Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162

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...

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Bibliographic Details
Published in:Scientific reports 2018-02, Vol.8 (1), p.2758-16, Article 2758
Main Authors: Kong, Cin, Chee, Chin-Fei, Richter, Katharina, Thomas, Nicky, Abd Rahman, Noorsaadah, Nathan, Sheila
Format: Article
Language:English
Subjects:
Antibiotic resistance
Antibiotics
Benzimidazoles
Biochemical analysis
Biofilms
Gene expression
Genomes
Gram-positive bacteria
Hemolysins
Nosocomial infection
Nosocomial infections
Pathogens
Penicillin
Staphylococcus aureus
Virulence factors
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-21141-2