Effect of innate honey components on microbial stress. Understanding the mechanism of honey antibacterial action against anaerobe bacteria associated

蜂蜜在伤口治疗方面有着悠久的历史，其治疗特性主要归因于酶促产生过氧化氢(H_2O_2)、高渗透压、低pH(3.2-4.5)以及其他天然抗菌化合物的贡献。在医用蜂蜜(麦卢卡、中蜂蜜、外科蜂蜜、雷马韦)上市后，蜂蜜重新引起了人们对其临床潜力的兴趣，因为据报道，它对广泛的临床重要病原体具有抗菌/杀菌活性。蜂蜜的潜在抗菌机制的调查仍然不清楚，构成了这项研究的目的。将开发和优化具有高抗菌活性的模型蜂蜜，以表征与阴道感染相关的大肠杆菌菌株的抗菌机制。进一步的假设涉及蜂蜜和乳杆菌的潜在协同作用，它们产生过氧化氢，抑制阴道中厌氧菌(和兼性厌氧菌)的定植。应用微生物学和分子生物学研究单独和协同应激(pH、渗透压、H_2O_2)对细菌反应的影响。显微镜技术将阐明多重胁迫对细菌表型变化的影响。数学模型将支持细菌反应的预测。最终，系统地了解蜂蜜的抗菌作用和细菌应激反应的潜在分子机制对于开发创新的药物应用是至关重要的。这项前景看好的技术基于蜂蜜抗菌成分在阴道内的控制释放机制，消除了病原体的定植，并将微生物群保持在理想的水平。

Honey has a long history in wound treatment, proved to have therapeutic properties mainly attributed to the enzymatic production of hydrogen peroxide (H2O2), high osmolality, low pH (3.2-4.5) and also the contribution of other innate antibacterial compounds. After the availability of medical grade honeys (Manuka, Medihoney, Surgihoney, Remavil) on the market, honey garnered renewed interest in its clinical potential as it was reported to have antibacterial/ bactericidal activity against a wide range of clinical important pathogens. The investigation of the underlying antimicrobial mechanism of honey, being still obscure, constitutes the aim of this study. A model- honey, which performs high antibacterial activity, will be developed and optimized, so as to be characterized the antibacterial mechanism against E.coli strains associated with vaginal infection. Further hypothesis concern the potential synergistic effect of honey and Lactobacilli, which produce H2O2, inhibiting the colonization of anaerobes (and facultative anaerobes) in the vagina. The effect of individual and synergistic stress (pH, osmolality, H2O2) on bacteria responses will be investigated with applied microbiology and molecular biology. Microscopy techniques will elucidate the effect of multiple stresses on bacteria phenotype changes. Mathematical models will support the prediction of bacterial responses. Ultimately, the systematic understanding of honey antibacterial action and the underlying molecular mechanism on bacterial stress responses is pivotal for the development of an innovative pharmaceutical application. This promising technology is based on the controlled release mechanism of honey antibacterial components intravaginally, eliminating pathogens' colonization and maintaining the microflora in desirable levels.