{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:37:25Z","timestamp":1784954245977,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009770","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000}}],"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["5R44AI131806-03"],"award-info":[{"award-number":["5R44AI131806-03"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    PfSPZ Vaccine against malaria is composed of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    (Pf) sporozoites (SPZ) manufactured using aseptically reared\n                    <jats:italic>Anopheles stephensi<\/jats:italic>\n                    mosquitoes. Immune response genes of\n                    <jats:italic>Anopheles<\/jats:italic>\n                    mosquitoes such as Leucin-Rich protein (LRIM1), inhibit\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    SPZ development (sporogony) in mosquitoes by supporting melanization and phagocytosis of ookinetes. With the aim of increasing PfSPZ infection intensities, we generated an\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>stephensi LRIM1<\/jats:italic>\n                    knockout line,\n                    <jats:italic>\u0394aslrim1<\/jats:italic>\n                    , by embryonic genome editing using CRISPR-Cas9.\n                    <jats:italic>\u0394aslrim1<\/jats:italic>\n                    mosquitoes had a significantly increased midgut bacterial load and an altered microbiome composition, including elimination of commensal acetic acid bacteria. The alterations in the microbiome caused increased mosquito mortality and unexpectedly, significantly reduced sporogony. The survival rate of\n                    <jats:italic>\u0394aslrim1<\/jats:italic>\n                    mosquitoes and their ability to support PfSPZ development, were partially restored by antibiotic treatment of the mosquitoes, and fully restored to baseline when\n                    <jats:italic>\u0394aslrim1<\/jats:italic>\n                    mosquitoes were produced aseptically. Deletion of\n                    <jats:italic>LRIM1<\/jats:italic>\n                    also affected reproductive capacity: oviposition, fecundity and male fertility were significantly compromised. Attenuation in fecundity was not associated with the altered microbiome. This work demonstrates that LRIM1\u2019s regulation of the microbiome has a major impact on vector competence and longevity of\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>stephensi<\/jats:italic>\n                    . Additionally,\n                    <jats:italic>LRIM1<\/jats:italic>\n                    deletion identified an unexpected role for this gene in fecundity and reduction of sperm transfer by males.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009770","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T13:34:30Z","timestamp":1637069670000},"page":"e1009770","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Knockout of Anopheles stephensi immune gene LRIM1 by CRISPR-Cas9 reveals its unexpected role in reproduction and vector competence"],"prefix":"10.1371","volume":"17","author":[{"given":"Ehud","family":"Inbar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham G.","family":"Eappen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Alford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8130-6516","authenticated-orcid":true,"given":"William","family":"Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6970-1396","authenticated-orcid":true,"given":"Robert A.","family":"Harrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Hosseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumana","family":"Chakravarty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Kim Lee","family":"Sim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F.","family":"Billingsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0700-9505","authenticated-orcid":true,"given":"Stephen L.","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"issue":"1","key":"ppat.1009770.ref001","doi-asserted-by":"crossref","first-page":"97","DOI":"10.4161\/hv.6.1.10396","article-title":"Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria.","volume":"6","author":"SL Hoffman","year":"2010","journal-title":"Hum Vaccin"},{"issue":"Pt 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