加州大学圣地亚哥分校 亚麻籽中的亚麻酸可以杀死幽门螺旋杆菌

Mechanism of Antibacterial Activity of Liposomal Linolenic Acid against Helicobacter pylori

 

 

图示:Ulcer-causing Bacterium (H.Pylori) Crossing Mucus Layer of Stomach, using flagella  利用鞭毛穿过胃粘膜,形成溃疡的细菌(H.Pylori)

 

幽门螺杆菌感染约占世界人口的一半,是引起胃炎、消化性溃疡和胃癌的主要原因。此外,这种细菌对所有主要的抗生素都有抗药性。

 

 

最近,我们开发了一种新型脂质体亚麻酸(LipoLLA)制剂,对几种临床分离的幽门螺杆菌耐药菌株(包括螺旋型和球菌型)具有很强的杀菌活性。

 

 

 

此外,LipoLLA在体内治疗效果优于标准的三联疗法。我们的数据显示LipoLLA与幽门螺杆菌细胞膜有关。

 

 

 

因此,在本研究中,我们研究了LipoLLA对幽门螺旋杆菌可能的抗菌机制。

 

与脂质体硬脂酸(LipoSA, C18:0)和油酸(LipoOA, C18:1)相比,LipoLLA (C18:3)的抗菌活性。LipoLLA杀菌效果最强,在5分钟内完全杀死了幽门螺杆菌。

 

 

 

 

LipoOALipoLLA处理后,幽门螺杆菌外膜的通透性增加。此外,通过检测细菌释放的三磷酸腺苷(ATP),我们发现LipoLLA处理的幽门螺杆菌的菌质膜比LipoOA处理的菌质膜具有明显更高的通透性,导致细菌细胞死亡。

 

 

 

通过透射电镜(TEM)和扫描电镜(SEM)观察,LipoLLA5min内造成了细菌膜的结构变化,影响了膜的完整性,导致细胞质内容物渗漏。

 

 

 

 

我们的发现表明LipoLLA具有快速杀菌作用,这表明它是一种很有前途的新型有效的抗幽门螺旋杆菌药物。

 

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116519

Mechanism of Antibacterial Activity of Liposomal Linolenic Acid against Helicobacter pylori

 

Helicobacter pylori infects approximately half of the world population and is a major cause of gastritis, peptic ulcer, and gastric cancer. Moreover, this bacterium has quickly developed resistance to all major antibiotics.

 

Recently, we developed a novel liposomal linolenic acid (LipoLLA) formulation, which showed potent bactericidal activity against several clinical isolated antibiotic-resistant strains of H. pylori including both the spiral and coccoid form.

 

In addition, LipoLLA had superior in vivo efficacy compared to the standard triple therapy.

 

Our data showed that LipoLLA associated with H. pylori cell membrane.

 

Therefore, in this study, we investigated the possible antibacterial mechanism of LipoLLA against H. pylori. The antibacterial activity of LipoLLA (C18:3) was compared to that of liposomal stearic acid (LipoSA, C18:0) and oleic acid (LipoOA, C18:1).

 

LipoLLA showed the most potent bactericidal effect and completely killed H. pylori within 5 min. The permeability of the outer membrane of H. pylori increased when treated with LipoOA and LipoLLA.

 

Moreover, by detecting released adenosine triphosphate (ATP) from bacteria, we found that bacterial plasma membrane of H. pylori treated with LipoLLA exhibited significantly higher permeability than those treated with LipoOA, resulting in bacteria cell death.

 

Furthermore, LipoLLA caused structural changes in the bacterial membrane within 5 min affecting membrane integrity and leading to leakage of cytoplasmic contents, observed by both transmission electron microscopy (TEM) and scanning electron microscopy (SEM).

 

 

Our findings showing rapid bactericidal effect of LipoLLA suggest it is a very promising new, effective anti-H. pylori agent.

 

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116519