have the potential to be an effective alternative to conventional antifungal agents for future therapies in Candida-associated denture stomatitis. 相似文献
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Monteiro DR Silva S Negri M Gorup LF de Camargo ER Oliveira R Barbosa DB Henriques M 《Letters in applied microbiology》2012,54(5):383-391
Aim: The purpose of this work was to evaluate the size‐dependent antifungal activity of different silver nanoparticles (SN) colloidal suspensions against Candida albicans and Candida glabrata mature biofilms. Methods and Results: The research presented herein used SN of three different average sizes (5, 10 and 60 nm), which were synthesized by the reduction of silver nitrate through sodium citrate and which were stabilized with ammonia or polyvinylpyrrolidone. Minimal inhibitory concentration (MIC) assays were performed using the microdilution methodology. The antibiofilm activity of SN was determined by total biomass quantification (by crystal violet staining) and colony forming units enumeration. MIC results showed that all SN colloidal suspensions were fungicidal against the tested strains at very low concentrations (0·4–3·3 μg ml?1). With regard to biomass quantification, SN colloidal suspensions were very effective only against C. glabrata biofilms, achieving biomass reductions around 90% at a silver concentration of 108 μg ml?1. In general, all SN suspensions promoted significant log10 reduction of the mean number of cultivable biofilm cells after exposure to silver concentrations at or higher than 108 μg ml?1. Moreover, the results showed that the particle size and the type of stabilizing agent used did not interfere in the antifungal activity of SN against Candida biofilms. Conclusions: This study suggests that SN have antifungal therapeutic potential, but further studies are still required namely regarding formulation and delivery means. Significance and Impact of the Study: SN may contribute to the development of new strategies for the improvement of oral health and quality of life particularly of the complete denture wearers. 相似文献
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穿心莲内酯体外抗白念珠菌生物膜作用的初步研究 总被引:5,自引:1,他引:5
目的研究穿心莲内酯对体外白念珠菌生物膜的影响。方法采用XTT减低法评价穿心莲内酯对白念珠菌生物膜及其黏附性的影响;镜下观察该药对白念珠菌生物膜的形态学影响;细胞毒性试验检测该药的毒副作用。结果穿心莲内酯对白念珠菌生物膜的SMIC50、SMIC80分别是250、1000μg/ml;1000μg/ml及100μg/ml时对白念珠菌的早期黏附及菌丝生长有抑制作用;对人细胞毒性较弱。结论穿心莲内酯对体外白念珠菌生物膜有显著的抑制作用。 相似文献
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大黄酚体外抗白念珠菌生物膜作用的研究 总被引:2,自引:0,他引:2
目的研究大黄酚对体外白念珠菌生物膜的影响。方法采用XTT减低法评价大黄酚对白念珠菌的生物膜及黏附性的影响;镜下观察该药对白念珠菌生物膜的形态学影响;细胞毒试验检测该药的毒副作用。结果大黄酚对白念珠菌生物膜的SMIC50、SMIC80分别为125、1000μg/ml;100μg/ml及1000μg/ml含量浓度的大黄酚对自念珠菌的早期黏附及菌丝生长有抑制作用;大黄酚对人细胞毒性较弱。结论大黄酚对体外白念珠菌生物膜有较强的抑制作用。 相似文献
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大蒜素体外抗白念珠菌生物膜作用的初步研究 总被引:2,自引:0,他引:2
目的研究大蒜素对体外白念珠菌生物膜的影响。方法 MTT法评价大蒜素对白念珠菌生物膜形成及细胞黏附的影响;血清芽管计数法评价大蒜素对白念珠菌芽管形成的影响。结果低浓度(4μg/mL)和高浓度(64μg/mL)大蒜素对白念珠菌生物膜形成的抑制率分别为(23.0±1.1)%和(95.6±0.3)%;32μg/mL大蒜素对早期(0h)、中期(12h)及成熟期(48h)生物膜的抑制率分别为(88.5±0.5)%、(63.3±0.8)%和(52.3±1.1)%;与空白对照组相比,不同浓度大蒜素(4~32μg/mL)对培养30min、60min、90min、120min的白念珠菌细胞黏附均有显著抑制作用(P0.05);空白对照组芽管形成率为(91.2±1.6)%,64μg/mL大蒜素组为(2.2±1.2)%。结论大蒜素对体外白念珠菌生物膜有较明显的抑制作用。 相似文献
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The ability of Candida albicans to adhere to subendothelial extracellular matrix (ECM) may be important in the pathogenesis of disseminated candidiasis. ECM proteins, such as fibronectin, laminin, and types I and IV collagen bind C. albicans avidly. These proteins all possess heparin-binding domains. The influence of the glycosaminoglycans (GAGS) including heparin, heparan sulfate and dextran sulfate on C. albicans adherence to subendothelial ECM and ECM proteins was studied. It was demonstrated that the GAGS inhibited C. albicans adherence to ECM and ECM proteins. This possibly occurred by the GAGS binding to the ECM proteins and, in so doing, masking a preferred ligand for C. albicans adherence. 相似文献
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目的 探讨土槿乙酸(pseudolaric acid B,PAB)对体外白假丝酵母菌生物膜的影响。方法 甲基四氮盐(XTT)法检测不同浓度PAB和AMB(两性霉素B)对白假丝酵母菌生物膜的抑制作用。血清芽管试验检测不同浓度PAB对芽管生成的影响。结果 PAB对白假丝酵母菌生物膜的SMIC50(抑制生物膜50%的药物浓度)为256~512 μg/mL;1024和512 μg/mL PAB对早期2 h生物膜的抑制率分别为(99.5±0.28)%和(97.1±0.38)%;512 μg/mL PAB对早期(2 h)、中期(8 h)及成熟期(24 h)生物膜的抑制率分别为(97.1±0.38)%、(90.4±0.32)%和(80.1±0.67)%;不同浓度PAB的血清芽管试验显示,64 μg/mL PAB可以完全抑制白假丝酵母菌的出芽生长,16 μg/mL PAB可以抑制83.5%的白假丝酵母菌出芽生长。结论 PAB对体外白假丝酵母菌生物膜有抑制作用,对白假丝酵母菌的出芽生长过程抑制作用显著。 相似文献