Abstract
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.
Highlights
Secreted pore-forming toxins (PFTs) are a distinct class of molecules that disrupt the barrier function through introducing large, unregulated pores in the host cell membranes [1,2,3,4,5,6]
The detailed compositions and physical characterization of liposomes prepared by sonication or extrusion and utilized in this work are presented in Table 1; liposome characterization by DLS provided the average diameter and polydispersity index (PDI)
We focused our investigations on exploring the ability of regular and longcirculating liposomes produced by either sonication or extrusion to prevent hemolysis of red blood cell (RBC) exposed to lysenin
Summary
Secreted pore-forming toxins (PFTs) are a distinct class of molecules that disrupt the barrier function through introducing large, unregulated pores in the host cell membranes [1,2,3,4,5,6]. Prior in vivo experiments showed that long-circulating, SM-rich liposomes had a half-maximal decline at 4 h owing to elimination by splenic macrophages, which may lead to the requirement of multiple treatments with liposomes at short time intervals [28] This may limit the applicability of liposomes to effectively remove only toxins for which SM is a preferred target. As PEG addition is intended to minimize undesired interactions, we asked whether or not such liposomes are efficient targets for toxins, actively contributing to their clearance To answer this question, we investigated the ability of PEGylated liposomes (long-circulating liposomes) to prevent RBC lysis elicited by two potent poreforming toxins, SLO [44,45] and lysenin [46,47,48]. The analysis of the inhibition plots revealed that the toxin binding to target membranes is a cooperative process influenced by the toxin’s identity and lipid composition of the liposomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
