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.
Highlights
Antibiotic resistance, in combination with a longer living and increasingly immunocompromised population, is a global health threat
We examined whether GAS and GGS strains possessed cytolytic and/or cytotoxic activities towards the following nucleated immune cells: THP-1, Jurkat (T lymphoid cell line), and Raji (B lymphoid cell line)
All immune cells died when challenged with bacterial supernatants, indicating that all GAS and GGS strains that were used in this study possess potent cytolytic/cytotoxic activities (Figure 1)
Summary
Antibiotic resistance, in combination with a longer living and increasingly immunocompromised population, is a global health threat. Whereas pathogens continue to adapt and evade the currently available therapies, new antibiotics are lacking in the pharmaceutical pipelines, as they are difficult and expensive to develop and commercialize [1]. Common guidelines to fight antibiotic resistance focus on the development of alternative treatments [2]. One promising approach is antivirulence therapy, which inhibits virulence factors—molecules that are produced by pathogens in order to establish a persistent infection [3]. Antivirulence drugs strip the pathogen of its virulence properties but do not directly kill it, thereby reducing selective pressure to develop resistance mechanisms [4]. Antivirulence drugs promote bacterial clearance by the immune system and can be used as joined therapeutic agents with antibiotics
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