Analysis of the role of acetylation in Giardia lamblia and the giardicidal potential of garcinol
IntroductionPost-translational modifications of proteins provide cellular physiology with a broad range of adaptability to the external environment flexibly and rapidly. In the case of the protozoan parasite Giardia lamblia, the study of these modifications has gained relevance in recent years, main...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Microbiology |
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| author | Rocío G. Patolsky Jerónimo Laiolo Jerónimo Laiolo Luciano Díaz-Pérez Gabriel Luna Pizarro Gonzalo F. Mayol María C. Touz Constanza Feliziani Andrea S. Rópolo |
| author_facet | Rocío G. Patolsky Jerónimo Laiolo Jerónimo Laiolo Luciano Díaz-Pérez Gabriel Luna Pizarro Gonzalo F. Mayol María C. Touz Constanza Feliziani Andrea S. Rópolo |
| author_sort | Rocío G. Patolsky |
| collection | DOAJ |
| description | IntroductionPost-translational modifications of proteins provide cellular physiology with a broad range of adaptability to the external environment flexibly and rapidly. In the case of the protozoan parasite Giardia lamblia, the study of these modifications has gained relevance in recent years, mainly focusing on methylation and deacetylation of proteins. This study investigates the significance of acetylation in this protozoan parasite.MethodsThis study explores the role of acetylation in G. lamblia through a combination of immunofluorescence assays, manipulation of acetyltransferase enzymes, and the use of garcinol, an acetylation inhibitor, during the growth phase.ResultsThe acetylation of histone marks H3K9 and H3K27 occurs during growth and is followed by deacetylation during encystation. Transfections modifying acetyltransferase activity induced a latent cellular state, underscoring the importance of protein acetylation for parasite survival. Garcinol treatment during growth caused significant morphological changes, including plasma membrane blebbing and apoptotic-like bodies. Immunofluorescence revealed these bodies contained α-tubulin/acetylated α-tubulin and reactive oxygen species. Flow cytometry and Annexin V staining indicated early apoptosis within 24 hours of treatment. Additionally, garcinol led to the deacetylation of H3K9 and H3K27, with redistribution of tubulin and acetylated tubulin from microtubules to the cytosol. Significantly, garcinol prevented parasite recrudescence after treatment withdrawal.DiscussionThese results demonstrate that acetylation is essential for trophozoite survival and highlight the natural histone acetyltransferase inhibitor garcinol as a potential candidate for drug development against giardiasis, considering its giardicidal activity. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj-art-4017d9684efb4400a71b3d02b22fa35c2025-01-03T05:10:17ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-01-011510.3389/fmicb.2024.15130531513053Analysis of the role of acetylation in Giardia lamblia and the giardicidal potential of garcinolRocío G. Patolsky0Jerónimo Laiolo1Jerónimo Laiolo2Luciano Díaz-Pérez3Gabriel Luna Pizarro4Gonzalo F. Mayol5María C. Touz6Constanza Feliziani7Andrea S. Rópolo8Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba, Córdoba, ArgentinaInstituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba, Córdoba, ArgentinaUniversidad Católica de Córdoba, Córdoba, ArgentinaInstituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba, Córdoba, ArgentinaInstituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba, Córdoba, ArgentinaInstituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba, Córdoba, ArgentinaInstituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba, Córdoba, ArgentinaInstituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba, Córdoba, ArgentinaInstituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Córdoba, Córdoba, ArgentinaIntroductionPost-translational modifications of proteins provide cellular physiology with a broad range of adaptability to the external environment flexibly and rapidly. In the case of the protozoan parasite Giardia lamblia, the study of these modifications has gained relevance in recent years, mainly focusing on methylation and deacetylation of proteins. This study investigates the significance of acetylation in this protozoan parasite.MethodsThis study explores the role of acetylation in G. lamblia through a combination of immunofluorescence assays, manipulation of acetyltransferase enzymes, and the use of garcinol, an acetylation inhibitor, during the growth phase.ResultsThe acetylation of histone marks H3K9 and H3K27 occurs during growth and is followed by deacetylation during encystation. Transfections modifying acetyltransferase activity induced a latent cellular state, underscoring the importance of protein acetylation for parasite survival. Garcinol treatment during growth caused significant morphological changes, including plasma membrane blebbing and apoptotic-like bodies. Immunofluorescence revealed these bodies contained α-tubulin/acetylated α-tubulin and reactive oxygen species. Flow cytometry and Annexin V staining indicated early apoptosis within 24 hours of treatment. Additionally, garcinol led to the deacetylation of H3K9 and H3K27, with redistribution of tubulin and acetylated tubulin from microtubules to the cytosol. Significantly, garcinol prevented parasite recrudescence after treatment withdrawal.DiscussionThese results demonstrate that acetylation is essential for trophozoite survival and highlight the natural histone acetyltransferase inhibitor garcinol as a potential candidate for drug development against giardiasis, considering its giardicidal activity.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1513053/fullacetylationparasitesantigiardial drugslysine acetyltransferasesgarcinol |
| spellingShingle | Rocío G. Patolsky Jerónimo Laiolo Jerónimo Laiolo Luciano Díaz-Pérez Gabriel Luna Pizarro Gonzalo F. Mayol María C. Touz Constanza Feliziani Andrea S. Rópolo Analysis of the role of acetylation in Giardia lamblia and the giardicidal potential of garcinol Frontiers in Microbiology acetylation parasites antigiardial drugs lysine acetyltransferases garcinol |
| title | Analysis of the role of acetylation in Giardia lamblia and the giardicidal potential of garcinol |
| title_full | Analysis of the role of acetylation in Giardia lamblia and the giardicidal potential of garcinol |
| title_fullStr | Analysis of the role of acetylation in Giardia lamblia and the giardicidal potential of garcinol |
| title_full_unstemmed | Analysis of the role of acetylation in Giardia lamblia and the giardicidal potential of garcinol |
| title_short | Analysis of the role of acetylation in Giardia lamblia and the giardicidal potential of garcinol |
| title_sort | analysis of the role of acetylation in giardia lamblia and the giardicidal potential of garcinol |
| topic | acetylation parasites antigiardial drugs lysine acetyltransferases garcinol |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1513053/full |
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