Laboratory of Medical Microbiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370 Wrocław, Poland.
Int J Mol Sci. 2021 Jun 23;22(13):6762. doi: 10.3390/ijms22136762.
is an opportunistic human pathogen that has become a nosocomial health problem worldwide. The pathogen has multiple drug removal and virulence secretion systems, is resistant to many antibiotics, and there is no commercial vaccine against it. is a zoonotic pathogen that is on the Select Agents list. The bacterium is the deadliest pathogen known to humans and antibiotic-resistant strains are appearing naturally. There is no commercial vaccine against the pathogen, either. In the current work, novel compounds based on metallacarborane cage were studied on strains of and a substitute, . The representative compounds had IC values below 10 µM against and values of 20-50 μM against . Artificial generation of compound-resistant suggested a common mechanism for drug resistance, the first reported in the literature, and suggested -linked metallacarboranes as impervious to cellular mechanisms of resistance generation. SEM analysis of the compound-resistant strains showed that the compounds had a predominantly bacteriostatic effect and blocked bacterial cell division in . The compounds could be a starting point towards novel anti- drugs and the strategy presented here proposes a mechanism to bypass any future drug resistance in bacteria.
是一种机会性病原体，已成为全球医院感染的健康问题。该病原体具有多种药物去除和毒力分泌系统，对许多抗生素具有耐药性，并且没有针对它的商业疫苗。 是一种人畜共患病原体，在选择剂清单上。该细菌是已知对人类最致命的病原体，并且具有耐药性的菌株正在自然出现。也没有针对该病原体的商业疫苗。在目前的工作中，研究了基于金属碳硼烷笼的新型化合物对 和替代物 的菌株。代表性化合物对 的 IC 值低于 10µM，对 的值为 20-50µM。人工生成的化合物耐药 表明存在一种共同的耐药机制，这是文献中首次报道的，并表明 -连接的金属碳硼烷对耐药性产生的细胞机制具有不可渗透性。化合物耐药菌株的 SEM 分析表明，该化合物主要具有抑菌作用，并阻断了 的细菌细胞分裂。这些化合物可能成为新型抗 药物的起点，这里提出的策略提出了一种绕过细菌未来任何耐药性的机制。
