Pacheco Paulo Anastácio Furtado, Jansen Charlotte Uldahl, Rybtke Morten, Tolker-Nielsen Tim, Qvortrup Katrine
Department of Chemistry, Technical University of Denmark Lyngby Denmark
Department of Immunology and Microbiology, Costerton Biofilm Center, University of Copenhagen Copenhagen Denmark.
RSC Med Chem. 2025 Jul 18. doi: 10.1039/d5md00272a.
, a Gram-positive bacterium, is a pathogen capable of infecting nearly all host tissues, causing severe morbidity and mortality. Antibiotic resistant are abundant, and multidrug resistant strains are emerging worldwide. The emergence and spread of antibiotic resistant bacterial strains is a growing public health concern, and new approaches are urgently needed to combat this threat. One promising strategy is to develop so-called 'antipathogenic' drugs, which acts by blocking bacterial virulence factors. produces an array of virulence factors that enhance bacterium survival and spreading in the host by degrading host tissue, liberating nutrients from the host, and evading host immune responses. In contrast to antibiotics, antipathogenic drugs do not kill bacteria or stop their growth and are assumed not to impose a strong selection for resistance traits. Thus, by targeting virulence factors, it may be possible to reduce the severity of bacterial infections, giving the immune system an upper hand, without promoting the development of resistance. This review describes work done on developing small molecules that target three virulence categories: pore-forming toxins, immune evasion, and quorum sensing. We discuss the structure-activity relationships (SAR) of the various compounds investigated, focusing on their mechanisms of action and therapeutic potential. The review highlights the potential of targeting virulence factors as a promising strategy to combat antibiotic resistant infections, and suggests directions for further research to identify new compounds with improved efficacy.
作为一种革兰氏阳性菌，是一种能够感染几乎所有宿主组织、导致严重发病和死亡的病原体。抗生素耐药菌大量存在，且多重耐药菌株在全球范围内不断出现。抗生素耐药细菌菌株的出现和传播是一个日益严重的公共卫生问题，迫切需要新的方法来应对这一威胁。一种有前景的策略是开发所谓的“抗致病”药物，其作用方式是阻断细菌毒力因子。会产生一系列毒力因子，这些毒力因子通过降解宿主组织、从宿主中释放营养物质以及逃避宿主免疫反应来增强细菌在宿主体内的存活和传播能力。与抗生素不同，抗致病药物不会杀死细菌或阻止其生长，并且假定不会对耐药性状产生强烈的选择压力。因此，通过靶向毒力因子，有可能降低细菌感染的严重程度，使免疫系统占据上风，同时又不会促进耐药性的发展。本综述描述了在开发针对三种毒力类别（成孔毒素、免疫逃避和群体感应）的小分子方面所做的工作。我们讨论了所研究的各种化合物的构效关系（SAR），重点关注它们的作用机制和治疗潜力。该综述强调了靶向毒力因子作为对抗抗生素耐药感染的一种有前景策略的潜力，并为进一步研究以鉴定具有更高疗效的新化合物提出了方向。
