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Open AccessArticle

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

1
Department I of Internal Medicine, University of Cologne, 50937 Cologne, Germany
2
Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany
3
German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 50937 Cologne, Germany
*
Authors to whom correspondence should be addressed.
Both authors contributed equally and should be considered as first authors.
Both authors contributed equally and should be considered as senior authors.
Microorganisms 2020, 8(8), 1096; https://doi.org/10.3390/microorganisms8081096
Received: 7 July 2020 / Revised: 14 July 2020 / Accepted: 20 July 2020 / Published: 22 July 2020
(This article belongs to the Section Antimicrobial Agents and Resistance)
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. View Full-Text
Keywords: multidrug-resistant pathogens; host-directed therapies; antibiotic drug screening; Salmonella Typhimurium; Pseudomonas aeruginosa; type 3 secretion system; antibiotic resistance multidrug-resistant pathogens; host-directed therapies; antibiotic drug screening; Salmonella Typhimurium; Pseudomonas aeruginosa; type 3 secretion system; antibiotic resistance
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MDPI and ACS Style

von Ambüren, J.; Schreiber, F.; Fischer, J.; Winter, S.; van Gumpel, E.; Simonis, A.; Rybniker, J. Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium. Microorganisms 2020, 8, 1096. https://doi.org/10.3390/microorganisms8081096

AMA Style

von Ambüren J, Schreiber F, Fischer J, Winter S, van Gumpel E, Simonis A, Rybniker J. Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium. Microorganisms. 2020; 8(8):1096. https://doi.org/10.3390/microorganisms8081096

Chicago/Turabian Style

von Ambüren, Julia; Schreiber, Fynn; Fischer, Julia; Winter, Sandra; van Gumpel, Edeltraud; Simonis, Alexander; Rybniker, Jan. 2020. "Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium" Microorganisms 8, no. 8: 1096. https://doi.org/10.3390/microorganisms8081096

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