Engineered Liposomes Protect Immortalized Immune Cells from Cytolysins Secreted by Group A and Group G Streptococci

Abstract

The increasing antibiotic resistance of bacterial pathogens fosters the development of alternative, non-antibiotic treatments. Antivirulence therapy, which is neither bacteriostatic nor bactericidal, acts by depriving bacterial pathogens of their virulence factors. To establish a successful infection, many bacterial pathogens secrete exotoxins/cytolysins that perforate the host cell plasma membrane. Recently developed liposomal nanotraps, mimicking the outer layer of the targeted cell membranes, serve as decoys for exotoxins, thus diverting them from attacking host cells. In this study, we develop a liposomal nanotrap formulation that is capable of protecting immortalized immune cells from the whole palette of cytolysins secreted by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis—important human pathogens that can cause life-threatening bacteremia. We show that the mixture of cholesterol-containing liposomes with liposomes composed exclusively of phospholipids is protective against the combined action of all streptococcal exotoxins. Our findings pave the way for further development of liposomal antivirulence therapy in order to provide more efficient treatment of bacterial infections, including those caused by antibiotic resistant pathogens.

Bacterial pore-forming toxin pneumolysin drives pathogenicity through shed toxin-loaded host extracellular vesicles

“…Further, we also showed that the shed EVs harbour membrane-localized PLY, which is in agreement with previous studies that showed the expulsion of PLY pores from cells though microvesicle shedding ( 12, 14, 37 ). However, the downstream effects of the shed PLY-EVs on the host are unknown and it is believed that the pore-forming toxins are completely neutralized upon capture by synthetic cholesterol-containing liposomes ( 38-40 ). However, neither of these studies investigated the downstream effects of the toxin-soaked liposomes.…”