{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:18:55Z","timestamp":1792624735950,"version":"4.5.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,6,19]]},"abstract":"<jats:p>\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    are widespread and abundant intracellular symbionts of arthropods and filarial nematodes. Their symbiotic relationships encompass obligate mutualism, commensalism, parasitism, and pathogenicity. A consequence of these diverse associations is that\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    encounter a wide range of host cells and intracellular immune defense mechanisms of invertebrates, which they must evade to maintain their populations and spread to new hosts. Here we show that autophagy, a conserved intracellular defense mechanism and regulator of cell homeostasis, is a major immune recognition and regulatory process that determines the size of\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    populations. The regulation of\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    populations by autophagy occurs across all distinct symbiotic relationships and can be manipulated either chemically or genetically to modulate the\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    population load. The recognition and activation of host autophagy is particularly apparent in rapidly replicating strains of\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    found in somatic tissues of\n                    <jats:italic>Drosophila<\/jats:italic>\n                    and filarial nematodes. In filarial nematodes, which host a mutualistic association with\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    , the use of antibiotics such as doxycycline to eliminate\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    has emerged as a promising approach to their treatment and control. Here we show that the activation of host nematode autophagy reduces bacterial loads to the same magnitude as antibiotic therapy; thus we identify a bactericidal mode of action targeting\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    that can be exploited for the development of chemotherapeutic agents against onchocerciasis, lymphatic filariasis, and heartworm.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1203519109","type":"journal-article","created":{"date-parts":[[2012,5,30]],"date-time":"2012-05-30T00:35:30Z","timestamp":1338338130000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":135,"title":["Autophagy regulates\n                    <i>Wolbachia<\/i>\n                    populations across diverse symbiotic associations"],"prefix":"10.1073","volume":"109","author":[{"given":"Denis","family":"Voronin","sequence":"first","affiliation":[{"name":"Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren A. N.","family":"Cook","sequence":"additional","affiliation":[{"name":"Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Steven","sequence":"additional","affiliation":[{"name":"Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,5,29]]},"reference":[{"key":"e_1_1_2_18_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-308X(05)60004-8"},{"key":"e_1_1_2_18_10_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1969"},{"key":"e_1_1_2_18_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60586-7"},{"key":"e_1_1_2_18_10_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2011.84"},{"key":"e_1_1_2_18_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2004.01.006"},{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-308X(05)60004-8"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.hdy.6800739"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1969"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.07.093"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1165326"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030121"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000475"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13199-010-0067-1"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2004.01.006"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002351"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5338"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.05.016"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500712200"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.01.016"},{"key":"e_1_3_3_15_2","unstructured":"A Mel\u00e9ndez B Levine Autophagy in C . elegans . 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