Infections associated with antimicrobial-resistant bacteria now represent a significant threat to human health using conventional therapy, necessitating the development of alternate and more effective antibacterial compounds. Silver nanoparticles (Ag NPs) have been proposed as potential antimicrobial agents to combat infections. A complete understanding of their antimicrobial activity is required before these molecules can be used in therapy. Lysozyme coated Ag NPs were synthesized and characterized by TEM-EDS, XRD, UV-vis, FTIR spectroscopy, zeta potential and oxidative potential assay. Biochemical assays and deep level transcriptional analysis using RNA sequencing were used to decipher how Ag NPs exert their antibacterial action against multi-drug resistant Klebsiella pneumoniae MGH78578. RNAseq data revealed that Ag NPs induced a triclosan-like bactericidal mechanism responsible for the inhibition of the type II fatty acid biosynthesis. Additionally, released Ag+ generated oxidative stress both extra- and intracellularly in K. pneumoniae. The data showed that triclosan-like activity and oxidative stress cumulatively underpinned the antibacterial activity of Ag NPs. This result was confirmed by the analysis of the bactericidal effect of Ag NPs against the isogenic K. pneumoniae MGH78578 ΔsoxS mutant, which exhibits a compromised oxidative stress response compared to the wild type. Silver nanoparticles induce a triclosan-like antibacterial action mechanism in multi-drug resistant K. pneumoniae. This study extends our understanding of anti-Klebsiella mechanisms associated with exposure to Ag NPs. This allowed us to model how bacteria might develop resistance against silver nanoparticles, should the latter be used in therapy.

中文翻译：

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银纳米颗粒在耐多药肺炎克雷伯菌中诱导三氯生样抗菌作用机制

目的：使用常规疗法，与抗药性细菌相关的感染现在对人类健康构成重大威胁，因此有必要开发其他更有效的抗菌化合物。银纳米颗粒（Ag NPs）已被提议作为对抗感染的潜在抗菌剂。在将这些分子用于治疗之前，需要全面了解其抗菌活性。方法：通过TEM-EDS，XRD，UV-vis，FTIR，zeta电势和氧化电势的测定，合成了溶菌酶包被的Ag纳米颗粒。生化分析和使用RNA测序的深层转录分析被用来解释Ag NPs如何发挥其对多重耐药肺炎克雷伯菌肺炎MGH78578的抗菌作用。结果：RNAseq数据显示，Ag NPs诱导了一种三氯生样杀菌机制，该机制可抑制II型脂肪酸的生物合成。另外，释放的Ag +在肺炎克雷伯菌中在细胞外和细胞内均产生氧化应激。数据表明，三氯生样活性和氧化应激累积增强了Ag NPs的抗菌活性。通过分析Ag NPs对等基因肺炎克雷伯氏菌MGH78578ΔsoxS突变体的杀菌作用，证实了该结果，与野生型相比，该突变体表现出受损的氧化应激反应。结论：银纳米颗粒对耐多药肺炎克雷伯菌具有三氯生类抗菌作用。这项研究扩展了我们对与暴露于银纳米颗粒相关的抗克雷伯菌的机制的理解。