A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function
Global burden of fungal infections and related health risk has accelerated at an incredible pace, and multidrug resistance emergency aggravates the need for the development of new effective strategies. Candida albicans is clinically the most ubiquitous pathogenic fungus that leads to high incidence...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.872322/full |
| _version_ | 1811332221984833536 |
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| author | Chao-Qin Sun Chao-Qin Sun Jian Peng Jian Peng Long-Bing Yang Zheng-Long Jiao Zheng-Long Jiao Luo-Xiong Zhou Luo-Xiong Zhou Ru-Yu Tao Li-Juan Zhu Zhu-Qing Tian Ming-Jiao Huang Guo Guo Guo Guo Guo Guo |
| author_facet | Chao-Qin Sun Chao-Qin Sun Jian Peng Jian Peng Long-Bing Yang Zheng-Long Jiao Zheng-Long Jiao Luo-Xiong Zhou Luo-Xiong Zhou Ru-Yu Tao Li-Juan Zhu Zhu-Qing Tian Ming-Jiao Huang Guo Guo Guo Guo Guo Guo |
| author_sort | Chao-Qin Sun |
| collection | DOAJ |
| description | Global burden of fungal infections and related health risk has accelerated at an incredible pace, and multidrug resistance emergency aggravates the need for the development of new effective strategies. Candida albicans is clinically the most ubiquitous pathogenic fungus that leads to high incidence and mortality in immunocompromised patients. Antimicrobial peptides (AMPs), in this context, represent promising alternatives having potential to be exploited for improving human health. In our previous studies, a Cecropin-4-derived peptide named C18 was found to possess a broader antibacterial spectrum after modification and exhibit significant antifungal activity against C. albicans. In this study, C18 shows antifungal activity against C. albicans or non-albicans Candida species with a minimum inhibitory concentration (MIC) at 4∼32 μg/ml, and clinical isolates of fluconazole (FLZ)-resistance C. tropicalis were highly susceptible to C18 with MIC value of 8 or 16 μg/ml. Additionally, C18 is superior to FLZ for killing planktonic C. albicans from inhibitory and killing kinetic curves. Moreover, C18 could attenuate the virulence of C. albicans, which includes damaging the cell structure, retarding hyphae transition, and inhibiting biofilm formation. Intriguingly, in the Galleria mellonella model with C. albicans infection, C18 could improve the survival rate of G. mellonella larvae to 70% and reduce C. albicans load from 5.01 × 107 to 5.62 × 104 CFU. For mechanistic action of C18, the level of reactive oxygen species (ROS) generation and cytosolic Ca2 + increased in the presence of C18, which is closely associated with mitochondrial dysfunction. Meanwhile, mitochondrial membrane potential (△Ψm) loss and ATP depletion of C. albicans occurred with the treatment of C18. We hypothesized that C18 might inhibit C. albicans via triggering mitochondrial dysfunction driven by ROS generation and Ca2 + accumulation. Our observation provides a basis for future research to explore the antifungal strategies and presents C18 as an attractive therapeutic candidate to be developed to treat candidiasis. |
| first_indexed | 2024-04-13T16:33:41Z |
| format | Article |
| id | doaj.art-bee10905259a46baa10d6d30eef2871d |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T16:33:41Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-bee10905259a46baa10d6d30eef2871d2022-12-22T02:39:30ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-04-011310.3389/fmicb.2022.872322872322A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial FunctionChao-Qin Sun0Chao-Qin Sun1Jian Peng2Jian Peng3Long-Bing Yang4Zheng-Long Jiao5Zheng-Long Jiao6Luo-Xiong Zhou7Luo-Xiong Zhou8Ru-Yu Tao9Li-Juan Zhu10Zhu-Qing Tian11Ming-Jiao Huang12Guo Guo13Guo Guo14Guo Guo15The Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaCenter of Laboratory Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaThe Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaKey Laboratory of Environmental Pollution Monitoring and Disease Control, Guizhou Medical University, Ministry of Education, Guiyang, ChinaThe Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaThe Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaTranslational Medicine Research Center, Guizhou Medical University, Guiyang, ChinaThe Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaKey Laboratory of Environmental Pollution Monitoring and Disease Control, Guizhou Medical University, Ministry of Education, Guiyang, ChinaDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guizhou Medical University, Kaili, ChinaThe Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaThe Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaThe Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaThe Key and Characteristic Laboratory of Modern Pathogen Biology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaKey Laboratory of Environmental Pollution Monitoring and Disease Control, Guizhou Medical University, Ministry of Education, Guiyang, ChinaTranslational Medicine Research Center, Guizhou Medical University, Guiyang, ChinaGlobal burden of fungal infections and related health risk has accelerated at an incredible pace, and multidrug resistance emergency aggravates the need for the development of new effective strategies. Candida albicans is clinically the most ubiquitous pathogenic fungus that leads to high incidence and mortality in immunocompromised patients. Antimicrobial peptides (AMPs), in this context, represent promising alternatives having potential to be exploited for improving human health. In our previous studies, a Cecropin-4-derived peptide named C18 was found to possess a broader antibacterial spectrum after modification and exhibit significant antifungal activity against C. albicans. In this study, C18 shows antifungal activity against C. albicans or non-albicans Candida species with a minimum inhibitory concentration (MIC) at 4∼32 μg/ml, and clinical isolates of fluconazole (FLZ)-resistance C. tropicalis were highly susceptible to C18 with MIC value of 8 or 16 μg/ml. Additionally, C18 is superior to FLZ for killing planktonic C. albicans from inhibitory and killing kinetic curves. Moreover, C18 could attenuate the virulence of C. albicans, which includes damaging the cell structure, retarding hyphae transition, and inhibiting biofilm formation. Intriguingly, in the Galleria mellonella model with C. albicans infection, C18 could improve the survival rate of G. mellonella larvae to 70% and reduce C. albicans load from 5.01 × 107 to 5.62 × 104 CFU. For mechanistic action of C18, the level of reactive oxygen species (ROS) generation and cytosolic Ca2 + increased in the presence of C18, which is closely associated with mitochondrial dysfunction. Meanwhile, mitochondrial membrane potential (△Ψm) loss and ATP depletion of C. albicans occurred with the treatment of C18. We hypothesized that C18 might inhibit C. albicans via triggering mitochondrial dysfunction driven by ROS generation and Ca2 + accumulation. Our observation provides a basis for future research to explore the antifungal strategies and presents C18 as an attractive therapeutic candidate to be developed to treat candidiasis.https://www.frontiersin.org/articles/10.3389/fmicb.2022.872322/fullcecropin-4 derived peptideCandida albicansROSmitochondrial dysfunctionG. mellonellaantifungal activity |
| spellingShingle | Chao-Qin Sun Chao-Qin Sun Jian Peng Jian Peng Long-Bing Yang Zheng-Long Jiao Zheng-Long Jiao Luo-Xiong Zhou Luo-Xiong Zhou Ru-Yu Tao Li-Juan Zhu Zhu-Qing Tian Ming-Jiao Huang Guo Guo Guo Guo Guo Guo A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function Frontiers in Microbiology cecropin-4 derived peptide Candida albicans ROS mitochondrial dysfunction G. mellonella antifungal activity |
| title | A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function |
| title_full | A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function |
| title_fullStr | A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function |
| title_full_unstemmed | A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function |
| title_short | A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function |
| title_sort | cecropin 4 derived peptide c18 inhibits candida albicans by disturbing mitochondrial function |
| topic | cecropin-4 derived peptide Candida albicans ROS mitochondrial dysfunction G. mellonella antifungal activity |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.872322/full |
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