Paratransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly's midgut environment.

Tsetse flies are vectors of parasitic African trypanosomes, the etiological agents of human and animal African trypanosomoses. Current disease control methods include fly-repelling pesticides, fly trapping, and chemotherapeutic treatment of infected people and animals. Inhibiting tsetse's abili...

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Autores principales:	Liu Yang, Brian L Weiss, Adeline E Williams, Emre Aksoy, Alessandra de Silva Orfano, Jae Hak Son, Yineng Wu, Aurelien Vigneron, Mehmet Karakus, Serap Aksoy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a67012c9d31b4f8583b37a982ea24325
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spelling	oai:doaj.org-article:a67012c9d31b4f8583b37a982ea243252021-12-02T19:59:37ZParatransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly's midgut environment.1553-73661553-737410.1371/journal.ppat.1009475https://doaj.org/article/a67012c9d31b4f8583b37a982ea243252021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009475https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Tsetse flies are vectors of parasitic African trypanosomes, the etiological agents of human and animal African trypanosomoses. Current disease control methods include fly-repelling pesticides, fly trapping, and chemotherapeutic treatment of infected people and animals. Inhibiting tsetse's ability to transmit trypanosomes by strengthening the fly's natural barriers can serve as an alternative approach to reduce disease. The peritrophic matrix (PM) is a chitinous and proteinaceous barrier that lines the insect midgut and serves as a protective barrier that inhibits infection with pathogens. African trypanosomes must cross tsetse's PM in order to establish an infection in the fly, and PM structural integrity negatively correlates with trypanosome infection outcomes. Bloodstream form trypanosomes shed variant surface glycoproteins (VSG) into tsetse's gut lumen early during the infection establishment, and free VSG molecules are internalized by the fly's PM-producing cardia. This process results in a reduction in the expression of a tsetse microRNA (miR275) and a sequential molecular cascade that compromises PM integrity. miRNAs are small non-coding RNAs that are critical in regulating many physiological processes. In the present study, we investigated the role(s) of tsetse miR275 by developing a paratransgenic expression system that employs tsetse's facultative bacterial endosymbiont, Sodalis glossinidius, to express tandem antagomir-275 repeats (or miR275 sponges). This system induces a constitutive, 40% reduction in miR275 transcript abundance in the fly's midgut and results in obstructed blood digestion (gut weights increased by 52%), a significant increase (p-value < 0.0001) in fly survival following infection with an entomopathogenic bacteria, and a 78% increase in trypanosome infection prevalence. RNA sequencing of cardia and midgut tissues from paratransgenic tsetse confirmed that miR275 regulates processes related to the expression of PM-associated proteins and digestive enzymes as well as genes that encode abundant secretory proteins. Our study demonstrates that paratransgenesis can be employed to study microRNA regulated pathways in arthropods that house symbiotic bacteria.Liu YangBrian L WeissAdeline E WilliamsEmre AksoyAlessandra de Silva OrfanoJae Hak SonYineng WuAurelien VigneronMehmet KarakusSerap AksoyPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 6, p e1009475 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Liu Yang Brian L Weiss Adeline E Williams Emre Aksoy Alessandra de Silva Orfano Jae Hak Son Yineng Wu Aurelien Vigneron Mehmet Karakus Serap Aksoy Paratransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly's midgut environment.
description	Tsetse flies are vectors of parasitic African trypanosomes, the etiological agents of human and animal African trypanosomoses. Current disease control methods include fly-repelling pesticides, fly trapping, and chemotherapeutic treatment of infected people and animals. Inhibiting tsetse's ability to transmit trypanosomes by strengthening the fly's natural barriers can serve as an alternative approach to reduce disease. The peritrophic matrix (PM) is a chitinous and proteinaceous barrier that lines the insect midgut and serves as a protective barrier that inhibits infection with pathogens. African trypanosomes must cross tsetse's PM in order to establish an infection in the fly, and PM structural integrity negatively correlates with trypanosome infection outcomes. Bloodstream form trypanosomes shed variant surface glycoproteins (VSG) into tsetse's gut lumen early during the infection establishment, and free VSG molecules are internalized by the fly's PM-producing cardia. This process results in a reduction in the expression of a tsetse microRNA (miR275) and a sequential molecular cascade that compromises PM integrity. miRNAs are small non-coding RNAs that are critical in regulating many physiological processes. In the present study, we investigated the role(s) of tsetse miR275 by developing a paratransgenic expression system that employs tsetse's facultative bacterial endosymbiont, Sodalis glossinidius, to express tandem antagomir-275 repeats (or miR275 sponges). This system induces a constitutive, 40% reduction in miR275 transcript abundance in the fly's midgut and results in obstructed blood digestion (gut weights increased by 52%), a significant increase (p-value < 0.0001) in fly survival following infection with an entomopathogenic bacteria, and a 78% increase in trypanosome infection prevalence. RNA sequencing of cardia and midgut tissues from paratransgenic tsetse confirmed that miR275 regulates processes related to the expression of PM-associated proteins and digestive enzymes as well as genes that encode abundant secretory proteins. Our study demonstrates that paratransgenesis can be employed to study microRNA regulated pathways in arthropods that house symbiotic bacteria.
format	article
author	Liu Yang Brian L Weiss Adeline E Williams Emre Aksoy Alessandra de Silva Orfano Jae Hak Son Yineng Wu Aurelien Vigneron Mehmet Karakus Serap Aksoy
author_facet	Liu Yang Brian L Weiss Adeline E Williams Emre Aksoy Alessandra de Silva Orfano Jae Hak Son Yineng Wu Aurelien Vigneron Mehmet Karakus Serap Aksoy
author_sort	Liu Yang
title	Paratransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly's midgut environment.
title_short	Paratransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly's midgut environment.
title_full	Paratransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly's midgut environment.
title_fullStr	Paratransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly's midgut environment.
title_full_unstemmed	Paratransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly's midgut environment.
title_sort	paratransgenic manipulation of a tsetse microrna alters the physiological homeostasis of the fly's midgut environment.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/a67012c9d31b4f8583b37a982ea24325
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Paratransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly's midgut environment.

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