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Evaluating and enhancing the activities of novel antimicrobials: Biomimetics, nanotechnology and natural compounds.

机译：评估和增强新型抗菌素的活性：仿生物，纳米技术和天然化合物。

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摘要

The recent finding as to the common distribution of antimicrobial peptides in multicellular organisms and their essential role in innate defenses has uncovered numerous possibilities for novel therapeutics. Despite the diversity of these peptides among organisms, investigations have revealed surprising similarities regarding their structure and their antimicrobial function. The insights gained from studies on antimicrobial peptides have provided new strategies and templates for the development and design of novel biomimetics that may be used in therapeutic, pharmaceutical and food applications. It is these features that are being used in the design of antimicrobially active peptide mimics in polymer and small molecule forms, some of which were investigated here for their broad spectrum activity alone and in combination with functional food ingredients (flavor and aroma compounds) capable of enhancing their activities. These novel combinations could be beneficial for targeted antimicrobial applications. The multicomponent systems developed here combine multiple functionalities -- the abilities of the biomimetic polymers to breach the gram-negative outer membrane and the activities of both components against the cell membrane, and possible targets within the cytoplasm. Because they act on the conserved structure of the cell membrane, these treatments may be difficult to surmount via developed resistance. The research reported here bridges the fields of not only polymer chemistry and microbiology, but also of natural products. As an example, the functional food ingredients used to enhance biomimetic polymer activities were sesquiterpenoids, a class of naturally occurring terpenes that are found in plants where they serve as defensive agents. These compounds, including bisabolol, farnesol and nerolidol have previously been shown to enhance the activities of traditional antimicrobials such as antibiotics (Brehm-Stecher and Johnson, 2003). Their additional ability to dramatically enhance the activities of biomimetic antimicrobial polymers was demonstrated in the present work.;Additional antimicrobial approaches were examined in this work, including the use of essential oils and metal nanoparticles. These compounds, either alone or in combination with enhancing compounds, were investigated with the aim of developing additional multicomponent antimicrobial systems. While essential oils have been used since ancient times for their antimicrobial properties, their use in some applications has been limited due to their strong odors and lack of effective activity at organoleptically acceptable levels. As a result, methods capable of enhancing their antimicrobial activities, especially in complex matrices, could be key to their advantageous use in food and clinical applications. Here, several different essential oils were combined with the polyionic compounds sodium polyphosphate and polyethylenimine and the activities of these systems were examined against a range of human pathogens. These polyions were found to be capable of potentiating the antimicrobial activities of the oils, allowing their effective use at lower levels.;Metals have also been shown to be broad-spectrum antimicrobial agents in both their ionic and macrometallic forms. While these forms have been used for millennia as antimicrobials, little is known about the activities of these metals in nanoparticulate form, an area of great interest given the rapid growth of the nanotechnology sector. Therefore, a series of metal nanoparticles, including several novel alloys, were evaluated for their antimicrobial activities and for their physical (binding) interactions with microbial cell surfaces. Results from this work suggest the potential for using commercial metal nanoparticle catalysts as novel antimicrobial compounds. These could be valuable as components of antimicrobially active surfaces or therapeutics, once potentially limiting safety issues of particle migration and toxicity are addressed.;Taken together, physical or chemical methods for enhancing the activities of core antimicrobials as diverse as biomimetic polymers, metal nanoparticles and essential oils or other natural compounds could provide beneficial strategies for developing effective multi-agent systems having enhanced antimicrobial properties. The resulting systems may find advantageous use in applications as diverse as food safety, environmental sanitation or clinical therapeutics.
机译：关于抗微生物肽在多细胞生物中的普遍分布及其在先天防御中的重要作用的最新发现，发现了新疗法的多种可能性。尽管这些肽在生物体中存在差异，但研究表明它们在结构和抗菌功能方面具有惊人的相似性。从抗微生物肽研究中获得的见识为开发和设计可用于治疗，药物和食品应用的新型仿生药物提供了新的策略和模板。正是这些特征被用于聚合物和小分子形式的抗微生物活性肽模拟物的设计中，此处仅对它们的广谱活性进行了研究，并与具有一定功能的食品成分（风味和香气化合物）结合使用，对其中一些进行了研究。增强他们的活动。这些新颖的组合可能对靶向抗菌应用有益。这里开发的多组分系统结合了多种功能-仿生聚合物突破革兰氏阴性外膜的能力以及这两种组分对细胞膜以及细胞质内可能靶标的活性。由于它们作用于细胞膜的保守结构，因此可能难以通过产生的耐药性克服这些治疗方法。本文报道的研究不仅在聚合物化学和微生物学领域，而且在天然产物领域都起到了桥梁作用。例如，用于增强仿生聚合物活性的功能性食品成分是倍半萜，这是一类天然存在的萜烯，可在植物中用作防御剂。这些化合物，包括比沙泊洛尔，法尼醇和奈洛尔醇，以前已被证明可以增强传统抗菌剂（例如抗生素）的活性（Brehm-Stecher和Johnson，2003）。在本工作中证明了它们具有显着增强仿生抗菌聚合物活性的附加能力。;在这项工作中还研究了其他抗菌方法，包括使用精油和金属纳米颗粒。为了开发另外的多组分抗微生物系统，对这些化合物单独或与增强化合物组合进行了研究。尽管自古以来就由于其抗菌性能而使用精油，但由于它们的强烈气味和感官上可接受的水平缺乏有效活性，因此其在某些应用中的使用受到限制。因此，能够增强其抗菌活性（尤其是在复杂基质中）的方法可能是其在食品和临床应用中的有利用途的关键。在这里，几种不同的精油与聚离子化合物多磷酸钠和聚乙烯亚胺混合，并针对多种人类病原体检测了这些系统的活性。发现这些聚离子能够增强油的抗微生物活性，使其在较低含量下有效使用。金属也已被证明是离子和大金属形式的广谱抗微生物剂。尽管这些形式已被用作抗微生物剂数千年，但对于纳米颗粒形式的这些金属的活性知之甚少，鉴于纳米技术领域的快速发展，这一领域引起了人们的极大兴趣。因此，评估了包括几种新型合金在内的一系列金属纳米颗粒的抗菌活性以及它们与微生物细胞表面的物理（结合）相互作用。这项工作的结果表明，使用市售金属纳米颗粒催化剂作为新型抗菌化合物的潜力。一旦解决了可能限制颗粒迁移和毒性的安全性问题，这些作为抗菌活性表面或治疗剂的成分就可能是有价值的。综合起来，物理或化学方法可增强诸如仿生聚合物，金属纳米颗粒和香精油或其他天然化合物可为开发具有增强抗菌性能的有效多剂系统提供有益的策略。所得的系统可以在食品安全，环境卫生或临床治疗等各种应用中找到有利的用途。

著录项

  • 作者

    Weinkauf, Heidi Ann.;

  • 作者单位

    Iowa State University.;

  • 授予单位 Iowa State University.;
  • 学科 Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 240 p.
  • 总页数 240
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 微生物学;
  • 关键词

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