Bakuchiol kills Staphylococcus aureus persisters and potentiates colistin activity against Acinetobacter baumannii persisters
Infections associated with bacterial persisters are challenging to cure because they can evade antibiotics and regrow, often resulting in relapse. Current antibiotics are not optimized to target persisters, highlighting the urgent need for new therapeutics. Here, we report that bakuchiol, a plant-de...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1592183/full |
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| author | Kayeong Suh Yeju Lee Seongeun Baek Jin Kim Jinbeom Seo Yung-Hun Yang Jae-Seok Kim Wonsik Lee Eun Kyoung Seo Wooseong Kim |
| author_facet | Kayeong Suh Yeju Lee Seongeun Baek Jin Kim Jinbeom Seo Yung-Hun Yang Jae-Seok Kim Wonsik Lee Eun Kyoung Seo Wooseong Kim |
| author_sort | Kayeong Suh |
| collection | DOAJ |
| description | Infections associated with bacterial persisters are challenging to cure because they can evade antibiotics and regrow, often resulting in relapse. Current antibiotics are not optimized to target persisters, highlighting the urgent need for new therapeutics. Here, we report that bakuchiol, a plant-derived natural product, exhibits anti-persister and adjuvant properties. Bakuchiol eradicates persisters formed by the gram-positive bacterium Staphylococcus aureus at 8 μg/mL and, in combination with 1 μg/mL colistin, completely eliminates persisters formed by the gram-negative bacterium Acinetobacter baumannii. Mechanistic analyses revealed that bakuchiol selectively disrupted bacterial membrane phospholipids while sparing mammalian membranes and exhibited low cytotoxicity. In Acinetobacter baumannii persisters, bakuchiol likely damages phospholipid patches in the outer membrane, causing nominal lethality but facilitating membrane permeabilization. This activity synergizes with colistin, which targets the lipooligosaccharide layer, resulting in the mutual reinforcement of their bactericidal effects. These findings highlight the potential of dual glycolipid–phospholipid targeting as a strategy to combat gram-negative persisters and highlight natural products as valuable sources for anti-persister therapeutics with membrane selectivity. |
| format | Article |
| id | doaj-art-4c5d2c4fa7f8441a8213cb6f92af179d |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-4c5d2c4fa7f8441a8213cb6f92af179d2025-08-20T03:10:06ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15921831592183Bakuchiol kills Staphylococcus aureus persisters and potentiates colistin activity against Acinetobacter baumannii persistersKayeong Suh0Yeju Lee1Seongeun Baek2Jin Kim3Jinbeom Seo4Yung-Hun Yang5Jae-Seok Kim6Wonsik Lee7Eun Kyoung Seo8Wooseong Kim9College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of KoreaCollege of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of KoreaCollege of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of KoreaCollege of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon, Republic of KoreaAdvanced Materials Program, Department of Biological Engineering, College of Engineering, Konkuk University, Seoul, Republic of KoreaDepartment of Laboratory Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon, Republic of KoreaCollege of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of KoreaCollege of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of KoreaInfections associated with bacterial persisters are challenging to cure because they can evade antibiotics and regrow, often resulting in relapse. Current antibiotics are not optimized to target persisters, highlighting the urgent need for new therapeutics. Here, we report that bakuchiol, a plant-derived natural product, exhibits anti-persister and adjuvant properties. Bakuchiol eradicates persisters formed by the gram-positive bacterium Staphylococcus aureus at 8 μg/mL and, in combination with 1 μg/mL colistin, completely eliminates persisters formed by the gram-negative bacterium Acinetobacter baumannii. Mechanistic analyses revealed that bakuchiol selectively disrupted bacterial membrane phospholipids while sparing mammalian membranes and exhibited low cytotoxicity. In Acinetobacter baumannii persisters, bakuchiol likely damages phospholipid patches in the outer membrane, causing nominal lethality but facilitating membrane permeabilization. This activity synergizes with colistin, which targets the lipooligosaccharide layer, resulting in the mutual reinforcement of their bactericidal effects. These findings highlight the potential of dual glycolipid–phospholipid targeting as a strategy to combat gram-negative persisters and highlight natural products as valuable sources for anti-persister therapeutics with membrane selectivity.https://www.frontiersin.org/articles/10.3389/fphar.2025.1592183/fullpersistersantibiotic resistancenatural productsMRSAAcinetobacterbaumannii |
| spellingShingle | Kayeong Suh Yeju Lee Seongeun Baek Jin Kim Jinbeom Seo Yung-Hun Yang Jae-Seok Kim Wonsik Lee Eun Kyoung Seo Wooseong Kim Bakuchiol kills Staphylococcus aureus persisters and potentiates colistin activity against Acinetobacter baumannii persisters Frontiers in Pharmacology persisters antibiotic resistance natural products MRSA Acinetobacterbaumannii |
| title | Bakuchiol kills Staphylococcus aureus persisters and potentiates colistin activity against Acinetobacter baumannii persisters |
| title_full | Bakuchiol kills Staphylococcus aureus persisters and potentiates colistin activity against Acinetobacter baumannii persisters |
| title_fullStr | Bakuchiol kills Staphylococcus aureus persisters and potentiates colistin activity against Acinetobacter baumannii persisters |
| title_full_unstemmed | Bakuchiol kills Staphylococcus aureus persisters and potentiates colistin activity against Acinetobacter baumannii persisters |
| title_short | Bakuchiol kills Staphylococcus aureus persisters and potentiates colistin activity against Acinetobacter baumannii persisters |
| title_sort | bakuchiol kills staphylococcus aureus persisters and potentiates colistin activity against acinetobacter baumannii persisters |
| topic | persisters antibiotic resistance natural products MRSA Acinetobacterbaumannii |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1592183/full |
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