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Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium

The prevalence of bacterial pathogens being resistant to antibiotic treatment is increasing worldwide, leading to a severe global health challenge. Simultaneously, the development and approval of new antibiotics stagnated in the past decades, leading to an urgent need for novel approaches to avoid t...

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Detalles Bibliográficos
Autores principales: von Ambüren, Julia, Schreiber, Fynn, Fischer, Julia, Winter, Sandra, van Gumpel, Edeltraud, Simonis, Alexander, Rybniker, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463580/
https://www.ncbi.nlm.nih.gov/pubmed/32707871
http://dx.doi.org/10.3390/microorganisms8081096
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author von Ambüren, Julia
Schreiber, Fynn
Fischer, Julia
Winter, Sandra
van Gumpel, Edeltraud
Simonis, Alexander
Rybniker, Jan
author_facet von Ambüren, Julia
Schreiber, Fynn
Fischer, Julia
Winter, Sandra
van Gumpel, Edeltraud
Simonis, Alexander
Rybniker, Jan
author_sort von Ambüren, Julia
collection PubMed
description The prevalence of bacterial pathogens being resistant to antibiotic treatment is increasing worldwide, leading to a severe global health challenge. Simultaneously, the development and approval of new antibiotics stagnated in the past decades, leading to an urgent need for novel approaches to avoid the spread of untreatable bacterial infections in the future. We developed a highly comprehensive screening platform based on quantification of pathogen driven host-cell death to detect new anti-virulence drugs targeting Pseudomonas aeruginosa (Pa) and Salmonella enterica serovar Typhimurium (ST), both known for their emerging antibiotic resistance. By screening over 10,000 small molecules we could identify several substances showing promising effects on Pa and ST pathogenicity in our in vitro infection model. Importantly, we could detect compounds potently inhibiting bacteria induced killing of host cells and one novel comipound with impact on the function of the type 3 secretion system (T3SS) of ST. Thus, we provide proof of concept data of rapid and feasible medium- to high-throughput drug screening assays targeting virulence mechanisms of two major Gram-negative pathogens.
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spelling pubmed-74635802020-09-02 Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium von Ambüren, Julia Schreiber, Fynn Fischer, Julia Winter, Sandra van Gumpel, Edeltraud Simonis, Alexander Rybniker, Jan Microorganisms Article The prevalence of bacterial pathogens being resistant to antibiotic treatment is increasing worldwide, leading to a severe global health challenge. Simultaneously, the development and approval of new antibiotics stagnated in the past decades, leading to an urgent need for novel approaches to avoid the spread of untreatable bacterial infections in the future. We developed a highly comprehensive screening platform based on quantification of pathogen driven host-cell death to detect new anti-virulence drugs targeting Pseudomonas aeruginosa (Pa) and Salmonella enterica serovar Typhimurium (ST), both known for their emerging antibiotic resistance. By screening over 10,000 small molecules we could identify several substances showing promising effects on Pa and ST pathogenicity in our in vitro infection model. Importantly, we could detect compounds potently inhibiting bacteria induced killing of host cells and one novel comipound with impact on the function of the type 3 secretion system (T3SS) of ST. Thus, we provide proof of concept data of rapid and feasible medium- to high-throughput drug screening assays targeting virulence mechanisms of two major Gram-negative pathogens. MDPI 2020-07-22 /pmc/articles/PMC7463580/ /pubmed/32707871 http://dx.doi.org/10.3390/microorganisms8081096 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
von Ambüren, Julia
Schreiber, Fynn
Fischer, Julia
Winter, Sandra
van Gumpel, Edeltraud
Simonis, Alexander
Rybniker, Jan
Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium
title Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium
title_full Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium
title_fullStr Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium
title_full_unstemmed Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium
title_short Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium
title_sort comprehensive host cell-based screening assays for identification of anti-virulence drugs targeting pseudomonas aeruginosa and salmonella typhimurium
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463580/
https://www.ncbi.nlm.nih.gov/pubmed/32707871
http://dx.doi.org/10.3390/microorganisms8081096
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