Tailored liposomal nanotraps for the treatment of Streptococcal infections

Abstract Background Streptococcal 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 provide...

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Main Authors: Hervé Besançon, Viktoriia Babiychuk, Yu Larpin, René Köffel, Dominik Schittny, Lara Brockhus, Lucy J. Hathaway, Parham Sendi, Annette Draeger, Eduard Babiychuk
Format: Article
Language:English
Published: BMC 2021-02-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-021-00775-x
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author Hervé Besançon
Viktoriia Babiychuk
Yu Larpin
René Köffel
Dominik Schittny
Lara Brockhus
Lucy J. Hathaway
Parham Sendi
Annette Draeger
Eduard Babiychuk
author_facet Hervé Besançon
Viktoriia Babiychuk
Yu Larpin
René Köffel
Dominik Schittny
Lara Brockhus
Lucy J. Hathaway
Parham Sendi
Annette Draeger
Eduard Babiychuk
author_sort Hervé Besançon
collection DOAJ
description Abstract Background Streptococcal 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. Results In 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. Conclusions Unravelling 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.
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spelling doaj.art-ef137a52471f4d6bbf852b1b4d4f936b2022-12-22T04:20:50ZengBMCJournal of Nanobiotechnology1477-31552021-02-0119111510.1186/s12951-021-00775-xTailored liposomal nanotraps for the treatment of Streptococcal infectionsHervé Besançon0Viktoriia Babiychuk1Yu Larpin2René Köffel3Dominik Schittny4Lara Brockhus5Lucy J. Hathaway6Parham Sendi7Annette Draeger8Eduard Babiychuk9Institute of Anatomy, University of BernInstitute of Anatomy, University of BernInstitute of Anatomy, University of BernInstitute of Anatomy, University of BernInstitute of Anatomy, University of BernInstitute of Anatomy, University of BernInstitute for Infectious Diseases, University of BernInstitute for Infectious Diseases, University of BernInstitute of Anatomy, University of BernInstitute of Anatomy, University of BernAbstract Background Streptococcal 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. Results In 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. Conclusions Unravelling 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.https://doi.org/10.1186/s12951-021-00775-xInfectionStreptococcusToxinLiposomeNanotrap
spellingShingle Hervé Besançon
Viktoriia Babiychuk
Yu Larpin
René Köffel
Dominik Schittny
Lara Brockhus
Lucy J. Hathaway
Parham Sendi
Annette Draeger
Eduard Babiychuk
Tailored liposomal nanotraps for the treatment of Streptococcal infections
Journal of Nanobiotechnology
Infection
Streptococcus
Toxin
Liposome
Nanotrap
title Tailored liposomal nanotraps for the treatment of Streptococcal infections
title_full Tailored liposomal nanotraps for the treatment of Streptococcal infections
title_fullStr Tailored liposomal nanotraps for the treatment of Streptococcal infections
title_full_unstemmed Tailored liposomal nanotraps for the treatment of Streptococcal infections
title_short Tailored liposomal nanotraps for the treatment of Streptococcal infections
title_sort tailored liposomal nanotraps for the treatment of streptococcal infections
topic Infection
Streptococcus
Toxin
Liposome
Nanotrap
url https://doi.org/10.1186/s12951-021-00775-x
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