Universität zu Köln

von Ambueren, Julia, Schreiber, Fynn, Fischer, Julia, Winter, Sandra, van Gumpel, Edeltraud, Simonis, Alexander ORCID: 0000-0003-2945-9897 and Rybniker, Jan (2020). Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs TargetingPseudomonas aeruginosaandSalmonellaTyphimurium. Microorganisms, 8 (8). BASEL: MDPI. ISSN 2076-2607

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Abstract

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 targetingPseudomonas aeruginosa(Pa) andSalmonella entericaserovar Typhimurium (ST), both known for their emerging antibiotic resistance. By screening over 10,000 small molecules we could identify several substances showing promising effects onPaandST 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) ofST. 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code von Ambueren, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Schreiber, Fynn UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Winter, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED van Gumpel, Edeltraud UNSPECIFIED UNSPECIFIED UNSPECIFIED Simonis, Alexander UNSPECIFIED orcid.org/0000-0003-2945-9897 UNSPECIFIED Rybniker, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-324567
DOI:	10.3390/microorganisms8081096
Journal or Publication Title:	Microorganisms
Volume:	8
Number:	8
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2076-2607
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PSEUDOMONAS-AERUGINOSA; INHIBITORS; DEFENSE; SYSTEM; INDOLE Multiple languages Microbiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32456