The histone methyltransferase DOT1B is dispensable for stage differentiation and macrophage infection of Leishmania mexicana

Conserved histone methyltransferases of the DOT1 family are involved in replication regulation, cell cycle progression, stage differentiation, and gene regulation in trypanosomatids. However, the specific functions of these enzymes depend on the host evasion strategies of the parasites. In this stud...

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Main Authors: Nicole Eisenhuth, Elisa Theres Rauh, Melina Mitnacht, Andrea Debus, Ulrike Schleicher, Falk Butter, Katerina Pruzinova, Petr Volf, Christian J. Janzen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2024.1502339/full
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author Nicole Eisenhuth
Elisa Theres Rauh
Melina Mitnacht
Andrea Debus
Ulrike Schleicher
Falk Butter
Katerina Pruzinova
Petr Volf
Christian J. Janzen
author_facet Nicole Eisenhuth
Elisa Theres Rauh
Melina Mitnacht
Andrea Debus
Ulrike Schleicher
Falk Butter
Katerina Pruzinova
Petr Volf
Christian J. Janzen
author_sort Nicole Eisenhuth
collection DOAJ
description Conserved histone methyltransferases of the DOT1 family are involved in replication regulation, cell cycle progression, stage differentiation, and gene regulation in trypanosomatids. However, the specific functions of these enzymes depend on the host evasion strategies of the parasites. In this study, we investigated the role of DOT1B in Leishmania mexicana, focusing on life cycle progression and infectivity. In contrast to Trypanosoma brucei, in which DOT1B is essential for the differentiation of mammal-infective bloodstream forms to insect procyclic forms, L. mexicana DOT1B (LmxDOT1B) is not critical for the differentiation of promastigotes to amastigotes in vitro. Additionally, there are no significant differences in the ability to infect or differentiate in macrophages or sand fly vectors between the LmxDOT1B-depleted and control strains. These findings highlight the divergence of the function of DOT1B in these related parasites, suggesting genus-specific adaptations in the use of histone modifications for life cycle progression and host adaptation processes.
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spelling doaj-art-fc56401b15684082a3feeec78859b9f82025-01-20T05:23:49ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-01-011410.3389/fcimb.2024.15023391502339The histone methyltransferase DOT1B is dispensable for stage differentiation and macrophage infection of Leishmania mexicanaNicole Eisenhuth0Elisa Theres Rauh1Melina Mitnacht2Andrea Debus3Ulrike Schleicher4Falk Butter5Katerina Pruzinova6Petr Volf7Christian J. Janzen8Department of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, GermanyDepartment of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, GermanyDepartment of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, GermanyMicrobiology Institute-Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander-University, Erlangen, GermanyMicrobiology Institute-Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander-University, Erlangen, GermanyProteomics und Systems Biology, Institute of Molecular Virology and Cell Biology (IMVZ), Friedrich Loeffler Institute, Greifswald, GermanyDepartment of Parasitology, Charles University, Prague, CzechiaDepartment of Parasitology, Charles University, Prague, CzechiaDepartment of Cell and Developmental Biology, Biocenter, University of Würzburg, Würzburg, GermanyConserved histone methyltransferases of the DOT1 family are involved in replication regulation, cell cycle progression, stage differentiation, and gene regulation in trypanosomatids. However, the specific functions of these enzymes depend on the host evasion strategies of the parasites. In this study, we investigated the role of DOT1B in Leishmania mexicana, focusing on life cycle progression and infectivity. In contrast to Trypanosoma brucei, in which DOT1B is essential for the differentiation of mammal-infective bloodstream forms to insect procyclic forms, L. mexicana DOT1B (LmxDOT1B) is not critical for the differentiation of promastigotes to amastigotes in vitro. Additionally, there are no significant differences in the ability to infect or differentiate in macrophages or sand fly vectors between the LmxDOT1B-depleted and control strains. These findings highlight the divergence of the function of DOT1B in these related parasites, suggesting genus-specific adaptations in the use of histone modifications for life cycle progression and host adaptation processes.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1502339/fullhistone methyltransferaseDOT1Leishmania mexicanavirulencedifferentiationsand fly
spellingShingle Nicole Eisenhuth
Elisa Theres Rauh
Melina Mitnacht
Andrea Debus
Ulrike Schleicher
Falk Butter
Katerina Pruzinova
Petr Volf
Christian J. Janzen
The histone methyltransferase DOT1B is dispensable for stage differentiation and macrophage infection of Leishmania mexicana
Frontiers in Cellular and Infection Microbiology
histone methyltransferase
DOT1
Leishmania mexicana
virulence
differentiation
sand fly
title The histone methyltransferase DOT1B is dispensable for stage differentiation and macrophage infection of Leishmania mexicana
title_full The histone methyltransferase DOT1B is dispensable for stage differentiation and macrophage infection of Leishmania mexicana
title_fullStr The histone methyltransferase DOT1B is dispensable for stage differentiation and macrophage infection of Leishmania mexicana
title_full_unstemmed The histone methyltransferase DOT1B is dispensable for stage differentiation and macrophage infection of Leishmania mexicana
title_short The histone methyltransferase DOT1B is dispensable for stage differentiation and macrophage infection of Leishmania mexicana
title_sort histone methyltransferase dot1b is dispensable for stage differentiation and macrophage infection of leishmania mexicana
topic histone methyltransferase
DOT1
Leishmania mexicana
virulence
differentiation
sand fly
url https://www.frontiersin.org/articles/10.3389/fcimb.2024.1502339/full
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