The encystation of Acanthamoeba leads to the development of metabolically inactive and dormant cysts from vegetative trophozoites under unfavorable conditions. These cysts are highly resistant to anti-Acanthamoeba drugs and biocides. Therefore, the inhibition of encystation would be more effective in treating Acanthamoeba infection. In our previous study, a sirtuin family protein—Acanthamoeba silent-information regulator 2-like protein (AcSir2)—was identified, and its expression was discovered to be critical for Acanthamoeba castellanii proliferation and encystation. In this study, to develop Acanthamoeba sirtuin inhibitors, we examine the effects of sirtinol, a sirtuin inhibitor, on trophozoite growth and encystation. Sirtinol inhibited A. castellanii trophozoites proliferation (IC50=61.24 μM). The encystation rate of cells treated with sirtinol significantly decreased to 39.8% (200 μM sirtinol) after 24 hr of incubation compared to controls. In AcSir2-overexpressing cells, the transcriptional level of cyst-specific cysteine protease (CSCP), an Acanthamoeba cysteine protease involved in the encysting process, was 11.6- and 88.6-fold higher at 48 and 72 hr after induction of encystation compared to control. However, sirtinol suppresses CSCP transcription, resulting that the undegraded organelles and large molecules remained in sirtinol-treated cells during encystation. These results indicated that sirtinol sufficiently inhibited trophozoite proliferation and encystation, and can be used to treat Acanthamoeba infections.
Citations
Citations to this article as recorded by
Pterostilbene: A natural neuroprotective stilbene with anti-Alzheimer's disease properties Songlan Gao, Honglei Zhang, Na Li, Lijuan Zhang, Zhe Zhu, Changlu Xu Journal of Pharmaceutical Analysis.2025; 15(4): 101043. CrossRef
Alzheimer’s Disease: A Review of Molecular Mechanisms and Therapeutic Implications by Targeting Sirtuins, Caspases, and GSK-3 Kalpana Pandya, Krishnashish Roul, Avanish Tripathi, Sateesh Belemkar, Anshuman Sinha, Meryem Erol, Devendra Kumar ACS Chemical Neuroscience.2025; 16(12): 2178. CrossRef
Human Conjunctival Transcriptome in Acanthamoeba Keratitis: An Exploratory Study Gerami D. Seitzman, Jeremy D. Keenan, Thomas M. Lietman, Kevin Ruder, Lina Zhong, Cindi Chen, YuHeng Liu, Danny Yu, Thomas Abraham, Armin Hinterwirth, Thuy Doan Cornea.2024; 43(10): 1272. CrossRef
Comparative cytotoxicity of Acanthamoeba castellanii-derived conditioned medium on human corneal epithelial and stromal cells Abdullah Alhazmi, Laura E. Sidney, Andy Hopkinson, Hany M. Elsheikha Acta Tropica.2024; 257: 107288. CrossRef
Biological characteristics and pathogenicity of Acanthamoeba Yuehua Wang, Linzhe Jiang, Yitong Zhao, Xiaohong Ju, Le Wang, Liang Jin, Ryan D. Fine, Mingguang Li Frontiers in Microbiology.2023;[Epub] CrossRef
Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human popu- lation worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effec- tive drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4- HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with T. gondii and the proliferation of T. gondii in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expres- sion of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1- mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.
Citations
Citations to this article as recorded by
Impact of prenatal phthalate exposure on newborn metabolome and infant neurodevelopment Susan S. Hoffman, Ziyin Tang, Anne Dunlop, Patricia A. Brennan, Thompson Huynh, Stephanie M. Eick, Dana B. Barr, Blake Rushing, Susan L. McRitchie, Susan Sumner, Kaitlin R. Taibl, Youran Tan, Parinya Panuwet, Grace E. Lee, Jasmin Eatman, Elizabeth J. Corw Nature Communications.2025;[Epub] CrossRef
Neospora caninum
infection specifically suppresses the expression of a host lncRNA
XR_001919077.1
to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy
Shan-Shan Zhao, De-Liang Tao, Jin-Ming Chen, Ming-Yi Zhang, Xin Yang, Jun-Ke Song, Qun Liu, Guang-Hui Zhao, Björn F. C. Kafsack Microbiology Spectrum.2025;[Epub] CrossRef
Synthesis, structural characterization, in silico ADMET and molecular docking studies of a Schiff base derived from 4-hydroxybenzaldehyde and 4-aminobenzoic acid Patryk Nowak, Artur Sikorski New Journal of Chemistry.2025; 49(14): 5940. CrossRef
Metabolomic Plasma Profile of Chronic Obstructive Pulmonary Disease Patients Carme Casadevall, Bella Agranovich, Cesar Jesse Enríquez-Rodríguez, Rosa Faner, Sergi Pascual-Guàrdia, Ady Castro-Acosta, Ramon Camps-Ubach, Judith Garcia-Aymerich, Esther Barreiro, Eduard Monsó, Luis Seijo, Juan José Soler-Cataluña, Salud Santos, Germán International Journal of Molecular Sciences.2025; 26(10): 4526. CrossRef
The role of host autophagy in intracellular protozoan parasites diseases Rafael Cardoso Maciel Costa Silva, Jhones Sousa Ribeiro, Thalita Santos de Moraes de Farias, Leonardo Holanda Travassos Archives of Biochemistry and Biophysics.2024; 761: 110186. CrossRef
Structural diversity of cocrystals formed from acridine and two isomers of hydroxybenzaldehyde: 3-hydroxybenzaldehyde and 4-hydroxybenzaldehyde Patryk Nowak, Artur Sikorski RSC Advances.2023; 13(29): 20105. CrossRef
Protective effect of benzaldehyde combined with albendazole against brain injury induced by Angiostrongylus cantonensis infection in mice Kuang-Yao Chen, Chien-Ju Cheng, Yi-Ju Chen, Cheng-Hsun Chiu, Lian-Chen Wang International Journal of Antimicrobial Agents.2023; 62(5): 106963. CrossRef
Benzaldehyde Attenuates the Fifth Stage Larval Excretory–Secretory Product of Angiostrongylus cantonensis-Induced Injury in Mouse Astrocytes via Regulation of Endoplasmic Reticulum Stress and Oxidative Stress Kuang-Yao Chen, Yi-Ju Chen, Chien-Ju Cheng, Kai-Yuan Jhan, Lian-Chen Wang Biomolecules.2022; 12(2): 177. CrossRef
Modulation of autophagy as a therapeutic strategy for Toxoplasma gondii infection Ao Cheng, Huanan Zhang, Baike Chen, Shengyao Zheng, Hongyi Wang, Yijia Shi, Siyao You, Ming Li, Liping Jiang Frontiers in Cellular and Infection Microbiology.2022;[Epub] CrossRef
SIRT1 Promotes Host Protective Immunity against Toxoplasma gondii by Controlling the FoxO-Autophagy Axis via the AMPK and PI3K/AKT Signalling Pathways Jina Lee, Jinju Kim, Jae-Hyung Lee, Yong Min Choi, Hyeonil Choi, Hwan-Doo Cho, Guang-Ho Cha, Young-Ha Lee, Eun-Kyeong Jo, Byung-Hyun Park, Jae-Min Yuk International Journal of Molecular Sciences.2022; 23(21): 13578. CrossRef
The role of SIRT1 in the process of Toxoplasma gondii infection of RAW 264.7 macrophages Kai Dong, Ziyang Jiang, Jianhui Zhang, Hanxiao Qin, Jianping Chen, Qiwei Chen Frontiers in Microbiology.2022;[Epub] CrossRef
Recent Advances in the Roles of Autophagy and Autophagy Proteins in Host Cells During Toxoplasma gondii Infection and Potential Therapeutic Implications Carlos S. Subauste Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
Analysis of Phenolic Compounds in Coix-seed Reactive Derivatives(CRD) by Using Liquid Chromatography/Mass Spectrometry(LC-MS) Nobutaka SUZUKI, Masahiko TAKINO, Hirotaka OKUWA-HAYASHI Japanese Journal of Complementary and Alternative Medicine.2020; 17(1): 11. CrossRef
Urolithin-A attenuates neurotoxoplasmosis and alters innate response towards predator odor Sijie Tan, Wen Han Tong, Ajai Vyas Brain, Behavior, & Immunity - Health.2020; 8: 100128. CrossRef
The Host Autophagy During Toxoplasma Infection Minmin Wu, Obed Cudjoe, Jilong Shen, Ying Chen, Jian Du Frontiers in Microbiology.2020;[Epub] CrossRef
First
Prev
