Lloyd David H
Department of Veterinary Clinical Sciences, Royal Veterinary College, Hawkshead Campus, North Mymms, Hertfordshire, UK.
Vet Dermatol. 2012 Aug;23(4):299-304, e59-60. doi: 10.1111/j.1365-3164.2012.01042.x. Epub 2012 Mar 12.
Growing antimicrobial resistance poses the threat that before long no suitable drugs will be available for treatment of common infections. This review examines promising new strategies for treatment and control of microbial diseases, with an emphasis on staphylococcal infection.
Advances in microbial genomics have provided tools identifying many new targets for antimicrobial drugs. Of particular interest amongst these are inhibition of microbial efflux pump activity, interruption or diversion of riboswitches controlling bacterial metabolism, and metagenomics, which allows analysis of genes from unculturable organisms.
Advances are also being made in biological systems for disease control, with the exploitation of antimicrobial peptides to attack micro-organisms and modulate immune responses, and the use of bacteriophages or their lysins to eliminate bacteria. There are new approaches in the development and targeting of vaccines and immunoglobulin preparations based on advanced knowledge of microbial physiology and immunoregulation.
With increasing recognition of the value of the normal microbiota in modulating immunity and the establishment of pathogens, there is growing interest in understanding the mammalian microbiome. Strategies are being developed to promote or maintain the normal microbiota, including the use of probiotics, and there is re-evaluation of the potential of bacterial interference.
Whilst these approaches are likely to generate new methods of disease control, few will yield usable products within the near future. There will be a continuing need for careful use of existing drugs based on firm diagnosis, rigorous hygiene and prudent antimicrobial stewardship.
日益增长的抗菌药物耐药性带来了一种威胁,即不久之后可能没有合适的药物可用于治疗常见感染。本综述探讨了治疗和控制微生物疾病的有前景的新策略,重点是葡萄球菌感染。
微生物基因组学的进展提供了工具,可识别许多新的抗菌药物靶点。其中特别值得关注的是抑制微生物外排泵活性、中断或改变控制细菌代谢的核糖开关,以及宏基因组学,它能分析来自不可培养生物的基因。
在疾病控制的生物系统方面也取得了进展,利用抗菌肽攻击微生物并调节免疫反应,以及使用噬菌体或其溶菌素来消除细菌。基于对微生物生理学和免疫调节的深入了解,在疫苗和免疫球蛋白制剂的开发及靶向方面有了新方法。
随着人们越来越认识到正常微生物群在调节免疫和病原体定植方面的价值,对了解哺乳动物微生物组的兴趣日益浓厚。正在制定促进或维持正常微生物群的策略,包括使用益生菌,并且正在重新评估细菌干扰的潜力。
虽然这些方法可能会产生新的疾病控制方法,但在不久的将来很少会产生可用的产品。基于明确的诊断、严格的卫生措施和审慎的抗菌药物管理,仍将持续需要谨慎使用现有药物。