{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T09:16:22Z","timestamp":1782638182821,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009475","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000}}],"reference-count":102,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T00:00:00Z","timestamp":1623196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AI139525"],"award-info":[{"award-number":["R01AI139525"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Li foundation"},{"DOI":"10.13039\/100001246","name":"Ambrose Monell Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    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\u2019s ability to transmit trypanosomes by strengthening the fly\u2019s 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\u2019s 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\u2019s gut lumen early during the infection establishment, and free VSG molecules are internalized by the fly\u2019s PM-producing cardia. This process results in a reduction in the expression of a tsetse microRNA (\n                    <jats:italic>miR275<\/jats:italic>\n                    ) 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\n                    <jats:italic>miR275<\/jats:italic>\n                    by developing a paratransgenic expression system that employs tsetse\u2019s facultative bacterial endosymbiont,\n                    <jats:italic>Sodalis glossinidius<\/jats:italic>\n                    , to express tandem antagomir\n                    <jats:italic>-275<\/jats:italic>\n                    repeats (or\n                    <jats:italic>miR275<\/jats:italic>\n                    sponges). This system induces a constitutive, 40% reduction in\n                    <jats:italic>miR275<\/jats:italic>\n                    transcript abundance in the fly\u2019s midgut and results in obstructed blood digestion (gut weights increased by 52%), a significant increase (p-value &lt; 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\n                    <jats:italic>miR275<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009475","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T14:22:38Z","timestamp":1623248558000},"page":"e1009475","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Paratransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly\u2019s midgut environment"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-5268","authenticated-orcid":true,"given":"Liu","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8433-0060","authenticated-orcid":true,"given":"Adeline E.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2797-0328","authenticated-orcid":true,"given":"Emre","family":"Aksoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"de Silva Orfano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hak","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yineng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4986-6465","authenticated-orcid":true,"given":"Aurelien","family":"Vigneron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9460-1215","authenticated-orcid":true,"given":"Mehmet","family":"Karakus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-143X","authenticated-orcid":true,"given":"Serap","family":"Aksoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"issue":"10","key":"ppat.1009475.ref001","doi-asserted-by":"crossref","first-page":"e1859","DOI":"10.1371\/journal.pntd.0001859","article-title":"Estimating 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