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首页> 外文期刊>Antimicrobial agents and chemotherapy. >An Antipersister Strategy for Treatment of Chronic Pseudomonas aeruginosa Infections
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An Antipersister Strategy for Treatment of Chronic Pseudomonas aeruginosa Infections

机译：治疗慢性假单胞菌铜绿假单胞菌感染的止回战略

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摘要

Bacterial persisters are a quasidormant subpopulation of cells that are tolerant to antibiotic treatment. The combination of the aminoglycoside tobramycin with fumarate as an antibacterial potentiator utilizes an antipersister strategy that is aimed at reducing recurrent Pseudomonas aeruginosa infections by enhancing the killing of P. aeruginosa persisters. Stationary-phase cultures of P. aeruginosa were used to generate persister cells. A range of tobramycin concentrations was tested with a range of metabolite concentrations to determine the potentiation effect of the metabolite under a variety of conditions, including a range of pH values and in the presence of azithromycin or cystic fibrosis (CF) patient sputum. In addition, 96-well dish biofilm and colony biofilm assays were performed, and the cytotoxicity of the tobramycin-fumarate combination was determined utilizing a lactate dehydrogenase (LDH) assay. Enhanced killing of up to 6 orders of magnitude of P. aeruginosa persisters over a range of CF isolates, including mucoid and nonmucoid strains, was observed for the tobramycin-fumarate combination compared to killing with tobramycin alone. Furthermore, significant fumarate-mediated potentiation was seen in the presence of azithromycin or CF patient sputum. Fumarate also reduced the cytotoxicity of tobramycin-treated P. aeruginosa to human epithelial airway cells. Finally, in mucoid and nonmucoid CF isolates, complete eradication of P. aeruginosa biofilm was observed in the colony biofilm assay due to fumarate potentiation. These data suggest that a combination of tobramycin with fumarate as an antibacterial potentiator may be an attractive therapeutic for eliminating recurrent P. aeruginosa infections in CF patients through the eradication of bacterial persisters.
机译：细菌持久性是一种拟常规的细胞亚群，其耐受抗生素治疗。氨基糖苷类毒素与富马酸盐作为抗菌强剂的组合利用止回体策略，旨在通过增强抗铜绿假单胞菌持续体的杀伤来减少复发性假单胞菌铜绿假单胞菌感染。铜绿假单胞菌的固定相培养物用于产生抗静电细胞。通过一系列代谢物浓度测试一系列毒素浓度，以确定代谢物在各种条件下的增强效果，包括一系列pH值和在氮霉素存在或囊性纤维化（CF）患者痰液中。另外，进行96孔盘生物膜和菌落生物膜测定，利用乳酸脱氢酶（LDH）测定测定卷霉素 - 富马酸盐组合的细胞毒性。与单独的染发蛋白杀死相比，观察到在一系列CF分离株（包括粘膜 - 富马酸盐）组合的CF分离物中，增强了高达6次P.Meruginosa持续存在的损伤。此外，在阿奇霉素或CF患者痰液存在下观察到显着的富马酸型介导的增强。富马酸盐还将对人上皮气道细胞的烟草处理的P.铜绿假单胞菌的细胞毒性降低。最后，在粘液和非饼CF分离物中，由于富马酸富含量的增强，在菌落生物膜测定中，在菌落生物膜测定中完全消除了P.铜绿假膜生物膜。这些数据表明，用富马酸盐作为抗菌剂引发剂的烟霉素组合可以是消除CF患者的复发性P.铜绿假单胞菌感染通过消除细菌持久性的含有吸引力的治疗方法。

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