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

  • Sci Rep. 2018 Feb 9;8(1):2758. doi: 10.1038/s41598-018-21141-2.
Cin Kong  1  2 ,  Chin-Fei Chee  3 ,  Katharina Richter  4  5 ,  Nicky Thomas  5  6 ,  Noorsaadah Abd Rahman  7 ,  Sheila Nathan  8
Affiliations
  • 1. School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi Selangor, Malaysia.
  • 2. Department of Biomedical Sciences, Faculty of Science, University of Nottingham Malaysia Campus, 43500, Semenyih, Selangor, Malaysia.
  • 3. Nanotechnology & Catalysis Research Centre, University of Malaya, 50603, Kuala Lumpur, Malaysia.
  • 4. Department of Surgery, Basil Hetzel Institute for Translational Health Research, The University of Adelaide, Adelaide, South Australia, Australia.
  • 5. Adelaide Biofilm Test Facility, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
  • 6. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
  • 7. Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
  • 8. School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi Selangor, Malaysia. [email protected].
PMID: 29426873 DOI: 10.1038/s41598-018-21141-2
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.

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