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Effect of itraconazole on Staphylococcus aureus biofilm and extracellular vesicles formation.
Microbial Pathogenesis ( IF 3.8 ) Pub Date : 2020-05-25 , DOI: 10.1016/j.micpath.2020.104267
S Frassinetti 1 , A Falleni 2 , R Del Carratore 3
Affiliation  

Staphylococcus aureus is a leading cause of a wide range of clinical chronic infections mainly due to the establishment of a biofilm. Biofilm, a population of bacteria within a self-produced matrix of extracellular polymeric substance, decreases the susceptibility to antibiotics, immune defenses and contributes to antimicrobial resistance. To date antibiotic combination has been considered a strategy to combat S. aureus infection, but this approach does not solves the main pharmacokinetic problem caused by biofilms, consisting in insufficient drug penetration within the structure. Therefore, new antimicrobial agents that could overcome this resistance need to be discovered. Fighting staphylococcal resistance and biofilm formation is an important goal of the pharmaceutical research. Some fungicide has been observed to have antibacterial effect anyway their use as antibiotics on S.aureus has been poorly studied. The aim of this work was to investigate the effect of the fungicide itraconazole (IT) on S. aureus biofilm formation and explore by SEM the morphological alteration after treatment. A strong biofilm disaggregation and morphologically different extracellular vesicles (EV) production were observed starting from sublethal IT doses. This suggests that IT resistance phenomena on the part of S. aureus are more difficult to establish respect other antibiotics. The adjuvant properties of IT could be used to combat bacterial biofilm and/or to improve antibiotic treatment. Moreover because the production of EV represents a secretory pathway involved in intercellular communication shared to mammalian cells, fungi, and bacteria, our study is important to increase information that can be generalized to higher organisms.



中文翻译:

伊曲康唑对金黄色葡萄球菌生物膜和细胞外囊泡形成的影响。

金黄色葡萄球菌是引起广泛的临床慢性感染的主要原因,这主要是由于生物膜的建立。生物膜是在细胞外聚合物质的自我产生的基质内的细菌种群,可降低对抗生素的敏感性,免疫防御能力,并有助于产生抗药性。迄今为止,抗生素组合被认为是对抗金黄色葡萄球菌的一种策略感染,但这种方法不能解决由生物膜引起的主要药代动力学问题,该问题包括结构内药物渗透不足。因此,需要发现可以克服这种耐药性的新型抗菌剂。对抗葡萄球菌耐药性和生物膜形成是药物研究的重要目标。不管怎样,已经观察到一些杀真菌剂具有抗菌作用,反而对它们用作金黄色葡萄球菌的抗生素的研究很少。这项工作的目的是调查杀菌剂伊曲康唑(IT)对金黄色葡萄球菌的影响生物膜形成,并通过SEM观察处理后的形态变化。从亚致死剂量开始,观察到强烈的生物膜分解和形态学上不同的细胞外囊泡(EV)产生。这表明金黄色葡萄球菌对IT的抗药性现象较其他抗生素难以建立。IT的佐剂特性可用于对抗细菌生物膜和/或改善抗生素治疗。而且,由于EV的产生代表了与哺乳动物细胞,真菌和细菌共享的细胞间通讯所涉及的分泌途径,因此我们的研究对于增加可推广至高等生物的信息非常重要。

更新日期:2020-05-25
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