Real-time monitoring of biofilm growth identifies andrographolide as a potent antifungal compound eradicating Candida biofilms
Candida species cause life-threatening infections with high morbidity and mortality rates and their resistance to conventional therapy is closely linked to biofilm formation. Thus, the development of new approaches to study Candida biofilms and the identification of novel therapeutic strategies coul...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biofilm |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S259020752300031X |
| _version_ | 1797800996667129856 |
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| author | Miglė Žiemytė Juan C. Rodríguez-Díaz María P. Ventero-Martín Alex Mira María D. Ferrer |
| author_facet | Miglė Žiemytė Juan C. Rodríguez-Díaz María P. Ventero-Martín Alex Mira María D. Ferrer |
| author_sort | Miglė Žiemytė |
| collection | DOAJ |
| description | Candida species cause life-threatening infections with high morbidity and mortality rates and their resistance to conventional therapy is closely linked to biofilm formation. Thus, the development of new approaches to study Candida biofilms and the identification of novel therapeutic strategies could yield improved clinical outcomes. In the current study, we have set up an impedance-based in vitro system to study Candida spp. biofilms in real-time and to evaluate their sensitivity to two conventional antifungal groups used in clinical practice - azoles and echinocandins. Both fluconazole and voriconazole were unable to inhibit biofilm formation in most strains tested, while echinocandins showed biofilm inhibitory capacity at relatively low concentrations (starting from 0.625 mg/L). However, assays performed on 24 h Candida albicans and C. glabrata biofilms revealed that micafungin and caspofungin failed to eradicate mature biofilms at all tested concentrations, evidencing that once formed, Candida spp. biofilms are extremely difficult to eliminate using currently available antifungals. We then evaluated the antifungal and anti-biofilm effect of andrographolide, a natural compound isolated from the plant Andrographis paniculata with known antibiofilm activity on Gram-positive and Gram-negative bacteria. Optical density measures, impedance evaluation, CFU counts, and electron microscopy data showed that andrographolide strongly inhibits planktonic Candida spp. growth and halts Candida spp. biofilm formation in a dose-dependent manner in all tested strains. Moreover, andrographolide was capable of eliminating mature biofilms and viable cell numbers by up to 99.9% in the C. albicans and C. glabrata strains tested, suggesting its potential as a new approach to treat multi-resistant Candida spp. biofilm-related infections. |
| first_indexed | 2024-03-13T04:43:42Z |
| format | Article |
| id | doaj.art-bf9e77ca006540f9afd0f229471b29fa |
| institution | Directory Open Access Journal |
| issn | 2590-2075 |
| language | English |
| last_indexed | 2024-03-13T04:43:42Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biofilm |
| spelling | doaj.art-bf9e77ca006540f9afd0f229471b29fa2023-06-19T04:29:37ZengElsevierBiofilm2590-20752023-12-015100134Real-time monitoring of biofilm growth identifies andrographolide as a potent antifungal compound eradicating Candida biofilmsMiglė Žiemytė0Juan C. Rodríguez-Díaz1María P. Ventero-Martín2Alex Mira3María D. Ferrer4Genomics & Health Department, FISABIO Foundation, Valencia, SpainServicio de Microbiología, Hospital General Universitario de Alicante, ISABIAL, Alicante, SpainServicio de Microbiología, Hospital General Universitario de Alicante, ISABIAL, Alicante, SpainGenomics & Health Department, FISABIO Foundation, Valencia, Spain; CIBER Center for Epidemiology and Public Health (CIBER-ESP), Madrid, Spain; Corresponding author. FISABIO, Avda. Cataluña 21, 46020, Valencia, Spain.Genomics & Health Department, FISABIO Foundation, Valencia, SpainCandida species cause life-threatening infections with high morbidity and mortality rates and their resistance to conventional therapy is closely linked to biofilm formation. Thus, the development of new approaches to study Candida biofilms and the identification of novel therapeutic strategies could yield improved clinical outcomes. In the current study, we have set up an impedance-based in vitro system to study Candida spp. biofilms in real-time and to evaluate their sensitivity to two conventional antifungal groups used in clinical practice - azoles and echinocandins. Both fluconazole and voriconazole were unable to inhibit biofilm formation in most strains tested, while echinocandins showed biofilm inhibitory capacity at relatively low concentrations (starting from 0.625 mg/L). However, assays performed on 24 h Candida albicans and C. glabrata biofilms revealed that micafungin and caspofungin failed to eradicate mature biofilms at all tested concentrations, evidencing that once formed, Candida spp. biofilms are extremely difficult to eliminate using currently available antifungals. We then evaluated the antifungal and anti-biofilm effect of andrographolide, a natural compound isolated from the plant Andrographis paniculata with known antibiofilm activity on Gram-positive and Gram-negative bacteria. Optical density measures, impedance evaluation, CFU counts, and electron microscopy data showed that andrographolide strongly inhibits planktonic Candida spp. growth and halts Candida spp. biofilm formation in a dose-dependent manner in all tested strains. Moreover, andrographolide was capable of eliminating mature biofilms and viable cell numbers by up to 99.9% in the C. albicans and C. glabrata strains tested, suggesting its potential as a new approach to treat multi-resistant Candida spp. biofilm-related infections.http://www.sciencedirect.com/science/article/pii/S259020752300031XxCELLigenceFungal biofilmsAntifungalsCandida infectionsAndrographolideAntimicrobial resistance |
| spellingShingle | Miglė Žiemytė Juan C. Rodríguez-Díaz María P. Ventero-Martín Alex Mira María D. Ferrer Real-time monitoring of biofilm growth identifies andrographolide as a potent antifungal compound eradicating Candida biofilms Biofilm xCELLigence Fungal biofilms Antifungals Candida infections Andrographolide Antimicrobial resistance |
| title | Real-time monitoring of biofilm growth identifies andrographolide as a potent antifungal compound eradicating Candida biofilms |
| title_full | Real-time monitoring of biofilm growth identifies andrographolide as a potent antifungal compound eradicating Candida biofilms |
| title_fullStr | Real-time monitoring of biofilm growth identifies andrographolide as a potent antifungal compound eradicating Candida biofilms |
| title_full_unstemmed | Real-time monitoring of biofilm growth identifies andrographolide as a potent antifungal compound eradicating Candida biofilms |
| title_short | Real-time monitoring of biofilm growth identifies andrographolide as a potent antifungal compound eradicating Candida biofilms |
| title_sort | real time monitoring of biofilm growth identifies andrographolide as a potent antifungal compound eradicating candida biofilms |
| topic | xCELLigence Fungal biofilms Antifungals Candida infections Andrographolide Antimicrobial resistance |
| url | http://www.sciencedirect.com/science/article/pii/S259020752300031X |
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