Department of Critical Care Medicine, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, 570208, China.
College of Environment and Resources, Xiangtan University, Xiangtan, 411105, China.
Appl Microbiol Biotechnol. 2019 Aug;103(15):6195-6204. doi: 10.1007/s00253-019-09905-w. Epub 2019 May 25.
Pseudomonas aeruginosa biofilm lifestyle exhibits multidrug resistance in chronic bacterial infections. Alternative antimicrobial compounds or combination drug therapies must be urgently developed. In this work, the antibiofilm effect of Ag nanoparticle (AgNP) combined with the quorum sensing inhibitor (QSI) 4-nitropyridine N-oxide (4NPO) on P. aeruginosa biofilms was investigated. The biofilm biomass of P. aeruginosa was considerably reduced by 1.56-50 mg/L AgNP. However, 4NPO enhanced the ability of AgNP to inhibit P. aeruginosa biofilm formation (P < 0.05). The combination of AgNP with 4NPO could continuously inhibit biofilm development after 12 h, and 50 mg/L AgNP combined with 6.25 mg/L 4NPO thoroughly suppressed biofilm growth. The expression levels of QS genes and exopolysaccharide genes of biofilm treated with the combination of AgNP with 4NPO (AgNP-4NPO combination) were lower than those treated with AgNP alone (P < 0.05). Additional extracellular proteins and polysaccharides were determined in the samples treated with AgNP-4NPO combination. Based on proteomic analysis, this result was attributed to cell rupture caused by antimicrobial agents and intracellular materials released. The combination of the two antimicrobial agents could weaken the swimming ability of bacterial cells by damaging bacterial flagella and blocking rhlA gene expression. Thus, AgNP combined with QSI showed stronger antibiofilm ability than AgNP alone. These results may contribute to the development of antimicrobial agents.
铜绿假单胞菌生物膜生活方式表现出慢性细菌感染的多药耐药性。必须紧急开发替代抗菌化合物或联合药物疗法。在这项工作中，研究了银纳米颗粒 (AgNP) 与群体感应抑制剂 (QSI) 4-硝基吡啶 N-氧化物 (4NPO) 联合对铜绿假单胞菌生物膜的抗生物膜作用。AgNP 的浓度为 1.56-50 mg/L 时，铜绿假单胞菌生物膜的生物量显著减少。然而，4NPO 增强了 AgNP 抑制铜绿假单胞菌生物膜形成的能力 (P < 0.05)。AgNP 与 4NPO 联合使用可在 12 h 后持续抑制生物膜的发展，并且 50 mg/L AgNP 与 6.25 mg/L 4NPO 联合可彻底抑制生物膜的生长。用 AgNP 与 4NPO 的组合处理的生物膜的 QS 基因和胞外多糖基因的表达水平低于单独用 AgNP 处理的生物膜 (P < 0.05)。在用 AgNP-4NPO 组合处理的样品中还确定了额外的细胞外蛋白质和多糖。基于蛋白质组学分析，这一结果归因于抗菌剂引起的细胞破裂和细胞内物质的释放。两种抗菌剂的组合通过破坏细菌鞭毛和阻断 rhlA 基因表达来削弱细菌细胞的泳动能力。因此，AgNP 与 QSI 的联合使用比单独使用 AgNP 具有更强的抗生物膜能力。这些结果可能有助于开发抗菌剂。
