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Activity of novel inhibitors of Staphylococcus aureus biofilms

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Abstract

Staphylococcus aureus is one of the most important pathogens causing chronic biofilm infections. These are becoming more difficult to treat owing to drug resistance, particularly because S. aureus biofilms limit the efficacy of antimicrobial agents, leading to high morbidity and mortality. In the present study, we screened for inhibitors of S. aureus biofilm formation using a natural product library from the Korea Chemical Bank (KCB). Screening by crystal violet-based biomass staining assay identified hit compounds. Further examination of antibiofilm properties of these compounds was conducted and led to the identification of celastrol and telithromycin. In vitro, both celastrol and telithromycin were toxic to planktonic S. aureus and also active against a clinical methicillin-resistant S. aureus (MRSA) isolate. The effect of the compounds on preformed biofilms of clinical MRSA isolates was evaluated by confocal laser scanning microscopy (CLSM), which revealed the absence of typical biofilm architecture. In addition, celastrol and telithromycin inhibited the production of extracellular protein at selected sub-MIC concentrations, which revealed the reduced extracellular polymeric substance (EPS) secretion. Celastrol exhibited greater cytotoxicity than telithromycin. These data suggest that the hit compounds, especially telithromycin, could be considered novel inhibitors of S. aureus biofilm. Although the mechanisms of the effects on S. aureus biofilms are not fully understood, our data suggest that telithromycin could be a useful adjuvant therapeutic agent for S. aureus biofilm-related infections.

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Acknowledgements

This study was supported by the Soonchunhyang University Research Fund and by Basic Science Research Program, through the National Research Foundation of Korea, funded by the Ministry of Education (NRF-2015R1D1A1A02061773).

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Authors and Affiliations

  1. Department of Medical Science, College of Medical Sciences, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si, Chungcheongnam-do, 31538, Republic of Korea

    Seung-Gyun Woo, So-Yeon Lee & Yong-Bin Eom

  2. Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si, Chungcheongnam-do, 31538, Republic of Korea

    So-Min Lee, Kyoung-Hee Lim, Eun-Ju Ha & Yong-Bin Eom

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  1. Seung-Gyun Woo
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  2. So-Yeon Lee
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  3. So-Min Lee
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  4. Kyoung-Hee Lim
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Correspondence to Yong-Bin Eom.

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Electronic supplementary material

Fig. S1

Representation of high-throughput screening for inhibitors of S. aureus ATCC 29213 biofilm formation. After screening at 250 μmol/L, compound activities were confirmed at 5 μmol/L (a). Results are expressed as percentage inhibition compared with controls lacking the compound. Triangle and square symbols indicate celastrol and telithromycin, respectively. Chemical structures of celastrol (left) and telithromycin (right) (b) (GIF 170 kb)

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Woo, SG., Lee, SY., Lee, SM. et al. Activity of novel inhibitors of Staphylococcus aureus biofilms. Folia Microbiol 62, 157–167 (2017). https://doi.org/10.1007/s12223-016-0485-4

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  • DOI: https://doi.org/10.1007/s12223-016-0485-4

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