Dhusia Kalyani, Bajpai Archana, Ramteke P W
Deptartment of Computational Biology and Bioinformatics, Jacob Institute of Biotechnology and Bio-Engineering, Sam Higginbottom University of Agriculture, Technology and Sciences (SHUATS), Allahabad-211007 (U.P.), India.
Laboratory for Disease Systems Modeling, Center for Integrative Medical Sciences, RIKEN, Yokohama City, Kanagawa, 230-0045, Japan.
J Control Release. 2018 Jan 10;269:63-87. doi: 10.1016/j.jconrel.2017.11.001. Epub 2017 Nov 10.
Comparative study of siderophore biosynthesis pathway in pathogens provides potential targets for antibiotics and host drug delivery as a part of computationally feasible microbial therapy. Iron acquisition using siderophore models is an essential and well established model in all microorganisms and microbial infections a known to cause great havoc to both plant and animal. Rapid development of antibiotic resistance in bacterial as well as fungal pathogens has drawn us at a verge where one has to get rid of the traditional way of obstructing pathogen using single or multiple antibiotic/chemical inhibitors or drugs. 'Trojan horse' strategy is an answer to this imperative call where antibiotic are by far sneaked into the pathogenic cell via the siderophore receptors at cell and outer membrane. This antibiotic once gets inside, generates a 'black hole' scenario within the opportunistic pathogens via iron scarcity. For pathogens whose siderophore are not compatible to smuggle drug due to their complex conformation and stiff valence bonds, there is another approach. By means of the siderophore biosynthesis pathways, potential targets for inhibition of these siderophores in pathogenic bacteria could be achieved and thus control pathogenic virulence. Method to design artificial exogenous siderophores for pathogens that would compete and succeed the battle of intake is also covered with this review. These manipulated siderophore would enter pathogenic cell like any other siderophore but will not disperse iron due to which iron inadequacy and hence pathogens control be accomplished. The aim of this review is to offer strategies to overcome the microbial infections/pathogens using siderophore.
病原菌中铁载体生物合成途径的比较研究为抗生素和宿主药物递送提供了潜在靶点,这是计算可行的微生物治疗的一部分。利用铁载体模型获取铁是所有微生物中一种基本且成熟的模型,已知微生物感染会对动植物造成巨大破坏。细菌和真菌病原体中抗生素耐药性的迅速发展使我们处于一个必须摒弃使用单一或多种抗生素/化学抑制剂或药物来阻碍病原体的传统方法的边缘。“特洛伊木马”策略是对这一紧迫需求的回应,即抗生素通过细胞和外膜上的铁载体受体潜入致病细胞。这种抗生素一旦进入细胞,就会通过铁缺乏在机会性病原体中制造一种“黑洞”情况。对于那些由于其复杂构象和刚性价键而使铁载体无法携带药物的病原体,还有另一种方法。通过铁载体生物合成途径,可以实现抑制病原菌中铁载体的潜在靶点,从而控制病原菌的毒力。本综述还涵盖了为病原体设计人工外源铁载体的方法,这些铁载体将参与竞争并在摄取竞争中获胜。这些经过改造的铁载体将像其他铁载体一样进入致病细胞,但不会释放铁,从而导致铁缺乏,进而实现对病原体的控制。本综述的目的是提供利用铁载体克服微生物感染/病原体的策略。