Efflux Pump Inhibition and Resistance Modulation in <i>Mycobacterium smegmatis</i> by <i>Peucedanum ostruthium</i> and Its Coumarins
Antibiotic resistance is a growing problem and may become the next major global health crisis if no timely actions are taken. Mycobacterial infections are widespread and, due to antibiotic resistance, also hard to treat and a major cause of mortality. Natural compounds have the potential to increase...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/9/1075 |
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| author | Katarina Šimunović Julia Solnier Fabian Alperth Olaf Kunert Sonja Smole Možina Franz Bucar |
| author_facet | Katarina Šimunović Julia Solnier Fabian Alperth Olaf Kunert Sonja Smole Možina Franz Bucar |
| author_sort | Katarina Šimunović |
| collection | DOAJ |
| description | Antibiotic resistance is a growing problem and may become the next major global health crisis if no timely actions are taken. Mycobacterial infections are widespread and, due to antibiotic resistance, also hard to treat and a major cause of mortality. Natural compounds have the potential to increase antibiotic effectiveness due to their resistance modulatory and antimicrobial effects. In this study, <i>Peucedanum ostruthium</i> extracts, fractions, and isolated compounds were investigated regarding their antimicrobial and resistance-modulatory effects as well as efflux pump inhibition in <i>Mycobacterium smegmatis.</i> <i>P. ostruthium</i> extracts were found to have anti-mycobacterial potential and resistance modulating effects on ethidium bromide activity. The major antibacterial effect was attributed to ostruthin, and we found that the more lipophilic the substrate, the greater the antimicrobial effect. Imperatorin caused potent modulatory effects by interfering with the action of the major LfrA efflux pump in <i>M. smegmatis</i>. The plant <i>P. ostruthuim</i> has a complex effect on <i>M. smegmatis,</i> including antibacterial, efflux pump inhibition, resistance modulation, and membrane permeabilization, and its major constituents, ostruthin and imperatorin, have a distinct role in these effects. This makes <i>P. ostruthium</i> and its coumarins promising therapeutics to consider in the fight against drug-resistant mycobacteria. |
| first_indexed | 2024-03-10T07:56:54Z |
| format | Article |
| id | doaj.art-337272e85a074df197498fff4c700d73 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T07:56:54Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-337272e85a074df197498fff4c700d732023-11-22T11:45:52ZengMDPI AGAntibiotics2079-63822021-09-01109107510.3390/antibiotics10091075Efflux Pump Inhibition and Resistance Modulation in <i>Mycobacterium smegmatis</i> by <i>Peucedanum ostruthium</i> and Its CoumarinsKatarina Šimunović0Julia Solnier1Fabian Alperth2Olaf Kunert3Sonja Smole Možina4Franz Bucar5Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Beethovenstraße 8, 8010 Graz, AustriaDepartment of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Beethovenstraße 8, 8010 Graz, AustriaDepartment of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Beethovenstraße 8, 8010 Graz, AustriaDepartment of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Beethovenstraße 8, 8010 Graz, AustriaDepartment of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, 1000 Ljubljana, SloveniaDepartment of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, Beethovenstraße 8, 8010 Graz, AustriaAntibiotic resistance is a growing problem and may become the next major global health crisis if no timely actions are taken. Mycobacterial infections are widespread and, due to antibiotic resistance, also hard to treat and a major cause of mortality. Natural compounds have the potential to increase antibiotic effectiveness due to their resistance modulatory and antimicrobial effects. In this study, <i>Peucedanum ostruthium</i> extracts, fractions, and isolated compounds were investigated regarding their antimicrobial and resistance-modulatory effects as well as efflux pump inhibition in <i>Mycobacterium smegmatis.</i> <i>P. ostruthium</i> extracts were found to have anti-mycobacterial potential and resistance modulating effects on ethidium bromide activity. The major antibacterial effect was attributed to ostruthin, and we found that the more lipophilic the substrate, the greater the antimicrobial effect. Imperatorin caused potent modulatory effects by interfering with the action of the major LfrA efflux pump in <i>M. smegmatis</i>. The plant <i>P. ostruthuim</i> has a complex effect on <i>M. smegmatis,</i> including antibacterial, efflux pump inhibition, resistance modulation, and membrane permeabilization, and its major constituents, ostruthin and imperatorin, have a distinct role in these effects. This makes <i>P. ostruthium</i> and its coumarins promising therapeutics to consider in the fight against drug-resistant mycobacteria.https://www.mdpi.com/2079-6382/10/9/1075<i>Mycobacterium smegmatis</i>efflux pump inhibitor<i>Peucedanum ostruthium</i>antibacterialostruthinimperatorin |
| spellingShingle | Katarina Šimunović Julia Solnier Fabian Alperth Olaf Kunert Sonja Smole Možina Franz Bucar Efflux Pump Inhibition and Resistance Modulation in <i>Mycobacterium smegmatis</i> by <i>Peucedanum ostruthium</i> and Its Coumarins Antibiotics <i>Mycobacterium smegmatis</i> efflux pump inhibitor <i>Peucedanum ostruthium</i> antibacterial ostruthin imperatorin |
| title | Efflux Pump Inhibition and Resistance Modulation in <i>Mycobacterium smegmatis</i> by <i>Peucedanum ostruthium</i> and Its Coumarins |
| title_full | Efflux Pump Inhibition and Resistance Modulation in <i>Mycobacterium smegmatis</i> by <i>Peucedanum ostruthium</i> and Its Coumarins |
| title_fullStr | Efflux Pump Inhibition and Resistance Modulation in <i>Mycobacterium smegmatis</i> by <i>Peucedanum ostruthium</i> and Its Coumarins |
| title_full_unstemmed | Efflux Pump Inhibition and Resistance Modulation in <i>Mycobacterium smegmatis</i> by <i>Peucedanum ostruthium</i> and Its Coumarins |
| title_short | Efflux Pump Inhibition and Resistance Modulation in <i>Mycobacterium smegmatis</i> by <i>Peucedanum ostruthium</i> and Its Coumarins |
| title_sort | efflux pump inhibition and resistance modulation in i mycobacterium smegmatis i by i peucedanum ostruthium i and its coumarins |
| topic | <i>Mycobacterium smegmatis</i> efflux pump inhibitor <i>Peucedanum ostruthium</i> antibacterial ostruthin imperatorin |
| url | https://www.mdpi.com/2079-6382/10/9/1075 |
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