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

Cin Kong, Chin Fei Chee, Katharina Richter, Nicky Thomas, Noorsaadah Abd Rahman, Sheila Nathan

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Number of pages1
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 9 Feb 2018

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Biofilms
Virulence
Staphylococcus aureus
Genes
Anti-Bacterial Agents
Microbial Viability
Hemolysin Proteins
benzimidazole
Gene Expression Profiling
Virulence Factors
Cross Infection
Infection
Peptide Hydrolases
Genome
Bacteria

ASJC Scopus subject areas

  • General

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Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162. / Kong, Cin; Chee, Chin Fei; Richter, Katharina; Thomas, Nicky; Abd Rahman, Noorsaadah; Nathan, Sheila.

In: Scientific reports, Vol. 8, No. 1, 09.02.2018.

Research output: Contribution to journalArticle

Kong, Cin ; Chee, Chin Fei ; Richter, Katharina ; Thomas, Nicky ; Abd Rahman, Noorsaadah ; Nathan, Sheila. / Suppression of Staphylococcus aureus biofilm formation and virulence by a benzimidazole derivative, UM-C162. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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