Yssel A E J, Vanderleyden J, Steenackers H P
Centre of Microbial and Plant Genetics, Kasteelpark Arenberg 20, bus 2460, B-3001 Leuven, Belgium.
J Antimicrob Chemother. 2017 Aug 1;72(8):2156-2170. doi: 10.1093/jac/dkx151.
There is an urgent need for new antibacterial drugs that are robust against the development of resistance. Drug repurposing is a cost-effective strategy to fast-track the drug development process. Here we examine why the nucleoside and nucleobase analogue drugs in particular present an attractive class for repurposing. Some of these drugs have already been evaluated for their potential as antibacterial agents. In addition to inhibiting bacterial growth and survival, some also act synergistically with antibiotics, and as such can enhance the therapeutic spectrum of currently available antibiotics. Furthermore, nucleoside and nucleobase analogue drugs can inhibit bacterial virulence and biofilm formation. Biofilms are known to impart antibiotic tolerance and are associated with chronic infections. Targeting biofilm formation thus renders pathogens more susceptible to antibiotic treatment and host immune defences. Moreover, specific analogues have properties that make them less susceptible to the development of resistance. Thus, nucleoside and nucleobase analogue drugs ought to be considered as new weapons in our fight against pathogenic bacteria.
迫切需要能够有效抵御耐药性产生的新型抗菌药物。药物重新利用是加快药物研发进程的一种经济高效的策略。在此，我们探讨为何核苷和核碱基类似物药物尤其适合重新利用。其中一些药物已被评估其作为抗菌剂的潜力。除了抑制细菌生长和存活外，一些药物还能与抗生素协同作用，从而扩大现有抗生素的治疗范围。此外，核苷和核碱基类似物药物可抑制细菌毒力和生物膜形成。众所周知，生物膜会赋予细菌抗生素耐受性，并与慢性感染相关。因此，针对生物膜形成进行干预可使病原体更易受到抗生素治疗和宿主免疫防御的影响。此外，特定的类似物具有不易产生耐药性的特性。因此，核苷和核碱基类似物药物应被视为我们对抗病原菌的新武器。
