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Type: Journal article
Title: Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162
Author: Kong, C.
Chee, C.-.F.
Richter, K.
Thomas, N.
Abd Rahman, N.
Nathan, S.
Citation: Scientific reports, 2018; 8(1):2758-1-2758-16
Publisher: Springer Nature
Issue Date: 2018
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Cin Kong, Chin-Fei Chee, Katharina Richter, Nicky Thomas, Noorsaadah Abd. Rahman and Sheila Nathan
Abstract: Staphylococcus aureus is a major cause of nosocomial infections and secretes a diverse spectrum of virulence determinants as well as forms biofilm. The emergence of antibiotic-resistant S. aureus highlights the need for alternative forms of therapeutics other than conventional antibiotics. One route to meet this need is screening small molecule derivatives for potential anti-infective activity. Using a previously optimized C. elegans - S. aureus small molecule screen, we identified a benzimidazole derivative, UM-C162, which rescued nematodes from a S. aureus infection. UM-C162 prevented the formation of biofilm in a dose-dependent manner without interfering with bacterial viability. To examine the effect of UM-C162 on the expression of S. aureus virulence genes, a genome-wide transcriptome analysis was performed on UM-C162-treated pathogen. Our data indicated that the genes associated with biofilm formation, particularly those involved in bacterial attachment, were suppressed in UM-C162-treated bacteria. Additionally, a set of genes encoding vital S. aureus virulence factors were also down-regulated in the presence of UM-C162. Further biochemical analysis validated that UM-C162-mediated disruption of S. aureus hemolysins, proteases and clumping factors production. Collectively, our findings propose that UM-C162 is a promising compound that can be further developed as an anti-virulence agent to control S. aureus infections.
Keywords: Antimicrobial resistance; biofilms
Rights: © The Author(s) 2018 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
RMID: 0030081802
DOI: 10.1038/s41598-018-21141-2
Grant ID: http://purl.org/au-research/grants/nhmrc/1090898
Appears in Collections:Medicine publications

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