Abstract
BackgroundStreptococcal infections are associated with life-threatening pneumonia and sepsis. The rise in antibiotic resistance calls for novel approaches to treat bacterial diseases. Anti-virulence strategies promote a natural way of pathogen clearance by eliminating the advantage provided to bacteria by their virulence factors. In contrast to antibiotics, anti-virulence agents are less likely to exert selective evolutionary pressure, which is a prerequisite for the development of drug resistance. As part of their virulence mechanism, many bacterial pathogens secrete cytolytic exotoxins (hemolysins) that destroy the host cell by destabilizing their plasma membrane. Liposomal nanotraps, mimicking plasmalemmal structures of host cells that are specifically targeted by bacterial toxins are being developed in order to neutralize-by competitive sequestration-numerous exotoxins.ResultsIn this study, the liposomal nanotrap technology is further developed to simultaneously neutralize the whole palette of cytolysins produced by Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis-pathogens that can cause life-threatening streptococcal toxic shock syndrome. We show that the mixture of liposomes containing high amounts of cholesterol and liposomes composed exclusively of choline-containing phospholipids is fully protective against the combined action of exotoxins secreted by these pathogens.ConclusionsUnravelling the universal mechanisms that define targeting of host cells by streptococcal cytolysins paves the way for a broad-spectrum anti-toxin therapy that can be applied without a diagnostic delay for the treatment of bacterial infections including those caused by antibiotic-resistant pathogens.
Highlights
Infectious diseases are responsible for a staggering 15 million deaths annually, accounting for more than half of the deaths in low income countries [1, 2]
We have shown that the whole toxin secretomes of S. pneumoniae and S. aureus contain additional cytotoxic activities that are different from hemolytic activities of PLY and α-hemolysin and that require nanotraps composed exclusively of sphingomyelin for their neutralization
All strains of S. pneumoniae, GAS and GGS used in this study possessed potent hemolytic activities that were comparable between species (Fig. 1a, b)
Summary
Infectious diseases are responsible for a staggering 15 million deaths annually, accounting for more than half of the deaths in low income countries [1, 2]. Virulence factors are specific agents produced by bacterial pathogens that allow them to survive within the hostile environment of the targeted organism [2, 4, Besançon et al J Nanobiotechnol (2021) 19:46. An anti-virulence treatment eliminates the advantage provided by targeted virulence factors, promoting bacterial clearance by the immune system. Anti-virulence strategies promote a natural way of pathogen clearance by eliminating the advantage provided to bacteria by their virulence factors. Anti-virulence agents are less likely to exert selective evolutionary pressure, which is a prerequisite for the development of drug resistance. As part of their virulence mechanism, many bacterial pathogens secrete cytolytic exotoxins (hemolysins) that destroy the host cell by destabilizing their plasma membrane. Liposomal nanotraps, mimicking plasmalemmal structures of host cells that are targeted by bacterial toxins are being developed in order to neutralize-by competitive sequestration-numerous exotoxins
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