趋磁细菌及磁小体的生物医学应用研究进展

近年来,趋磁细菌及其生物自身合成的磁小体由于良好的生物安全性逐渐被人们所认识,并被用于生物工程和医学应用研究。与人工化学合成磁性纳米颗粒相比,从趋磁细菌中提取的磁小体具有生物膜包被、生物相容性高、粒径均一及磁性高等优势。趋磁细菌因磁小体在其胞内呈链状排列,具有沿磁场方向泳动的能力,也被应用于各种应用研究。因此,综述了趋磁细菌及磁小体特性,并就最近的研究进展重点综述趋磁细菌和磁小体在生物工程及医学应用等领域的最新研究进展。     

趋磁细菌及其应用于生物导航的研究进展

趋磁性细菌是一种由于体内含有对磁场具有敏感性的磁小体,而能够沿着磁力线运动的特殊细菌,本文综述了趋磁细菌的分布、分类、特性、磁小体研究以及趋磁细菌在生物导航方面的研究进展.     

趋磁细菌的磁小体

趋磁细菌是一类对磁场有趋向性反应的细菌,其菌体能吸收外界环境中铁元素并在体内合成包裹有膜的纳米磁性颗粒Fe₃O₄或Fe₃O_{3S4晶体即磁小体。综述了趋磁细菌的磁小体生物矿化的条件,以及趋磁细菌的铁离子吸收、磁小体囊泡的形成、铁离子的转运到磁小体囊泡及囊泡中受控的Fe3O4生物矿化的分子生物学和生物化学等方面的研究进展,重点介绍了趋磁细菌磁小体合成机制的研究进展及未来研究磁小体的发展方向。}     

趋磁细菌磁小体合成机制研究进展

趋磁细菌可在环境中吸收大量铁并在细胞内合成纳米级磁性颗粒—磁小体。比较几种趋磁细菌基因组特征,针对磁小体岛及与磁小体合成相关基因功能特点等方面,综述了当前磁小体合成机制的研究进展。     

趋磁细菌及磁小体在肿瘤治疗中的应用

提高抗肿瘤药物的靶向性是肿瘤治疗、降低药物副作用的重要手段。在肿瘤组织内部由于癌细胞的快速增殖致使其形成低氧区,低氧区会对多种肿瘤治疗方案产生耐受。趋磁细菌 (Magnetotactic bacteria, MTB) 是一类能在细胞内产生外包生物膜、纳米尺寸、单磁畴磁铁矿 (Fe3O4) 或硫铁矿 (Fe3S4) 晶体颗粒-磁小体的微生物的统称。在磁场的作用下,趋磁细菌可凭借鞭毛运动至厌氧区。趋磁细菌在动物体内毒性较低且生物相容性良好,其磁小体与人工合成的磁性纳米材料相比优势显著。文中在介绍趋磁细菌及其磁小体生物学特点、理化性能的基础上,综述了趋磁细菌作为载体偶联药物进入肿瘤内部,并通过感受低氧信号定位于肿瘤低氧区,以及趋磁细菌竞争肿瘤细胞铁源的研究进展,总结了磁小体运载化疗药物、抗体、DNA疫苗靶向结合肿瘤的研究进展,分析了趋磁细菌及磁小体肿瘤治疗中面临的问题,并对趋磁细菌和磁小体在肿瘤治疗中的应用进行了展望。     

趋磁细菌概述及应用进展

趋磁细菌是一类具有趋磁行为的革兰氏阴性茵的统称,其趋磁特性是由于菌体内含有磁小体。磁小体是由膜包被的纳米尺寸单磁畴颗粒,在菌体内多呈链状排列。自被发现以来,趋磁细菌及磁小体已逐步成为新的生物资源被广泛研究于材料学、医学、生物学、物理学、地质学等多个学科领域,并在仿生学、生态学、医学、地质学、工业处理、卫生检验等多个领域得到应用。主要介绍了趋磁细菌的生物特征、研究发展进程,以及近年来在多个学科领域的研究与应用。     

细菌纳米磁小体有望作为靶向药物载体

趋磁细菌细胞内合成的纳米磁小体具有颗粒均匀,晶型稳定的特点,每个磁小体有脂膜包被。提纯的磁小体毒性低,生物相容性好,可作为多种药物和大分子化合物的载体而应用于定向治疗肿瘤。本文介绍了细菌磁小体的结构特点,提出了采用细菌磁小体连接抗癌药物的策略,讨论了建立磁小体载药体系靶向治疗癌症的可能性。     

趋磁细菌及磁小体研究的回顾和展望

趋磁细菌及磁小体研究的回顾和展望陈明杰,卫扬保（武汉大学生命科学学院微生物学与免疫学系．武汉４３００７２）一趋磁细菌研究现状１趋磁细菌的发现１９７５年,美国人Ｂｌａｋｅｍｏｒｅ在显微镜下观察湖泊底部污泥的富集样品时,发现有一类细菌总是聚集在视野的靠北...     

趋磁螺菌中磁小体链装配相关基因及其功能

趋磁细菌(MTB)依赖于体内磁小体结构在磁场中取向,多个磁小体以一定的组 织形式排列是形成菌体内生物磁罗盘的重要环节．多数趋磁细菌中磁小体成链排列,有效增加了细胞磁偶极矩,从而使菌体表现出在环境磁场中定向的能力．趋磁螺菌M. magneticum AMB－1和M. gryphiswaldense MSR－1中磁小体均沿细胞长轴形成一条磁 小体链．通过对相关基因突变体表型的研究,结合对磁小体链形成过程的实时动态观 察,人们已初步了解MamJ、MamK和MamA等基因在磁小体链装配和维护过程中的功能．本文介绍了近年来趋磁螺菌磁小体链装配过程中重要功能性基因的研究进展,并重点分析了AMB-1和MSR-1中磁小体链装配的差异．     

趋磁细菌多样性与应用研究进展 *

趋磁细菌是一类可以沿磁场方向进行运动的微生物统称,在细胞内合成由生物膜包被、链状排列、纳米级、单磁畴的磁铁矿 (Fe₃O₄) 或胶黄铁矿 (Fe₃S₄) 的磁小体颗粒。趋磁细菌在自然界分布广泛且多样性丰富,不仅在水环境和沉积环境的铁、硫、碳、氮、磷等元素生物地球化学循环中发挥重要作用,而且在污染治理、疾病诊断和治疗等方面有较好的应用。趋磁细菌磁小体由生物膜包被并在细胞调控下合成,是一类新型的生物源磁性纳米材料。相比常规化学合成的磁性纳米颗粒,磁小体具有大小均一、生物相容性高、兼具化学修饰和基因工程修饰功能等特点,在磁性分离、固定化酶、食品检测、环境监测、医学诊断、磁共振成像、磁热疗和靶向治疗等方面具有广阔的应用前景。在介绍趋磁细菌多样性研究的基础上,综述了趋磁细菌和磁小体的制备、修饰及其应用的最新进展,并对未来的研究进行了展望。     

磁分离仪分离磁性细菌的新方法

磁性细菌胞内可以产生磁性颗粒,因此具有趋磁性,基于这种特性,利用磁分离的原理,本研究开发了一种磁性细菌分离仪,提供了一种分离磁性细菌的新方法。以氧化亚铁硫杆菌为例,使用磁性细菌分离仪进行分离,可以得到强磁菌和弱磁菌。利用透射电镜观察,强磁菌胞内磁性颗粒明显多于弱磁菌;半固体平板磁泳实验也表明强磁菌趋磁性明显强于弱磁菌。各项实验结果表明磁性细菌分离仪可以有效地分离磁性细菌,这是一种分离磁性细菌的新方法,将促进磁性细菌分离培养的研究。     

A new study of bacterial motion: superconducting quantum interference device microscopy of magnetotactic bacteria.

The recently developed "microscope" based on a high-Tc dc SQUID (superconducting quantum interference device) is used to detect the magnetic fields produced by the motion of magnetotactic bacteria, which have permanent dipole moments. The bacteria, in growth medium at room temperature, can be brought to within 15 micron of a SQUID at liquid nitrogen temperature. Measurements are performed on both motile and nonmotile bacteria. In the nonmotile case, we obtain the power spectrum of the magnetic field noise produced by the rotational Brownian motion of the ensemble of bacteria. Furthermore, we measure the time-dependent field produced by the ensemble in response to an applied uniform magnetic field. In the motile case, we obtain the magnetic field power spectra produced by the swimming bacteria. Combined, these measurements determine the average rotational drag coefficient, magnetic moment, and the frequency and amplitude of the vibrational and rotational modes of the bacteria in a unified set of measurements. In addition, the microscope can easily resolve the motion of a single bacterium. This technique can be extended to any cell to which a magnetic tag can be attached.     

Magnetic susceptibility of microorganisms.

Total magnetic susceptibility of 13 species and varieties of bacteria was investigated using the relative method of Guy. It has been established that the index of magnetic susceptibility is a constant characteristic of bacteria. Total magnetic susceptibility ranged from --0.3295.10(-6) in Escherichia P678 to --0.4965.10(-6) in Proteus. It has also been established that magnetic susceptibility changes during long-term passages of bacteria in fluctuating +/- 0.1 Oe) magnetic field. This is suggestive of a low threshold of their magnetic susceptibility and permits a rough assessment of the importance of fluctuations of the geomagnetic field for the viability of microbes.     

Use of magnetic particles isolated from magnetotactic bacteria for enzyme immobilization

Summary We report the novel use of magnetic particles isolated from magnetotactic bacteria. Magnetotactic bacteria were collected from enriched sludge by use of a magnetic harvesting apparatus. Magnetic particles separated from magnetotactic bacteria were shown to be pure magnetite. Glucose oxidase and uricase were immobilized on magnetic particles. The activity of glucose oxidase immobilized on biogenic magnetites was 40 times that immobilized on artificial magnetites or Zn-ferrite particles. Both glucose oxidase and uricase coupled with biogenic magnetic particles retained their activities when they were reused 5 times.     

Effect of super high magnetic field on the growth ofEscherichia coli

Summary Auxotrophic mutants ofEscherichia coli were grown under the super high magnetic field (11.7 Tesla) and the effect of the field both on the growth and mutation frequency of the bacteria was investigated. When the bacteria were cultivated in complex media, the growth was stimulated under 11.7T in comparison with that in geomagnetic field. When the bacteria were grown in synthetic media, the growth rates were reduced significantly. Neither mutagenic nor lethal effects of the magnetic field on the bacteria was observed. A potential application of high magnetic strength as a controlling factor of the bacterial growth was implied.     

Quantifying the magnetic advantage in magnetotaxis

Magnetotactic bacteria are characterized by the production of magnetosomes, nanoscale particles of lipid bilayer encapsulated magnetite, that act to orient the bacteria in magnetic fields. These magnetosomes allow magneto-aerotaxis, which is the motion of the bacteria along a magnetic field and toward preferred concentrations of oxygen. Magneto-aerotaxis has been shown to direct the motion of these bacteria downward toward sediments and microaerobic environments favorable for growth. Herein, we compare the magneto-aerotaxis of wild-type, magnetic Magnetospirillum magneticum AMB-1 with a nonmagnetic mutant we have engineered. Using an applied magnetic field and an advancing oxygen gradient, we have quantified the magnetic advantage in magneto-aerotaxis as a more rapid migration to preferred oxygen levels. Magnetic, wild-type cells swimming in an applied magnetic field more quickly migrate away from the advancing oxygen than either wild-type cells in a zero field or the nonmagnetic cells in any field. We find that the responses of the magnetic and mutant strains are well described by a relatively simple analytical model, an analysis of which indicates that the key benefit of magnetotaxis is an enhancement of a bacterium's ability to detect oxygen, not an increase in its average speed moving away from high oxygen concentrations.     

Use of magnetic beads for Gram staining of bacteria in aqueous suspension.

A Gram staining technique was developed using monodisperse magnetic beads in concentrating bacteria in suspension for downstream application. The technique does not require heat fixation of organisms, electrical power, or a microscope. Gram-negative and Gram-positive bacteria were identified macroscopically based on the colour of the suspension. The bacteria concentrated on magnetic beads may also be identified microscopically.     

Reduced Efficiency of Magnetotaxis in Magnetotactic Coccoid Bacteria in Higher than Geomagnetic Fields

Magnetotactic bacteria are microorganisms that orient and migrate along magnetic field lines. The classical model of polar magnetotaxis predicts that the field-parallel migration velocity of magnetotactic bacteria increases monotonically with the strength of an applied magnetic field. We here test this model experimentally on magnetotactic coccoid bacteria that swim along helical trajectories. It turns out that the contribution of the field-parallel migration velocity decreases with increasing field strength from 0.1 to 1.5 mT. This unexpected observation can be explained and reproduced in a mathematical model under the assumption that the magnetosome chain is inclined with respect to the flagellar propulsion axis. The magnetic disadvantage, however, becomes apparent only in stronger than geomagnetic fields, which suggests that magnetotaxis is optimized under geomagnetic field conditions. It is therefore not beneficial for these bacteria to increase their intracellular magnetic dipole moment beyond the value needed to overcome Brownian motion in geomagnetic field conditions.     

趋磁细菌运动特性的研究进展

细菌的运动性是影响其生存及致病的一个关键条件,同时也为合成和开发仿生运动体、微型机器人等提供了有效的模型。趋磁细菌具有胞内磁小体从而能够感知磁场的变化,进而影响其运动行为。目前,这种外部磁场与生物体的远程响应模式已在环境、医疗、材料等领域有广泛应用。因此,聚焦于趋磁细菌的运动特性,综述了趋磁细菌运动行为的表征、运动机理以及应用等方面的最新研究进展,并对该领域的发展和面临的挑战进行了展望。