Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies
Abstract Background Antimicrobial resistance is growing substantially, which necessitates the search for novel therapeutic options. Terbinafine, an allylamine antifungal agent that exhibits a broad spectrum of activity and is used in the treatment of dermatophytosis, could be a possible option to di...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Annals of Clinical Microbiology and Antimicrobials |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12941-022-00513-7 |
| _version_ | 1817970593195098112 |
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| author | Momen Askoura Nehal Yousef Basem Mansour Fatma Al-zahraa A. Yehia |
| author_facet | Momen Askoura Nehal Yousef Basem Mansour Fatma Al-zahraa A. Yehia |
| author_sort | Momen Askoura |
| collection | DOAJ |
| description | Abstract Background Antimicrobial resistance is growing substantially, which necessitates the search for novel therapeutic options. Terbinafine, an allylamine antifungal agent that exhibits a broad spectrum of activity and is used in the treatment of dermatophytosis, could be a possible option to disarm S. aureus virulence. Methods Terbinafine inhibitory effect on staphyloxanthin was characterized by quantitative measurement of staphyloxanthin intermediates and molecular docking. The effect of terbinafine on S. aureus stress survival was characterized by viable counting. The anti-biofilm activity of terbinafine on S. aureus was assessed by the crystal violet assay and microscopy. Changes in S. aureus membrane following treatment with terbinafine were determined using Fourier transform infrared (FTIR) analysis. The synergistic action of terbinafine in combination with conventional antibiotics was characterized using the checkerboard assay. qRT-PCR was used to evaluate the impact of terbinafine on S. aureus gene expression. The influence of terbinafine on S. aureus pathogenesis was investigated in mice infection model. Results Terbinafine inhibits staphyloxanthin biosynthesis through targeting dehydrosqualene desaturase (CrtN). Docking analysis of terbinafine against the predicted active site of CrtN reveals a binding energy of − 9.579 kcal/mol exemplified by the formation of H-bonds, H-arene bonds, and hydrophobic/hydrophilic interactions with the conserved amino acids of the receptor pocket. Terbinafine treated S. aureus was more susceptible to both oxidative and acid stress as well as human blood killing as compared to untreated cells. Targeting staphyloxanthin by terbinafine rendered S. aureus more sensitive to membrane acting antibiotics. Terbinafine interfered with S. aureus biofilm formation through targeting cell autoaggregation, hydrophobicity, and exopolysaccharide production. Moreover, terbinafine demonstrated a synergistic interaction against S. aureus when combined with conventional antibiotics. Importantly, terbinafine attenuated S. aureus pathogenesis using mice infection model. qRT-PCR revealed that terbinafine repressed expression of the transcriptional regulators sigB, sarA, and msaB, as well as icaA in S. aureus. Conclusions Present findings strongly suggest that terbinafine could be used safely and efficiently as an anti-virulent agent to combat S. aureus infections. |
| first_indexed | 2024-04-13T20:37:01Z |
| format | Article |
| id | doaj.art-6bc3c63b3705426391af9207c6401b34 |
| institution | Directory Open Access Journal |
| issn | 1476-0711 |
| language | English |
| last_indexed | 2024-04-13T20:37:01Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Annals of Clinical Microbiology and Antimicrobials |
| spelling | doaj.art-6bc3c63b3705426391af9207c6401b342022-12-22T02:31:01ZengBMCAnnals of Clinical Microbiology and Antimicrobials1476-07112022-05-0121111710.1186/s12941-022-00513-7Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studiesMomen Askoura0Nehal Yousef1Basem Mansour2Fatma Al-zahraa A. Yehia3Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig UniversityDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig UniversityDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Delta University for Science and TechnologyDepartment of Microbiology and Immunology, Faculty of Pharmacy, Zagazig UniversityAbstract Background Antimicrobial resistance is growing substantially, which necessitates the search for novel therapeutic options. Terbinafine, an allylamine antifungal agent that exhibits a broad spectrum of activity and is used in the treatment of dermatophytosis, could be a possible option to disarm S. aureus virulence. Methods Terbinafine inhibitory effect on staphyloxanthin was characterized by quantitative measurement of staphyloxanthin intermediates and molecular docking. The effect of terbinafine on S. aureus stress survival was characterized by viable counting. The anti-biofilm activity of terbinafine on S. aureus was assessed by the crystal violet assay and microscopy. Changes in S. aureus membrane following treatment with terbinafine were determined using Fourier transform infrared (FTIR) analysis. The synergistic action of terbinafine in combination with conventional antibiotics was characterized using the checkerboard assay. qRT-PCR was used to evaluate the impact of terbinafine on S. aureus gene expression. The influence of terbinafine on S. aureus pathogenesis was investigated in mice infection model. Results Terbinafine inhibits staphyloxanthin biosynthesis through targeting dehydrosqualene desaturase (CrtN). Docking analysis of terbinafine against the predicted active site of CrtN reveals a binding energy of − 9.579 kcal/mol exemplified by the formation of H-bonds, H-arene bonds, and hydrophobic/hydrophilic interactions with the conserved amino acids of the receptor pocket. Terbinafine treated S. aureus was more susceptible to both oxidative and acid stress as well as human blood killing as compared to untreated cells. Targeting staphyloxanthin by terbinafine rendered S. aureus more sensitive to membrane acting antibiotics. Terbinafine interfered with S. aureus biofilm formation through targeting cell autoaggregation, hydrophobicity, and exopolysaccharide production. Moreover, terbinafine demonstrated a synergistic interaction against S. aureus when combined with conventional antibiotics. Importantly, terbinafine attenuated S. aureus pathogenesis using mice infection model. qRT-PCR revealed that terbinafine repressed expression of the transcriptional regulators sigB, sarA, and msaB, as well as icaA in S. aureus. Conclusions Present findings strongly suggest that terbinafine could be used safely and efficiently as an anti-virulent agent to combat S. aureus infections.https://doi.org/10.1186/s12941-022-00513-7Staphylococcus aureusTerbinafineStaphyloxanthinBiofilmVirulence |
| spellingShingle | Momen Askoura Nehal Yousef Basem Mansour Fatma Al-zahraa A. Yehia Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies Annals of Clinical Microbiology and Antimicrobials Staphylococcus aureus Terbinafine Staphyloxanthin Biofilm Virulence |
| title | Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies |
| title_full | Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies |
| title_fullStr | Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies |
| title_full_unstemmed | Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies |
| title_short | Antibiofilm and staphyloxanthin inhibitory potential of terbinafine against Staphylococcus aureus: in vitro and in vivo studies |
| title_sort | antibiofilm and staphyloxanthin inhibitory potential of terbinafine against staphylococcus aureus in vitro and in vivo studies |
| topic | Staphylococcus aureus Terbinafine Staphyloxanthin Biofilm Virulence |
| url | https://doi.org/10.1186/s12941-022-00513-7 |
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