Fabpharma c/oTioga venture, 336 Rue Saint Honoré, 75012 Paris, France.
Expert Opin Ther Pat. 2010 Oct;20(10):1401-18. doi: 10.1517/13543776.2010.511176.
The rising levels of antibiotic resistance in pathogenic microorganisms create an urgent need for new antimicrobial agents that are not affected by resistance mechanisms already present in the bacterial population. Targeting virulence is one of the alternative approaches to find new molecules to treat infections due to resistant bacteria. Novel strategies to identify these new antimicrobial agents have been reported.
A variety of virulence factors are now the target for inhibition mainly in the antibacterial field. This review focuses exclusively on the new virulence inhibitors published in patents (worldwide collection of patents filed) or in the literature since 2006.
New efficacy in vitro assays have been developed allowing screening of large numbers of molecules. These inhibitors are mainly antibacterial molecules, a few natural products, peptides and antibodies. A growing number of these published studies provide results showing a proof of concept with antivirulence compounds that were able to prevent or treat an infection in vivo. Moreover, some new antivirulence agents could inhibit virulence mechanisms that are common to different related pathogenic species, extending the potential spectrum of antivirulence compounds.
The progress reported recently for antivirulence molecules at the preclinical stages should allow new classes of molecules to enter into development as new antimicrobial agents with new mechanisms of action.
致病微生物中抗生素耐药性水平的上升,迫切需要新的抗菌药物,这些药物不应受细菌种群中已存在的耐药机制的影响。针对毒力是寻找治疗耐药菌感染的新分子的另一种方法。已经报道了一些新的策略来识别这些新的抗菌药物。
现在有多种毒力因子成为抑制的目标,主要在抗菌领域。本综述仅关注自 2006 年以来在专利(全球范围内提交的专利申请)或文献中发表的新的毒力抑制剂。
已经开发了新的体外功效测定方法,允许筛选大量的分子。这些抑制剂主要是抗菌分子、一些天然产物、肽和抗体。越来越多的这些已发表的研究提供了结果,表明具有抗毒力化合物的概念验证,这些化合物能够预防或治疗体内感染。此外,一些新的抗毒力药物可以抑制不同相关病原种属共有的毒力机制,从而扩大抗毒力化合物的潜在谱。
最近在临床前阶段报告的抗毒力分子的进展,应该允许新的分子类别作为具有新作用机制的新抗菌药物进入开发阶段。