Ayllon Marcelo, Abatchev Gamid, Bogard Andrew, Whiting Rosey, Hobdey Sarah E, Fologea Daniel
Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725, USA.
Department of Physics, Boise State University, Boise, ID 83725, USA.
Membranes (Basel). 2021 May 18;11(5):364. doi: 10.3390/membranes11050364.
The need for alternatives to antibiotics in the fight against infectious diseases has inspired scientists to focus on antivirulence factors instead of the microorganisms themselves. In this respect, prior work indicates that tiny, enclosed bilayer lipid membranes (liposomes) have the potential to compete with cellular targets for toxin binding, hence preventing their biological attack and aiding with their clearance. The effectiveness of liposomes as decoy targets depends on their availability in the host and how rapidly they are cleared from the circulation. Although liposome PEGylation may improve their circulation time, little is known about how such a modification influences their interactions with antivirulence factors. To fill this gap in knowledge, we investigated regular and long-circulating liposomes for their ability to prevent in vitro red blood cell hemolysis induced by two potent lytic toxins, lysenin and streptolysin O. Our explorations indicate that both regular and long-circulating liposomes are capable of similarly preventing lysis induced by streptolysin O. In contrast, PEGylation reduced the effectiveness against lysenin-induced hemolysis and altered binding dynamics. These results suggest that toxin removal by long-circulating liposomes is feasible, yet dependent on the particular virulence factor under scrutiny.
在对抗传染病的过程中，对抗生素替代品的需求促使科学家们将重点放在抗毒力因子而非微生物本身。在这方面，先前的研究表明，微小的封闭双层脂质膜（脂质体）有可能与细胞靶点竞争毒素结合，从而防止毒素的生物攻击并促进其清除。脂质体作为诱饵靶点的有效性取决于它们在宿主体内的可用性以及从循环中清除的速度。尽管脂质体聚乙二醇化可能会延长其循环时间，但对于这种修饰如何影响它们与抗毒力因子的相互作用却知之甚少。为了填补这一知识空白，我们研究了常规脂质体和长循环脂质体预防两种强效溶解毒素（溶细胞素和链球菌溶血素O）诱导的体外红细胞溶血的能力。我们的研究表明，常规脂质体和长循环脂质体都能够同样有效地预防链球菌溶血素O诱导的细胞溶解。相比之下，聚乙二醇化降低了对溶细胞素诱导的溶血的预防效果，并改变了结合动力学。这些结果表明，长循环脂质体去除毒素是可行的，但取决于所研究的特定毒力因子。
