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1.
临床上生物被膜与感染的慢性迁延不愈密切相关,而生物被膜菌的分散又会造成感染的反复急性发作,给临床感染的有效控制带来很大困难。生物被膜菌的分散过程受到了遗传和环境等多因素的调控,主要是通过蜂式分散、块式分散和毯式分散3种形式来实现的。深入进行生物被膜基础研究对改变目前临床感染治疗的窘境有重大意义。 相似文献
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目的 探讨铜绿假单胞菌生物被膜对巨噬细胞的免疫逃逸作用以及相关机制。方法 用PMA刺激THP-1细胞获得巨噬细胞模型。用6孔板建膜法获得铜绿假单胞菌生物被膜菌。分别用铜绿假单胞菌的生物被膜菌和浮游菌感染巨噬细胞,观察巨噬细胞形态的变化,并检测巨噬细胞的细胞毒性和吞噬功能的变化。进一步用ELISA试剂盒检测感染的巨噬细胞培养上清中炎症细胞因子IL-1β的变化。结果 成功构建巨噬细胞模型和铜绿假单胞菌生物被膜菌模型。与感染了浮游菌的细胞相比,感染了生物被膜菌的巨噬细胞形态变化小,释放的LDH降低,吞噬功能减弱,IL-1β的表达量减少。结论 铜绿假单胞菌生物被膜菌可以逃逸巨噬细胞的免疫防御作用,其机制可能与降低巨噬细胞的炎症反应有关。 相似文献
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细菌生物被膜的耐药机制及控制策略 总被引:2,自引:0,他引:2
在特定的条件下,细菌可以形成生物被膜,包被有生物被膜的细菌称为被膜菌.被膜菌无论其形态结构、生理生化特性、致病性还是对环境因子的敏感性等都与浮游细菌有显著的不同,尤其对抗生素和宿主免疫系统具有很强的抵抗力,从而导致严重的临床问题,引起许多慢性和难治性感染疾病的反复发作.细菌生物被膜粘附在各种医疗器械及导管上极难清除,以至引发大量的医源性感染.近年来,随着人们对细菌致病机制认识的逐步深入,控制细菌生物被膜的方法已有较大发展.本文拟探讨被膜菌的耐药机制并着重综述细菌生物被膜控制方法的最新研究进展. 相似文献
4.
肺炎克雷伯菌生物被膜的体外模型建立 总被引:1,自引:0,他引:1
目的研究临床分离的肺炎克雷伯菌在体外形成生物被膜的情况,为进一步研究生物被膜肺炎克雷伯菌的耐药机制奠定基础。方法采用改良平板法建立肺炎克雷伯菌生物被膜模型,用喷金法和扫描电镜观察鉴定,并对生物被膜的形成进行定量分析。结果23株临床分离的肺炎克雷伯菌菌株生物被膜形成能力不同,以强阳性生物被膜形成能力者为最多数。结论绝大多数临床分离的肺炎克雷伯菌菌株具有较强的生物被膜形成能力。应用改良平板法能够较好的在体外建立其生物被膜模型。 相似文献
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作为人类条件性感染的前三大病原菌之一的铜绿假单胞菌,是一种革兰氏阴性细菌,对免疫功能低下和囊性纤维化患者可以造成严重和持续性感染。造成这种持续感染的原因主要是由于细菌接收外界信号后,在自身调控网络的协同作用下,会依附于固体表面,并产生胞外多糖、基质蛋白和胞外DNA等大分子物质形成高度结构化的膜状复合物将自身包裹形成生物被膜群体结构。生物被膜可以有效帮助细菌定殖、提高细菌对抗菌物质和宿主免疫反应的抵抗能力、促进群落细菌的细胞-细胞之间的信号交流等,是临床治疗中病原菌慢性感染和反复感染最重要的原因之一。本篇综述重点介绍了铜绿假单胞菌生物被膜的各组成成分及其在生物被膜形成中的重要功能,并进一步阐述了群体感应系统(las、rhl、pqs与iqs)和c-di-GMP对铜绿假单胞菌生物被膜形成的调控作用。通过本篇综述可以更清晰地了解细菌生物被膜形成和调控的过程,为开发新的治疗生物被膜感染策略提供帮助。 相似文献
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大量研究报道生物被膜细菌对抗生素的耐药性是浮游菌的10–1 000倍,据报道细菌生物被膜是80%以上细菌感染的罪魁祸首,对医疗保健领域构成了严峻的挑战。植物提取物及其活性成分对细菌生物被膜有明显的抑制作用,包括减少生物被膜量、生物被膜活菌数以及清除已经成熟的生物被膜等。该文对这些有效的植物提取物及其活性成分进行了总结,并分析了其抗细菌生物被膜的作用机制。旨在为防治细菌生物被膜感染的植物类药物的开发提供参考。 相似文献
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大肠埃希菌(Escherichia coli)是一种兼性厌氧、有鞭毛的革兰氏阴性短杆菌,常寄生于人和动物肠道内,是常见的人畜共患病病原之一。大肠埃希菌易形成生物被膜,这是一种由细菌群落分泌能够包裹自身的胞外基质与细菌结合形成的特殊聚集体,也是临床细菌感染疾病难以治愈的主要原因。生物被膜的形成不仅帮助细菌逃避宿主的防御系统,还可以降低或阻止药物发挥作用,从而诱发生物被膜相关感染(biofilm-associated infections, BAI)。本文从生物被膜形成的基因调控系统和相关调控蛋白等角度,归纳总结调控大肠埃希菌生物被膜形成的分子机制,并对防治BAI的策略进行了概述,为寻找合适的药物靶点以及防治BAI提供参考。 相似文献
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目的通过阴离子表面活性剂十二烷基苯磺酸钠针对表皮葡萄球菌生物被膜菌黏附抑制作用的研究,为临床抗表皮葡萄球菌生物被膜菌引起的相关感染探索新的研究方向和可能的治疗途径。方法以红霉素为阳性对照,利用XTT减低法评价十二烷基苯磺酸钠对表皮葡萄球菌初始黏附的影响。结果十二烷基苯磺酸钠在1 000、100mg/L浓度下对表皮葡萄球菌初始黏附均有抑制作用;以浓度为1 000mg/L十二烷基苯磺酸钠对实验材料进行预处理,对表皮葡萄球菌初始黏附有明显抑制作用。结论阴离子表面活性剂十二烷基苯磺酸钠在特定浓度下对表皮葡萄球菌产生物被膜菌的初始黏附有抑制作用。 相似文献
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【目的】为比较反式和顺式肉桂醛对肉源假单胞菌生物被膜和致腐性的影响。【方法】通过平板计数测定两种肉桂醛对隆德假单胞菌的最小抑菌浓度(MIC),结晶紫法、珠涡流法、激光共聚焦显微镜观察、福林法等检测亚抑菌浓度肉桂醛处理下隆德假单胞菌生物被膜形成、运动性和胞外酶活性变化。荧光定量RT-PCR检测肉桂醛对隆德假单胞菌粘附lapA、鞭毛fliC、蛋白酶aprX和脂肪酶lip基因表达量的影响。【结果】反式和顺式肉桂醛对隆德假单胞菌的MIC分别为200μg/mL和225μg/mL,1/8 MIC、1/4MIC、1/2MIC亚抑菌浓度肉桂醛显著降低隆德假单胞菌生物被膜结晶紫和粘附性,其中1/2MIC反式和顺式肉桂醛处理下被膜分别减少60.27%和52.05%,菌体粘附降低56.35%和61.10%。亚抑菌浓度肉桂醛显著减少被膜厚度,反式肉桂醛还能显著杀灭被膜菌。且肉桂醛能显著抑制菌体的泳动性,反式肉桂醛对生物被膜和泳动性的抑制效果更强。肉桂醛还能抑制隆德假单胞菌蛋白酶和脂肪酶活性,其中1/2MIC反式和顺式肉桂醛处理下菌体蛋白酶分别减少61.90%和76.19%,脂肪酶降低40.17%和47.01%。且发现肉桂醛显著降低lapA、fliC、aprX和lip表达量,其中1/2MIC反式和顺式肉桂醛分别降低4个基因表达量至对照组的0.05–0.16和0.02–0.12倍。【结论】两种亚抑菌浓度肉桂醛异构体显著抑制隆德假单胞菌生物被膜和致腐性,其中反式肉桂醛对生物被膜抑制较强,而顺式肉桂醛更有效地降低致腐酶活性,其与肉桂醛下调相应基因表达密切相关。 相似文献
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细菌分泌胞外多糖附着在物体表面组成一个结构性群体即生物膜,导致对抗生素的强抵抗性和感染的迁延不愈。反过来,已形成的生物膜也可以分散为游离菌,许多环境物质能够促进该分散过程,并且这些物质与抗生素合用对生物膜有强大的对抗作用。从生物膜到浮游菌是个复杂的过程,目前关于铜绿假单胞菌生物膜分散的特征、机制、诱导分子等已经引起了学者的强烈兴趣,随着问题的深入研究必然会给人类治疗生物膜所致的难治性感染带来更大的意义。 相似文献
12.
Barraud N Hassett DJ Hwang SH Rice SA Kjelleberg S Webb JS 《Journal of bacteriology》2006,188(21):7344-7353
Bacterial biofilms at times undergo regulated and coordinated dispersal events where sessile biofilm cells convert to free-swimming, planktonic bacteria. In the opportunistic pathogen Pseudomonas aeruginosa, we previously observed that dispersal occurs concurrently with three interrelated processes within mature biofilms: (i) production of oxidative or nitrosative stress-inducing molecules inside biofilm structures, (ii) bacteriophage induction, and (iii) cell lysis. Here we examine whether specific reactive oxygen or nitrogen intermediates play a role in cell dispersal from P. aeruginosa biofilms. We demonstrate the involvement of anaerobic respiration processes in P. aeruginosa biofilm dispersal and show that nitric oxide (NO), used widely as a signaling molecule in biological systems, causes dispersal of P. aeruginosa biofilm bacteria. Dispersal was induced with low, sublethal concentrations (25 to 500 nM) of the NO donor sodium nitroprusside (SNP). Moreover, a P. aeruginosa mutant lacking the only enzyme capable of generating metabolic NO through anaerobic respiration (nitrite reductase, DeltanirS) did not disperse, whereas a NO reductase mutant (DeltanorCB) exhibited greatly enhanced dispersal. Strategies to induce biofilm dispersal are of interest due to their potential to prevent biofilms and biofilm-related infections. We observed that exposure to SNP (500 nM) greatly enhanced the efficacy of antimicrobial compounds (tobramycin, hydrogen peroxide, and sodium dodecyl sulfate) in the removal of established P. aeruginosa biofilms from a glass surface. Combined exposure to both NO and antimicrobial agents may therefore offer a novel strategy to control preestablished, persistent P. aeruginosa biofilms and biofilm-related infections. 相似文献
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Should we stay or should we go: mechanisms and ecological consequences for biofilm dispersal 总被引:3,自引:0,他引:3
McDougald D Rice SA Barraud N Steinberg PD Kjelleberg S 《Nature reviews. Microbiology》2012,10(1):39-50
In most environments, bacteria reside primarily in biofilms, which are social consortia of cells that are embedded in an extracellular matrix and undergo developmental programmes resulting in a predictable biofilm 'life cycle'. Recent research on many different bacterial species has now shown that the final stage in this life cycle includes the production and release of differentiated dispersal cells. The formation of these cells and their eventual dispersal is initiated through diverse and remarkably sophisticated mechanisms, suggesting that there are strong evolutionary pressures for dispersal from an otherwise largely sessile biofilm. The evolutionary aspect of biofilm dispersal is now being explored through the integration of molecular microbiology with eukaryotic ecological and evolutionary theory, which provides a broad conceptual framework for the diversity of specific mechanisms underlying biofilm dispersal. Here, we review recent progress in this emerging field and suggest that the merging of detailed molecular mechanisms with ecological theory will significantly advance our understanding of biofilm biology and ecology. 相似文献
14.
Many biofilm populations are known for their exceptional biodiversity, but the relative contributions of the forces that could produce this diversity are poorly understood. This uncertainty grows in the old, well-established communities found on many natural surfaces and in long-term, chronic infections. If the prevailing interactions among species within biofilms are positive, productivity should increase with diversity, but if they tend towards competition or antagonism, productivity should decrease. Here, we describe the parallel evolution of synergistic communities derived from a clone of Burkholderia cenocepacia during ∼1500 generations of biofilm selection. This long-term evolution was enabled by a new experimental method that selects for daily cycles of colonization, biofilm assembly and dispersal. Each of the six replicate biofilm populations underwent a common pattern of adaptive morphological diversification, in which three ecologically distinct morphotypes arose in the same order of succession and persisted. In two focal populations, mixed communities were more productive than any monoculture and each variant benefited from the mixture. These gains in output resulted from asymmetrical cross-feeding between ecotypes and the expansion and partitioning of biofilm space that constructed new niches. Therefore, even in the absence of starting genetic variation, prolonged selection for surface colonization generates a dynamic of ecological succession that enhances productivity. 相似文献
15.
Nicolas Barraud Michael V. Storey Zoe P. Moore Jeremy S. Webb Scott A. Rice Staffan Kjelleberg 《Microbial biotechnology》2009,2(3):370-378
Strategies to induce biofilm dispersal are of interest due to their potential to prevent biofilm formation and biofilm‐related infections. Nitric oxide (NO), an important messenger molecule in biological systems, was previously identified as a signal for dispersal in biofilms of the model organism Pseudomonas aeruginosa. In the present study, the use of NO as an anti‐biofilm agent more broadly was assessed. Various NO donors, at concentrations estimated to generate NO levels in the picomolar and low nanomolar range, were tested on single‐species biofilms of relevant microorganisms and on multi‐species biofilms from water distribution and treatment systems. Nitric oxide‐induced dispersal was observed in all biofilms assessed, and the average reduction of total biofilm surface was 63%. Moreover, biofilms exposed to low doses of NO were more susceptible to antimicrobial treatments than untreated biofilms. For example, the efficacy of conventional chlorine treatments at removing multi‐species biofilms from water systems was increased by 20‐fold in biofilms treated with NO compared with untreated biofilms. These data suggest that combined treatments with NO may allow for novel and improved strategies to control biofilms and have widespread applications in many environmental, industrial and clinical settings. 相似文献
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Biofilms are differentiated masses of microbes that form on surfaces and are surrounded by an extracellular matrix. Fungal biofilms, especially those of the pathogen Candida albicans, are a cause of infections associated with medical devices. Such infections are particularly serious because biofilm cells are relatively resistant to many common antifungal agents. Several in vitro models have been used to elucidate the developmental stages and processes required for C. albicans biofilm formation, and recent studies have begun to define biofilm genetic control. It is clear that cell-substrate and cell-cell interactions, hyphal differentiation and extracellular matrix production are key steps in biofilm development. Drug resistance is acquired early in biofilm formation, and appears to be governed by different mechanisms in early and late biofilms. Quorum sensing might be an important factor in dispersal of biofilm cells. The past two years have seen the emergence of several genomic strategies to uncover global events in biofilm formation and directed studies to understand more specific events, such as hyphal formation, in the biofilm setting. 相似文献
18.
The formation of the organized bacterial community called biofilm is a crucial event in bacterial physiology. Given that biofilms are often refractory to antibiotics and disinfectants to which planktonic bacteria are susceptible, their formation is also an industrially and medically relevant issue. Pseudomonas aeruginosa, a well-known human pathogen causing acute and chronic infections, is considered a model organism to study biofilms. A large number of environmental cues control biofilm dynamics in bacterial cells. In particular, the dispersal of individual cells from the biofilm requires metabolic and morphological reprogramming in which the second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) plays a central role. The diatomic gas nitric oxide (NO), a well-known signaling molecule in both prokaryotes and eukaryotes, is able to induce the dispersal of P. aeruginosa and other bacterial biofilms by lowering c-di-GMP levels. In this review, we summarize the current knowledge on the molecular mechanisms connecting NO sensing to the activation of c-di-GMP-specific phosphodiesterases in P. aeruginosa, ultimately leading to c-di-GMP decrease and biofilm dispersal. 相似文献
19.
Gareth LuTheryn Peter Glynne-Jones Jeremy S Webb Dario Carugo 《Microbial biotechnology》2020,13(3):613-628
Bacterial biofilms are an ever-growing concern for public health, featuring both inherited genetic resistance and a conferred innate tolerance to traditional antibiotic therapies. Consequently, there is a growing interest in novel methods of drug delivery, in order to increase the efficacy of antimicrobial agents. One such method is the use of acoustically activated microbubbles, which undergo volumetric oscillations and collapse upon exposure to an ultrasound field. This facilitates physical perturbation of the biofilm and provides the means to control drug delivery both temporally and spatially. In line with current literature in this area, this review offers a rounded argument for why ultrasound-responsive agents could be an integral part of advancing wound care. To achieve this, we will outline the development and clinical significance of biofilms in the context of chronic infections. We will then discuss current practices used in combating biofilms in chronic wounds and then critically evaluate the use of acoustically activated gas microbubbles as an emerging treatment modality. Moreover, we will introduce the novel concept of microbubbles carrying biologically active gases that may facilitate biofilm dispersal. 相似文献
20.
Medical device-associated infections involve the attachment of cells to a surface, production of an extracellular matrix and development of a mature biofilm. Many Candida albicans disease states involve biofilm growth. These infections have great impact on public health because organisms in biofilms exhibit dramatically reduced susceptibility to antifungal therapy. Progression to a mature biofilm is dependent on cell adhesion, extracellular matrix production and the yeast-to-hyphae transition. Numerous in vitro biofilm model systems have been successfully used to examine biofilm architecture, development, cell phenotypes and drug resistance. Although these studies have included a number of experimental variables to mimic infections in patients, it is difficult to accurately account for the multitude of host and infection-site variables that are probably important in humans. Recent studies have begun to explore C. albicans biofilms using animal biofilm infection models in order to more completely reflect the complexity of this host-fungal interaction. 相似文献