New Life of an Old Drug: Caffeine as a Modulator of Antibacterial Activity of Commonly Used Antibiotics
With the rapid and continuous emergence of antimicrobial resistance, bacterial infections became a significant global healthcare concern. One of the proposed strategies to combat multidrug-resistant pathogens is to use additional compounds, such as natural biologically active substances, as adjuvant...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/7/872 |
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| author | Anna Woziwodzka Marta Krychowiak-Maśnicka Grzegorz Gołuński Anna Łosiewska Agnieszka Borowik Dariusz Wyrzykowski Jacek Piosik |
| author_facet | Anna Woziwodzka Marta Krychowiak-Maśnicka Grzegorz Gołuński Anna Łosiewska Agnieszka Borowik Dariusz Wyrzykowski Jacek Piosik |
| author_sort | Anna Woziwodzka |
| collection | DOAJ |
| description | With the rapid and continuous emergence of antimicrobial resistance, bacterial infections became a significant global healthcare concern. One of the proposed strategies to combat multidrug-resistant pathogens is to use additional compounds, such as natural biologically active substances, as adjuvants for existing antibiotics. In this study, we investigated the potential of caffeine, the widely consumed alkaloid, to modulate the antibacterial effects of antibiotics commonly used in clinical practice. We used disc diffusion assay to evaluate the effects of caffeine on 40 antibiotics in two <i>Staphylococcus aureus</i> strains (methicillin-resistant and methicillin-sensitive). Based on the results of this step, we selected five antibiotics for which the greatest caffeine-induced improvements in antibacterial activity were observed, and further analyzed their interactions with caffeine using a checkerboard approach. Caffeine at concentrations of 250 µg/mL or higher halved the MIC values of ticarcillin, cefepime, gentamycin, azithromycin, and novobiocin for all gram-negative species investigated (<i>Pseudomonas aeruginosa</i>, <i>Klebsiella pneumoniae</i>, and <i>Acinetobacter baumannii</i>). At the highest caffeine concentrations tested (up to 16 mg/mL), decreases in MIC values were 8- to 16-fold. The obtained results prove that caffeine modulates the activity of structurally diverse antibiotics, with the most promising synergistic effects observed for cefepime and azithromycin toward gram-negative pathogens. |
| first_indexed | 2024-03-09T13:11:38Z |
| format | Article |
| id | doaj.art-728867fc5f464aa78db4c394db187391 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T13:11:38Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-728867fc5f464aa78db4c394db1873912023-11-30T21:40:39ZengMDPI AGPharmaceuticals1424-82472022-07-0115787210.3390/ph15070872New Life of an Old Drug: Caffeine as a Modulator of Antibacterial Activity of Commonly Used AntibioticsAnna Woziwodzka0Marta Krychowiak-Maśnicka1Grzegorz Gołuński2Anna Łosiewska3Agnieszka Borowik4Dariusz Wyrzykowski5Jacek Piosik6Laboratory of Biophysics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, PolandLaboratory of Biologically Active Compounds, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, PolandLaboratory of Biophysics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, PolandLaboratory of Biophysics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, PolandLaboratory of Biophysics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, PolandDepartment of Inorganic Biological Chemistry, Faculty of Chemistry, University of Gdansk, 80-308 Gdansk, PolandLaboratory of Biophysics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, PolandWith the rapid and continuous emergence of antimicrobial resistance, bacterial infections became a significant global healthcare concern. One of the proposed strategies to combat multidrug-resistant pathogens is to use additional compounds, such as natural biologically active substances, as adjuvants for existing antibiotics. In this study, we investigated the potential of caffeine, the widely consumed alkaloid, to modulate the antibacterial effects of antibiotics commonly used in clinical practice. We used disc diffusion assay to evaluate the effects of caffeine on 40 antibiotics in two <i>Staphylococcus aureus</i> strains (methicillin-resistant and methicillin-sensitive). Based on the results of this step, we selected five antibiotics for which the greatest caffeine-induced improvements in antibacterial activity were observed, and further analyzed their interactions with caffeine using a checkerboard approach. Caffeine at concentrations of 250 µg/mL or higher halved the MIC values of ticarcillin, cefepime, gentamycin, azithromycin, and novobiocin for all gram-negative species investigated (<i>Pseudomonas aeruginosa</i>, <i>Klebsiella pneumoniae</i>, and <i>Acinetobacter baumannii</i>). At the highest caffeine concentrations tested (up to 16 mg/mL), decreases in MIC values were 8- to 16-fold. The obtained results prove that caffeine modulates the activity of structurally diverse antibiotics, with the most promising synergistic effects observed for cefepime and azithromycin toward gram-negative pathogens.https://www.mdpi.com/1424-8247/15/7/872antibacterial agentantimicrobial resistanceazithromycincaffeinecefepimedrug repositioning |
| spellingShingle | Anna Woziwodzka Marta Krychowiak-Maśnicka Grzegorz Gołuński Anna Łosiewska Agnieszka Borowik Dariusz Wyrzykowski Jacek Piosik New Life of an Old Drug: Caffeine as a Modulator of Antibacterial Activity of Commonly Used Antibiotics Pharmaceuticals antibacterial agent antimicrobial resistance azithromycin caffeine cefepime drug repositioning |
| title | New Life of an Old Drug: Caffeine as a Modulator of Antibacterial Activity of Commonly Used Antibiotics |
| title_full | New Life of an Old Drug: Caffeine as a Modulator of Antibacterial Activity of Commonly Used Antibiotics |
| title_fullStr | New Life of an Old Drug: Caffeine as a Modulator of Antibacterial Activity of Commonly Used Antibiotics |
| title_full_unstemmed | New Life of an Old Drug: Caffeine as a Modulator of Antibacterial Activity of Commonly Used Antibiotics |
| title_short | New Life of an Old Drug: Caffeine as a Modulator of Antibacterial Activity of Commonly Used Antibiotics |
| title_sort | new life of an old drug caffeine as a modulator of antibacterial activity of commonly used antibiotics |
| topic | antibacterial agent antimicrobial resistance azithromycin caffeine cefepime drug repositioning |
| url | https://www.mdpi.com/1424-8247/15/7/872 |
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