Pyruvate-depleting conditions induce biofilm dispersion and enhance the efficacy of antibiotics in killing biofilms in vitro and in vivo
Pyruvate-depleting conditions induce biofilm dispersion and enhance the efficacy of antibiotics in killing biofilms in vitro and in vivo
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DOI：
10.1038/s41598-019-40378-z
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发表时间：
2019-03-06
影响因子：
4.6
通讯作者：
Sauer, Karin
中科院分区：
文献类型：
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作者：
Goodwine, James;Gil, Joel;Sauer, Karin
生物膜的形成是一个发育过程，它是由过渡到表面的无张力细胞启动的，当细胞从生物膜中分散并过渡到无张力生长模式时，它就完成了一个完整的循环。考虑到丙酮酸盐先前已被证明是铜绿假单胞菌生物膜形成所需的，我们询问丙酮酸盐是否同样有助于维持生物膜结构，其中丙酮酸盐的消耗导致分散。在这里，我们证明了丙酮酸的酶消耗与S.金黄色葡萄球菌和实验室和临床铜绿假单胞菌分离株。分散反应依赖于丙酮酸发酵途径组分，但独立于先前描述的有助于铜绿假单胞菌生物膜分散的蛋白质。使用感染铜绿假单胞菌生物膜细胞的猪二度烧伤伤口，我们进一步证明丙酮酸消耗导致体内生物膜生物量减少。丙酮酸消耗条件增强妥布霉素杀死驻留伤口生物膜的功效达5个对数。我们的研究结果强烈表明，丙酮酸可用性的管理是一个很有前途的战略，以打击生物膜相关的感染与伤口和囊性纤维化肺部感染的两个主要病原体。
The formation of biofilms is a developmental process initiated by planktonic cells transitioning to the surface, which comes full circle when cells disperse from the biofilm and transition to the planktonic mode of growth. Considering that pyruvate has been previously demonstrated to be required for the formation of P. aeruginosa biofilms, we asked whether pyruvate likewise contributes to the maintenance of the biofilm structure, with depletion of pyruvate resulting in dispersion. Here, we demonstrate that the enzymatic depletion of pyruvate coincided with the dispersion of established biofilms by S. aureus and laboratory and clinical P. aeruginosa isolates. The dispersion response was dependent on pyruvate fermentation pathway components but independent of proteins previously described to contribute to P. aeruginosa biofilm dispersion. Using porcine second-degree burn wounds infected with P. aeruginosa biofilm cells, we furthermore demonstrated that pyruvate depletion resulted in a reduction of biofilm biomass in vivo. Pyruvate-depleting conditions enhanced the efficacy of tobramycin killing of the resident wound biofilms by up to 5-logs. Our findings strongly suggest the management of pyruvate availability to be a promising strategy to combat biofilm-related infections by two principal pathogens associated with wound and cystic fibrosis lung infections.