Bioactive compounds from Zanthoxylum acanthopodium phyllosphere bacteria with antifungal potential against Candida albicans

Main Article Content

ENNY NUGRAHENI
DEBIE RIZQOH
LIYA AGUSTIN UMAR
SIPRIYADI
AZELLA CHIKA FAUZIA
SHELLA SHARON

Abstract

Abstract. Nugraheni E, Rizqoh D, Umar LA, Sipriyadi, Fauzia AC, Sharon S. 2026. Bioactive compounds from Zanthoxylum acanthopodium phyllosphere bacteria with antifungal potential against Candida albicans. Biodiversitas 27 (1): d270102. https://doi.org/10.13057/biodiv/d270102. Zanthoxylum acanthopodium (andaliman), an endemic Rutaceae species from Samosir Island, Indonesia, with high economic and medicinal value, harbors phyllosphere bacteria that may produce antifungal metabolites. However, their bioactive compounds remain poorly characterized. This study aimed to identify bioactive compounds from the phyllosphere bacteria of Z. acanthopodium and to evaluate their antifungal potential against Candida albicans. Phyllosphere bacterial isolates were collected and evaluated against C. albicans grown in Potato Dextrose Broth (PDB) using a dilution assay to determine the minimum inhibitory concentration (MIC), and the ethyl acetate extracts were subsequently analyzed by GC-MS to identify constituent compounds. MIC assays showed that the crude extract inhibited C. albicans in all isolates at 100% concentration. Molecular identification based on 16S rRNA revealed these isolates as Brevundimonas sp. and Pseudomonas sp. GC-MS detected phenolic compounds, including isodiospyrin and 1-methyl-ethyl compound. Molecular docking using the C. albicans EXO-β-(1,3)-glucanase protein (PDB ID: 1EQP) demonstrated favorable binding energies (ΔG≤0), indicating spontaneous interactions. Isodiospyrin showed the strongest affinity with ΔG –8.56, while the 1-methyl-ethyl compound exhibited the best binding affinity and inhibition constant among the detected compounds. The findings confirm that phyllosphere bacteria of Z. acanthopodium exhibit antifungal activity against C. albicans. Isodiospyrin and 1-methyl-ethyl compound emerged as promising candidates for further antifungal development. Future studies should validate their efficacy through in vitro and in vivo assays, isolate specific antifungal metabolites, and optimize production for potential therapeutic applications.

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Author Biographies

DEBIE RIZQOH, Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, Universitas Bengkulu. Jl. WR. Supratman, Bengkulu 38371, Bengkulu, Indonesia

Microbiology Departement, Medical and Health Science Faculty

LIYA AGUSTIN UMAR, Department of Medical Biology, Faculty of Medical and Health Science, Universitas Bengkulu. Jl. WR. Supratman, Bengkulu 38371, Bengkulu, Indonesia

Biology Medical Departement

SIPRIYADI, Department of Microbiology, Faculty of Mathematics and Natural Sciences, Universitas Bengkulu. Jl. WR. Supratman, Bengkulu 38371, Bengkulu, Indonesia

Departement of Biology, Faculty of Mathematics and Natural Science 

References

Adrian, Syahputra RA, Juwita NA, Astyka R, Lubis MF. 2023. Andaliman (Zanthoxylum acanthopodium DC.) a herbal medicine from North Sumatera, Indonesia: Phytochemical and pharmacological review. Heliyon 9 (5): e16159. https://doi.org/10.1016/j.heliyon.2023.e16159.

Andrade-Pavón D, Gómez-García O, Villa-Tanaca L. 2024. Review and current perspectives on DNA topoisomerase I and II enzymes of fungi as study models for the development of new antifungal drugs. J Fungi 10 (9): 629. https://doi.org/10.3390/jof10090629.

Atriwal T, Azeem K, Husain FM, Hussain A, Khan MN, Alajmi MF, Abid M. 2021. Mechanistic understanding of Candida albicans biofilm formation and approaches for its inhibition. Front Microbiol 12: 638609. https://doi.org/10.3389/fmicb.2021.638609.

Awidya IGB, Rizqoh D, Lestari N, Sipriyadi S, Sariyanti M. 2024. Strong potential of white cambodia (Plumeria acuminata) phyllosphere bacteria which inhibit Candida albicans growth. Bio Web Conf 127: 05002. https://doi.org/10.1051/bioconf/202412705002.

Baukova A, Bogun A, Sushkova S, Minkina T, Mandzhieva S, Alliluev I, Jatav HS, Kalinitchenko V, Rajput VD, Delegan Y. 2024. New insights into Pseudomonas spp.-produced antibiotics: Genetic regulation of biosynthesis and implementation in biotechnology. Antibiotics 13 (7): 597. https://doi.org/10.3390/antibiotics13070597.

Bras G, Satala D, Juszczak M, Kulig K, Wronowska E, Bednarek A, Zawrotniak M, Rapala-Kozik M, Karkowska-Kuleta J. 2024. Secreted aspartic proteinases: Key factors in Candida infections and host-pathogen interactions. Intl J Mol Sci 25 (9): 4775. https://doi.org/10.3390/ijms25094775.

Brion LP, Uko SE, Goldman DL. 2007. Risk of resistance associated with fluconazole prophylaxis: Systematic review. J Infect 54 (6): 521-529. https://doi.org/10.1016/j.jinf.2006.11.017.

Fadlan A, Warsito T, Sarmoko S. 2021. Pendekatan in silico dalam menyikapi potensi antikanker meciadanol. Jurnal Kimia Riset 6 (2): 163-171. https://doi.org/10.20473/jkr.v6i2.31071. [Indonesian]

Hasibuan PAZ, Harahap U, Sitorus P, Lubis MF, Satria D. 2021. In-silico analysis of vernonioside d and vernonioside e from Vernonia amygdalina Delile. leaves as inhibitor of Epidermal Growth Factor Receptor (EGFR) and mammalian Target of Rapamycin (mTOR). Rasayan J Chem 14 (3): 1539-1543. https://doi.org/10.31788/rjc.2021.1436092.

Huang J, Zaynab M, Sharif Y, Khan J, Al-Yahyai R, Sadder M, Ali M, Alarab SR, Li S. 2024. Tannins as antimicrobial agents: Understanding toxic effects on pathogens. Toxicon 247: 107812. https://doi.org/10.1016/j.toxicon.2024.107812.

Hutapea DB, Susilawati Y, Muhaimin M, Chaerunisaa AY. 2024. Potent bioactivity of andaliman (Zanthoxylum acanthopodium DC.). Pharmacia 71: 1-10. https://doi.org/10.3897/pharmacia.71.e117812.

Jawhara S. 2022. How gut bacterial dysbiosis can promote Candida albicans overgrowth during colonic inflammation. Microorganisms 10 (5): 1014. https://doi.org/10.3390/microorganisms10051014.

Johnston-Monje D, Raizada MN. 2021. Conservation and diversity of seed associated endophytes in Zea across boundaries of evolution, ethnography and ecology. PLoS One 6 (6): e20396. https://doi.org/10.1371/journal.pone.0020396.

Katiyar C, Gupta A, Kanjilal S, Katiyar S. 2012. Drug discovery from plant sources: An integrated approach. AYU 33 (1): 10-19. https://doi.org/10.4103/0974-8520.100295

Kintamani E, Batubara I, Kusmana C, Tiryana T, Mirmanto E, Asoka SF. 2023. Essential oil compounds of andaliman (Zanthoxylum acanthopodium DC.) fruit varieties and their utilization as skin anti-aging using molecular docking. Life 13 (3): 754. https://doi.org/10.3390/life13030754.

Logan A, Wolfe A, Williamson JC. 2022. Antifungal resistance and the role of new therapeutic agents. Curr Infect Dis Rep 24 (9): 105-116. https://doi.org/10.1007/s11908-022-00782-5.

Lubis MF, Kaban VE, Aritonang JO, Satria D, Mulina AA, Febriani H. 2022. Acute toxicity and antifungal activity of the ointment Murraya koenigii ethanol extract. Rasayan J Chem 15 (1): 256-261. https://doi.org/10.31788/rjc.2022.1516401.

Meylani V, Rizal Putra R, Miftahussurur M, Sukardiman S, Eko Hermanto F, Abdullah A. 2023. Molecular docking analysis of Cinnamomum zeylanicum phytochemicals against secreted aspartyl proteinase 4-6 of Candida albicans as anti-candidiasis oral. Results Chem 5: 100721. https://doi.org/10.1016/j.rechem.2022.100721.

Nahar D, Mohite P, Lonkar A, Chidrawar VR, Dodiya R, Uddin MJ, Singh S, Prajapati BG. 2024. An insight into new strategies and targets to combat antifungal resistance: A comprehensive review. Eur J Med Chem Rep 10: 100120. https://doi.org/10.1016/j.ejmcr.2023.100120.

Nikalje AP, Ramesh G. 2018. Liquid chromatography-mass spectrometry and its applications: A brief review. Arch Org Inorg Chem Sci 1 (1): 26-34. https://doi.org/10.32474/aoics.2018.01.000103.

Nurlaeni Y, Junaedi DI, Iskandar J. 2024. Botany, morphology, ecology, cultivation, traditional utilization and conservation of andaliman (Zanthoxylum acanthopodium) in North Sumatra, Indonesia. Nusantara Bioscience 16 (1): 68-80. https://doi.org/10.13057/nusbiosci/n160109.

Pelczar MJ, Chan ECS Jr. 2008. Dasar-Dasar Mikrobiologi. Universitas Indonesia Press, Jakarta. [Indonesian]

Pinzi L, Rastelli G. 2019. Molecular docking: Shifting paradigms in drug discovery. Intl J Mol Sci 20 (18): 4331. https://doi.org/10.3390/ijms20184331.

Pratama MRF, Poerwono H, Siswodihardjo S. 2021. Introducing a two-dimensional graph of docking score difference vs. similarity of ligand-receptor interactions. Indonesian J Biotechnol 26: 54-60. https://doi.org/10.22146/ijbiotech.62194.

Prieto-Martínez FD, Arciniega M, Medina-Franco JL. 2018. Molecular docking: Current advances and challenges. TIP Revista Especializada En Ciencias Químico-Biológicas 21: 65-87. https://doi.org/10.22201/fesz.23958723e.2018.0.143.

Rajamanickam K, Sudha SS, Francis M, Sowmya T, Rengaramanujam J, Sivalingam P, Prabakar K. 2013. Microalgae associated Brevundimonas sp. MSK 4 as the nano particle synthesizing unit to produce antimicrobial silver nanoparticles. Spectrochim Acta A Mol Biomol Spectrosc 113: 10-14. https://doi.org/10.1016/j.saa.2013.04.083.

Rizqoh D, Sipriyadi, Mas’ud N, Rahmawati ID, Sharon S, Suryani UH, Lestari N, Oktoviani, Wibowo RH. 2024a. Phyllosphere bacteria of andaliman (Zanctoxylum acanthopodium DC.) as potential antimicrobial compounds source against pathogenic bacteria. Front Health Inform 13 (3): 6399-6408.

Rizqoh D, Sipriyadi, Suryani UH, Putri CN, Agustin M, Taurustya H, Lestari N, Sariyanti M. 2024b. Exploring the antibacterial activity of endophytic bacteria from andaliman (Zanthoxylum acanthopodium) against Bacillus subtilis. Biodiversitas 25 (2): 700-707. https://doi.org/10.13057/biodiv/d250229.

Rizqoh D, Yolanda SD, Nugraheni E, Sipriyadi, Uliyandaria M, Wibowo RH, Oktoviani, Djatmiko EM, Putri AA. 2025. Antibacterial activity of phyllospheric bacteria isolated from Rhizophora mucronata against Escherichia coli and Bacillus subtilis. Biodiversitas 26 (1): 199-210. https://doi.org/10.13057/biodiv/d260121.

Shaker B, Ahmad S, Lee J, Jung C, Na D. 2021. In silico methods and tools for drug discovery. Comput Biol Med 137: 104851. https://doi.org/10.1016/j.compbiomed.2021.104851.

Soeka YS, Naiola E, Sulistyo J. 2007. Aktivitas antimikroba flavonoid - glikosida hasil sintesis secara transglikosilasi enzimatik. Berita Biologi 8: 455-464. [Indonesian]

Steven B, Huntley RB, Zeng Q. 2018. The influence of flower anatomy and apple cultivar on the apple flower phytobiome. Phytobiomes J 2 (3): 171-179. https://doi.org/10.1094/pbiomes-03-18-0015-r.

Ting C-Y, Hsu C-T, Hsu H-T, Su J-S, Chen T-Y, Tarn W-Y, Kuo Y-H, Whang-Peng J, Liu LF, Hwang J. 2003. Isodiospyrin as a novel human DNA topoisomerase I inhibitor. Biochem Pharmacol 66 (10): 1981-1991. https://doi.org/10.1016/j.bcp.2003.07.003.

Vetvicka V, Teplyakova TV, Shintyapina AB, Korolenko TA. 2021. Effects of medicinal fungi-derived β-glucan on tumor progression. J Fungi 7 (4): 250. https://doi.org/10.3390/jof7040250.

Wagner AS, Lumsdaine SW, Mangrum MM, Reynolds TB. 2023. Caspofungin-induced β(1,3)-glucan exposure in Candida albicans is driven by increased chitin levels. mBio 14 (4): e0007423. https://doi.org/10.1128/mbio.00074-23.

Wiederhold NP. 2017. Antifungal resistance: Current trends and future strategies to combat. Infect Drug Resist 10: 249-259. https://doi.org/10.2147/idr.s124918.

Yu Z, Wu X, He J. 2022. Study on the antifungal activity and mechanism of tea saponin from Camellia oleifera cake. Eur Food Res Technol 248: 783-795. https://doi.org/10.1007/s00217-021-03929-1.

Zhang B, Li H, Yu K, Jin Z. 2022. Molecular docking-based computational platform for high-throughput virtual screening. CCF Trans High Perform Comput 4 (1): 63-74. https://doi.org/10.1007/s42514-021-00086-5.

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