The Transcriptome of <italic toggle="yes">Leishmania major</italic> Developmental Stages in Their Natural Sand Fly Vector

ABSTRACT The life cycle of the Leishmania parasite in the sand fly vector involves differentiation into several distinctive forms, each thought to represent an adaptation to specific microenvironments in the midgut of the fly. Based on transcriptome sequencing (RNA-Seq) results, we describe the firs...

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Autores principales:	Ehud Inbar, V. Keith Hughitt, Laura A. L. Dillon, Kashinath Ghosh, Najib M. El-Sayed, David L. Sacks
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Leishmania sand fly transcriptome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0237bcd8c10b4444ae0c597be089eebf
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spelling	oai:doaj.org-article:0237bcd8c10b4444ae0c597be089eebf2021-11-15T15:51:00ZThe Transcriptome of <italic toggle="yes">Leishmania major</italic> Developmental Stages in Their Natural Sand Fly Vector10.1128/mBio.00029-172150-7511https://doaj.org/article/0237bcd8c10b4444ae0c597be089eebf2017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00029-17https://doaj.org/toc/2150-7511ABSTRACT The life cycle of the Leishmania parasite in the sand fly vector involves differentiation into several distinctive forms, each thought to represent an adaptation to specific microenvironments in the midgut of the fly. Based on transcriptome sequencing (RNA-Seq) results, we describe the first high-resolution analysis of the transcriptome dynamics of four distinct stages of Leishmania major as they develop in a natural vector, Phlebotomus duboscqi. The early transformation from tissue amastigotes to procyclic promastigotes in the blood-fed midgut was accompanied by the greatest number of differentially expressed genes, including the downregulation of amastins, and upregulation of multiple cell surface proteins, sugar and amino acid transporters, and genes related to glucose metabolism and cell cycle progression. The global changes accompanying post-blood meal differentiation of procyclic promastigotes to the nectomonad and metacyclic stages were less extensive, though each displayed a unique signature. The transcriptome of nectomonads, which has not been studied previously, revealed changes consistent with cell cycle arrest and the upregulation of genes associated with starvation and stress, including autophagic pathways of protein recycling. Maturation to the infective, metacyclic stage was accompanied by changes suggesting preadaptation to the intracellular environment of the mammalian host, demonstrated by the amastigote-like profiles of surface proteins and metabolism-related genes. Finally, a direct comparison between sand fly-derived and culture-derived metacyclics revealed a reassuring similarity between the two forms, with the in vivo forms distinguished mainly by a stronger upregulation of transcripts associated with nutrient stress. IMPORTANCE The life cycle of Leishmania parasites in the sand fly vector includes their growth and development as morphologically distinct forms of extracellular promastigotes found within the different microenvironments of the gut. Based on RNA-Seq, we provide here the first high-resolution, transcriptomic analysis of Leishmania insect stages during their cyclical development in vivo, from tissue amastigotes ingested with the blood meal to infective, metacyclic promastigotes that initiate infection in the mammalian host. The most extensive genetic reprogramming occurred during the early transformation of amastigotes to rapidly dividing procyclic promastigotes in the blood-fed midgut, with major changes in the abundance of mRNAs for surface proteins and metabolism. The post-blood meal-adapted nectomonad stage was characterized by the downregulation of cell cycle-related genes and the upregulation of stress- and starvation-related genes. Finally, the transcriptome of metacyclic promastigotes shifted to a more amastigote-like profile, suggesting their preadaptation to the intracellular host environment.Ehud InbarV. Keith HughittLaura A. L. DillonKashinath GhoshNajib M. El-SayedDavid L. SacksAmerican Society for MicrobiologyarticleLeishmaniasand flytranscriptomeMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Leishmania sand fly transcriptome Microbiology QR1-502
spellingShingle	Leishmania sand fly transcriptome Microbiology QR1-502 Ehud Inbar V. Keith Hughitt Laura A. L. Dillon Kashinath Ghosh Najib M. El-Sayed David L. Sacks The Transcriptome of <italic toggle="yes">Leishmania major</italic> Developmental Stages in Their Natural Sand Fly Vector
description	ABSTRACT The life cycle of the Leishmania parasite in the sand fly vector involves differentiation into several distinctive forms, each thought to represent an adaptation to specific microenvironments in the midgut of the fly. Based on transcriptome sequencing (RNA-Seq) results, we describe the first high-resolution analysis of the transcriptome dynamics of four distinct stages of Leishmania major as they develop in a natural vector, Phlebotomus duboscqi. The early transformation from tissue amastigotes to procyclic promastigotes in the blood-fed midgut was accompanied by the greatest number of differentially expressed genes, including the downregulation of amastins, and upregulation of multiple cell surface proteins, sugar and amino acid transporters, and genes related to glucose metabolism and cell cycle progression. The global changes accompanying post-blood meal differentiation of procyclic promastigotes to the nectomonad and metacyclic stages were less extensive, though each displayed a unique signature. The transcriptome of nectomonads, which has not been studied previously, revealed changes consistent with cell cycle arrest and the upregulation of genes associated with starvation and stress, including autophagic pathways of protein recycling. Maturation to the infective, metacyclic stage was accompanied by changes suggesting preadaptation to the intracellular environment of the mammalian host, demonstrated by the amastigote-like profiles of surface proteins and metabolism-related genes. Finally, a direct comparison between sand fly-derived and culture-derived metacyclics revealed a reassuring similarity between the two forms, with the in vivo forms distinguished mainly by a stronger upregulation of transcripts associated with nutrient stress. IMPORTANCE The life cycle of Leishmania parasites in the sand fly vector includes their growth and development as morphologically distinct forms of extracellular promastigotes found within the different microenvironments of the gut. Based on RNA-Seq, we provide here the first high-resolution, transcriptomic analysis of Leishmania insect stages during their cyclical development in vivo, from tissue amastigotes ingested with the blood meal to infective, metacyclic promastigotes that initiate infection in the mammalian host. The most extensive genetic reprogramming occurred during the early transformation of amastigotes to rapidly dividing procyclic promastigotes in the blood-fed midgut, with major changes in the abundance of mRNAs for surface proteins and metabolism. The post-blood meal-adapted nectomonad stage was characterized by the downregulation of cell cycle-related genes and the upregulation of stress- and starvation-related genes. Finally, the transcriptome of metacyclic promastigotes shifted to a more amastigote-like profile, suggesting their preadaptation to the intracellular host environment.
format	article
author	Ehud Inbar V. Keith Hughitt Laura A. L. Dillon Kashinath Ghosh Najib M. El-Sayed David L. Sacks
author_facet	Ehud Inbar V. Keith Hughitt Laura A. L. Dillon Kashinath Ghosh Najib M. El-Sayed David L. Sacks
author_sort	Ehud Inbar
title	The Transcriptome of <italic toggle="yes">Leishmania major</italic> Developmental Stages in Their Natural Sand Fly Vector
title_short	The Transcriptome of <italic toggle="yes">Leishmania major</italic> Developmental Stages in Their Natural Sand Fly Vector
title_full	The Transcriptome of <italic toggle="yes">Leishmania major</italic> Developmental Stages in Their Natural Sand Fly Vector
title_fullStr	The Transcriptome of <italic toggle="yes">Leishmania major</italic> Developmental Stages in Their Natural Sand Fly Vector
title_full_unstemmed	The Transcriptome of <italic toggle="yes">Leishmania major</italic> Developmental Stages in Their Natural Sand Fly Vector
title_sort	transcriptome of <italic toggle="yes">leishmania major</italic> developmental stages in their natural sand fly vector
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/0237bcd8c10b4444ae0c597be089eebf
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The Transcriptome of <italic toggle="yes">Leishmania major</italic> Developmental Stages in Their Natural Sand Fly Vector

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