Gold nanocluster adjuvant enables the eradication of persister cells by antibiotics and abolishes the emergence of resistance.
Gold nanocluster adjuvant enables the eradication of persister cells by antibiotics and abolishes the emergence of resistance.
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持续性细胞是囊性纤维化和慢性化脓性中耳炎（CSOM）中常见感染复发的原因。然而，目前还没有食品和药物管理局（FDA）批准的抗生素来根除持久性细胞。令人沮丧的是，全球临床前细菌管道不包含针对持久性细胞的抗菌剂。因此，我们报道了一种基于金纳米簇佐剂的非传统抗菌化疗策略，以根除属于不同类别的现有抗生素的持久性细胞。与单独使用抗生素相比，抗生素和AuNC@CPP联合使用可以使持久性细胞和生物膜绝育。在铜绿假单胞菌感染的CSOM小鼠模型中，当抗生素和AuNC@CPP联合使用时，观察到高达4个数量级的增强杀伤，为改善CSOM的治疗提供了潜在的方法。我们确定AuNC@CPP的作用机制是由于质子梯度和膜超极化的破坏。这里提出的方法可以弥补缺乏新的抗生素来对抗持久性细胞。这种方法也有利于目前减缓耐药性发展的努力，因为AuNC@CPP消除了抗生素诱导的耐药菌株的出现。
Persister cells are responsible for relapses of infections common in cystic fibrosis and chronic suppurative otitis media (CSOM). Yet, there are no Food and Drug Administration (FDA) approved antibiotics to eradicate persister cells. Frustratingly, the global preclinical bacterial pipeline does not contain antibacterial agents targeting persister cells. Therefore, we report a nontraditional antimicrobial chemotherapy strategy based on gold nanoclusters adjuvant to eradicate persister cells by existing antibiotics belonging to that different class. Compared to killing with antibiotics alone, combining antibiotics and AuNC@CPP sterilizes persister cells and biofilms. Enhanced killing of up to 4 orders of magnitude in a validated mouse model of CSOM with Pseudomonas aeruginosa infection was observed when combining antibiotics and AuNC@CPP, informing a potential approach to improve the treatment of CSOM. We established that the mechanism of action of AuNC@CPP is due to disruption of the proton gradient and membrane hyperpolarization. The method presented here could compensate for the lack of new antibiotics to combat persister cells. This method could also benefit the current effort to slow resistance development because AuNC@CPP abolished the emergence of drug-resistant strains induced by antibiotics.
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影响因子：
3.6
作者：
Bhaumik KN;Hetényi A;Olajos G;Martins A;Spohn R;Németh L;Jojart B;Szili P;Dunai A;Jangir PK;Daruka L;Földesi I;Kata D;Pál C;Martinek TA
通讯作者：
Martinek TA
影响因子：
5.3
作者：
Fu X;Wan P;Li P;Wang J;Guo S;Zhang Y;An Y;Ye C;Liu Z;Gao J;Yang J;Fan J;Chai R
通讯作者：
Chai R
影响因子：
--
作者：
Farha, Maya A.;Verschoor, Chris P.;Brown, Eric D.
通讯作者：
Brown, Eric D.
影响因子：
56.9
作者：
Keren, Iris;Wu, Yanxia;Lewis, Kim
通讯作者：
Lewis, Kim
影响因子：
4.9
作者：
Koeva, Martina;Gutu, Alina D.;Joseph-McCarthy, Diane
通讯作者：
Joseph-McCarthy, Diane