13
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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. elegansS. 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.

          Related collections

          Most cited references45

          • Record: found
          • Abstract: found
          • Article: not found

          Growing and analyzing static biofilms.

          Many bacteria can exist as surface-attached aggregations known as biofilms. Presented in this unit are several approaches for the study of these communities. The focus here is on static biofilm systems, which are particularly useful for examination of the early stages of biofilm formation, including initial adherence to the surface and microcolony formation. Furthermore, most of the techniques presented are easily adapted to the study of biofilms under a variety of conditions and are suitable for either small- or relatively large-scale studies. Unlike assays involving continuous-flow systems, the static biofilm assays described here require very little specialized equipment and are relatively simple to execute. In addition, these static biofilm systems allow analysis of biofilm formation with a variety of readouts, including microscopy of live cells, macroscopic visualization of stained bacteria, and viability counts. Used individually or in combination, these assays provide useful means for the study of biofilms.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Targeting virulence: can we make evolution-proof drugs?

            Antivirulence drugs are a new type of therapeutic drug that target virulence factors, potentially revitalising the drug-development pipeline with new targets. As antivirulence drugs disarm the pathogen, rather than kill or halt pathogen growth, it has been hypothesized that they will generate much weaker selection for resistance than traditional antibiotics. However, recent studies have shown that mechanisms of resistance to antivirulence drugs exist, seemingly damaging the 'evolution-proof' claim. In this Opinion article, we highlight a crucial distinction between whether resistance can emerge and whether it will spread to a high frequency under drug selection. We argue that selection for resistance can be reduced, or even reversed, using appropriate combinations of target and treatment environment, opening a path towards the development of evolutionarily robust novel therapeutics.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Surface protein adhesins of Staphylococcus aureus.

              T. Foster (1998)
              Staphylococcus aureus can colonize the host to initiate infection by adhering to components of the extracellular matrix. Adherence is mediated by surface protein adhesins (MSCRAMMs). Ligand binding by these fibronectin-, fibrinogen- and collagen-binding proteins occurs by distinct mechanisms that are being investigated at the molecular level.
                Bookmark

                Author and article information

                Contributors
                sheila@ukm.edu.my
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                9 February 2018
                9 February 2018
                2018
                : 8
                : 2758
                Affiliations
                [1 ]ISNI 0000 0004 1937 1557, GRID grid.412113.4, School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, ; 43600 UKM Bangi Selangor, Malaysia
                [2 ]ISNI 0000 0001 2308 5949, GRID grid.10347.31, Nanotechnology & Catalysis Research Centre, University of Malaya, ; 50603 Kuala Lumpur, Malaysia
                [3 ]ISNI 0000 0004 1936 7304, GRID grid.1010.0, Department of Surgery, Basil Hetzel Institute for Translational Health Research, The University of Adelaide, ; Adelaide, South Australia Australia
                [4 ]ISNI 0000 0000 8994 5086, GRID grid.1026.5, Adelaide Biofilm Test Facility, Sansom Institute for Health Research, University of South Australia, ; Adelaide, South Australia Australia
                [5 ]ISNI 0000 0000 8994 5086, GRID grid.1026.5, School of Pharmacy and Medical Sciences, University of South Australia, ; Adelaide, South Australia Australia
                [6 ]ISNI 0000 0001 2308 5949, GRID grid.10347.31, Department of Chemistry, , Faculty of Science, University of Malaya, ; 50603 Kuala Lumpur, Malaysia
                [7 ]GRID grid.440435.2, Present Address: Department of Biomedical Sciences, , Faculty of Science, University of Nottingham Malaysia Campus, ; 43500 Semenyih, Selangor Malaysia
                Author information
                http://orcid.org/0000-0002-5650-9119
                http://orcid.org/0000-0002-2132-2346
                Article
                21141
                10.1038/s41598-018-21141-2
                5807447
                29426873
                eee3a4f5-8081-4a95-8bdc-2998ce89c305
                © The Author(s) 2018

                Open Access 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/.

                History
                : 17 November 2017
                : 30 January 2018
                Categories
                Article
                Custom metadata
                © The Author(s) 2018

                Uncategorized
                Uncategorized

                Comments

                Comment on this article