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Antisense inhibition of accA in E. coli suppressed luxS expression and increased antibiotic susceptibility
bioRxiv - Synthetic Biology Pub Date : 2020-11-01 , DOI: 10.1101/747980
Tatiana Hillman

Bacterial multiple drug resistance is a significant issue for the medical community. Gram-negative bacteria exhibit higher rates of multi-drug resistance, partly due to the impermeability of the Gram-negative bacterial cell wall and double-membrane cell envelope, which limits the internal accumulation of antibiotic agents. The outer lipopolysaccharide membrane regulates the transport of hydrophobic molecules, while the inner phospholipid membrane controls influx of hydrophilic particles. In Escherichia coli, the gene accA produces the acetyl-CoA carboxylase transferase enzyme required for catalyzing synthesis of fatty acids and phospholipids that compose the inner membrane. To increase antibiotic susceptibility and decrease growth, this study interrupted fatty acid synthesis and disrupted the composition of the inner membrane through inhibiting the gene accA with antisense RNA. This inhibition suppressed expression of luxS, a vital virulence factor that regulates cell growth, transfers intercellular quorum-sensing signals mediated by autoinducer-2, and is necessary for biofilm formation. Bacterial cells in which accA was inhibited also displayed a greater magnitude of antibiotic susceptibility. These findings confirm accA as a potent target for developing novel antibiotics such as antimicrobial gene therapies.

中文翻译:

在大肠杆菌中反义抑制accA可抑制luxS表达并增加抗生素敏感性

细菌多重耐药性是医学​​界的重要问题。革兰氏阴性细菌表现出较高的多重耐药性,部分原因是革兰氏阴性细菌细胞壁和双膜细胞包膜的不渗透性限制了抗生素药物的内部积累。外部脂多糖膜调节疏水分子的运输,而内部磷脂膜控制亲水性颗粒的流入。在大肠杆菌中,基因accA产生乙酰辅酶A羧化酶转移酶,该酶催化组成内膜的脂肪酸和磷脂的合成。为了增加抗生素敏感性并减少生长,这项研究通过反义RNA抑制accA基因,中断了脂肪酸的合成并破坏了内膜的组成。这种抑制作用抑制了luxS的表达,luxS是调节细胞生长,转移由autoinducer-2介导的细胞间群体感应信号的重要毒力因子,对于生物膜的形成是必需的。accA被抑制的细菌细胞也表现出更大的抗生素敏感性。这些发现证实accA是开发新型抗生素(例如抗菌基因疗法)的有效靶标。accA被抑制的细菌细胞也表现出更大的抗生素敏感性。这些发现证实accA是开发新型抗生素(例如抗菌基因疗法)的有效靶标。accA被抑制的细菌细胞也表现出更大的抗生素敏感性。这些发现证实accA是开发新型抗生素(例如抗菌基因疗法)的有效靶标。
更新日期:2020-11-02
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