Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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Sirtinol Supresses Trophozoites Proliferation and Encystation of Acanthamoeba via Inhibition of Sirtuin Family Protein

  • Joo, So-Young (Department of Parasitology and Tropical Medicine, School of Medicine, Kyungpook National University) ;
  • Aung, Ja Moon (Department of Parasitology and Tropical Medicine, School of Medicine, Kyungpook National University) ;
  • Shin, Minsang (Department of Microbiology, School of Medicine, Kyungpook National University) ;
  • Moon, Eun-Kyung (Department of Medical Zoology, Kyung Hee University School of Medicine) ;
  • Kong, Hyun-Hee (Department of Parasitology, Dong-A University College of Medicine) ;
  • Goo, Youn-Kyoung (Department of Parasitology and Tropical Medicine, School of Medicine, Kyungpook National University) ;
  • Chung, Dong-Il (Department of Parasitology and Tropical Medicine, School of Medicine, Kyungpook National University) ;
  • Hong, Yeonchul (Department of Parasitology and Tropical Medicine, School of Medicine, Kyungpook National University)
  • Received : 2021.12.08
  • Accepted : 2022.01.27
  • Published : 2022.02.28
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Abstract

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.

Keywords

Acknowledgement

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (NRF-2019R1I1A1A01061647).

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