Synergistic Antifungal Effect of Fluconazole Combined with Licofelone against Resistant Candida albicans
Candida albicans (C. albicans) is one of the important opportunistic fungal pathogens that is closely associated with disseminated or chronic infections. The objective of this study is to evaluate the synergistic antifungal effect of licofelone, which is dual microsomal prostaglandin E2 synthase/lip...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2017-11-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2017.02101/full |
| _version_ | 1818314331243151360 |
|---|---|
| author | Xinning Liu Xinning Liu Tao Li Decai Wang Yilei Yang Wenwen Sun Jianqiao Liu Shujuan Sun |
| author_facet | Xinning Liu Xinning Liu Tao Li Decai Wang Yilei Yang Wenwen Sun Jianqiao Liu Shujuan Sun |
| author_sort | Xinning Liu |
| collection | DOAJ |
| description | Candida albicans (C. albicans) is one of the important opportunistic fungal pathogens that is closely associated with disseminated or chronic infections. The objective of this study is to evaluate the synergistic antifungal effect of licofelone, which is dual microsomal prostaglandin E2 synthase/lipoxygenase (mPGES-1/LOX) inhibitor in combination with fluconazole against C. albicans. Here our results showed that licofelone (16 μg/mL) can synergistically work with fluconazole (1 μg/mL) against planktonic cells of fluconazole-resistant C. albicans. The two-drug combination inhibited the C. albicans biofilm formation over 12 h, and reduced the expression of extracellular phospholipase genes, biofilm-specific genes and RAS/cAMP/PKA pathway related genes. In addition, the two-drug combination inhibited the transition from yeast to hyphal growth form, and decreased the secreted aspartyl proteinase activity, while not affecting the drug efflux pumps activity. Galleria mellonella model was also used to confirm the antifungal activity of the drug combination in vivo. This study first indicates that the combination of fluconazole and licofelone has synergistic effect against resistant C. albicans and could be a promising therapeutic strategy for the antifungal treatment. |
| first_indexed | 2024-12-13T08:47:56Z |
| format | Article |
| id | doaj.art-ed5f0caea7f74687b71ed5b9f1361d8d |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-13T08:47:56Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-ed5f0caea7f74687b71ed5b9f1361d8d2022-12-21T23:53:25ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2017-11-01810.3389/fmicb.2017.02101300835Synergistic Antifungal Effect of Fluconazole Combined with Licofelone against Resistant Candida albicansXinning Liu0Xinning Liu1Tao Li2Decai Wang3Yilei Yang4Wenwen Sun5Jianqiao Liu6Shujuan Sun7Department of Clinical Pharmacy, Taishan Medical University, Taian, ChinaDepartment of Microbial and Biochemical Pharmacy, School of Medicine and Pharmacy, Ocean University of China, Qingdao, ChinaIntensive Care Unit, Qianfoshan Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Clinical Pharmacy, Taishan Medical University, Taian, ChinaDepartment of Pharmacy, Qianfoshan Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Clinical Pharmacy, Taishan Medical University, Taian, ChinaGeneral Practice, Shandong Provincial Hospital, Jinan, ChinaDepartment of Pharmacy, Qianfoshan Hospital Affiliated to Shandong University, Jinan, ChinaCandida albicans (C. albicans) is one of the important opportunistic fungal pathogens that is closely associated with disseminated or chronic infections. The objective of this study is to evaluate the synergistic antifungal effect of licofelone, which is dual microsomal prostaglandin E2 synthase/lipoxygenase (mPGES-1/LOX) inhibitor in combination with fluconazole against C. albicans. Here our results showed that licofelone (16 μg/mL) can synergistically work with fluconazole (1 μg/mL) against planktonic cells of fluconazole-resistant C. albicans. The two-drug combination inhibited the C. albicans biofilm formation over 12 h, and reduced the expression of extracellular phospholipase genes, biofilm-specific genes and RAS/cAMP/PKA pathway related genes. In addition, the two-drug combination inhibited the transition from yeast to hyphal growth form, and decreased the secreted aspartyl proteinase activity, while not affecting the drug efflux pumps activity. Galleria mellonella model was also used to confirm the antifungal activity of the drug combination in vivo. This study first indicates that the combination of fluconazole and licofelone has synergistic effect against resistant C. albicans and could be a promising therapeutic strategy for the antifungal treatment.http://journal.frontiersin.org/article/10.3389/fmicb.2017.02101/fullbiofilmscyclooxygenase (COX)drug resistance mechanismsenzyme inhibitorphospholipase |
| spellingShingle | Xinning Liu Xinning Liu Tao Li Decai Wang Yilei Yang Wenwen Sun Jianqiao Liu Shujuan Sun Synergistic Antifungal Effect of Fluconazole Combined with Licofelone against Resistant Candida albicans Frontiers in Microbiology biofilms cyclooxygenase (COX) drug resistance mechanisms enzyme inhibitor phospholipase |
| title | Synergistic Antifungal Effect of Fluconazole Combined with Licofelone against Resistant Candida albicans |
| title_full | Synergistic Antifungal Effect of Fluconazole Combined with Licofelone against Resistant Candida albicans |
| title_fullStr | Synergistic Antifungal Effect of Fluconazole Combined with Licofelone against Resistant Candida albicans |
| title_full_unstemmed | Synergistic Antifungal Effect of Fluconazole Combined with Licofelone against Resistant Candida albicans |
| title_short | Synergistic Antifungal Effect of Fluconazole Combined with Licofelone against Resistant Candida albicans |
| title_sort | synergistic antifungal effect of fluconazole combined with licofelone against resistant candida albicans |
| topic | biofilms cyclooxygenase (COX) drug resistance mechanisms enzyme inhibitor phospholipase |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2017.02101/full |
| work_keys_str_mv | AT xinningliu synergisticantifungaleffectoffluconazolecombinedwithlicofeloneagainstresistantcandidaalbicans AT xinningliu synergisticantifungaleffectoffluconazolecombinedwithlicofeloneagainstresistantcandidaalbicans AT taoli synergisticantifungaleffectoffluconazolecombinedwithlicofeloneagainstresistantcandidaalbicans AT decaiwang synergisticantifungaleffectoffluconazolecombinedwithlicofeloneagainstresistantcandidaalbicans AT yileiyang synergisticantifungaleffectoffluconazolecombinedwithlicofeloneagainstresistantcandidaalbicans AT wenwensun synergisticantifungaleffectoffluconazolecombinedwithlicofeloneagainstresistantcandidaalbicans AT jianqiaoliu synergisticantifungaleffectoffluconazolecombinedwithlicofeloneagainstresistantcandidaalbicans AT shujuansun synergisticantifungaleffectoffluconazolecombinedwithlicofeloneagainstresistantcandidaalbicans |