{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T06:46:43Z","timestamp":1775890003912,"version":"3.50.1"},"posted":{"date-parts":[[2025,1,26]]},"group-title":"Pathology","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T00:00:00Z","timestamp":1737849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,26]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  The discovery of the endosymbiotic bacteria\n                  <jats:italic>Wolbachia<\/jats:italic>\n                  as an obligate symbiont of filarial nematodes has led to antibiotic-based treatments for filarial diseases. While lab and clinical studies have yielded promising results, recent animal studies reveal that\n                  <jats:italic>Wolbachia<\/jats:italic>\n                  levels may rebound following treatment with suboptimal doses of the antibiotic rifampicin. Previous work showed that a likely source of the bacterial rebound in females were dense clusters of\n                  <jats:italic>Wolbachia<\/jats:italic>\n                  in ovarian tissue. The number, size, and density of these\n                  <jats:italic>Wolbachia<\/jats:italic>\n                  clusters were not diminished despite antibiotic treatment. Here we define the cellular characteristics of the\n                  <jats:italic>Wolbachia<\/jats:italic>\n                  clusters in\n                  <jats:italic>Brugia pahangi<\/jats:italic>\n                  (wBp) and identify drugs that also target them. We have evidence that the\n                  <jats:italic>Wolbachia<\/jats:italic>\n                  clusters originate from newly formed sheath cells adjacent to the ovarian Distal Tip Cells. The dramatically enlarged volume of an infected sheath cell is strikingly similar to endosymbiont-induced bacteriocytes found in many insect species. Ultrastructural analysis reveals that the clustered\n                  <jats:italic>Wolbachia<\/jats:italic>\n                  present within the sheath cells exhibit a distinct morphology and form direct connections with the oocyte membrane and possibly the cytoplasm. This includes membrane-based channels providing a connection between\n                  <jats:italic>Wolbachia<\/jats:italic>\n                  -infected sheath cells and oocytes. We also determined that the\n                  <jats:italic>Wolbachia<\/jats:italic>\n                  within the sheath cells are either quiescent or replicating at a very low rate. Screens of known antibiotics and other drugs revealed that two drugs, Fexinidazole and Corallopyronin A, significantly reduced the number of clustered\n                  <jats:italic>Wolbachia<\/jats:italic>\n                  located within the sheath cells.\n                <\/jats:p>","DOI":"10.1101\/2025.01.23.634442","type":"posted-content","created":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T14:55:12Z","timestamp":1737903312000},"source":"Crossref","is-referenced-by-count":0,"title":["Fexinidazole and Corallopyronin A target\n                  <i>Wolbachia<\/i>\n                  -infected sheath cells present in filarial nematodes"],"prefix":"10.64898","author":[{"given":"Laura","family":"Chappell","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology University of California, Santa Cruz, CA 95064, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Peguero","sequence":"additional","affiliation":[{"name":"Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R","family":"Conner","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sommer","family":"Fowler","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology University of California, Santa Cruz, CA 95064, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon","family":"Cooper","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Pfarr","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achim","family":"Hoerauf","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Lustigman","sequence":"additional","affiliation":[{"name":"Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy","family":"Sakanari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1756-4174","authenticated-orcid":false,"given":"William","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology University of California, Santa Cruz, CA 95064, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041022513978000_2025.01.23.634442v1.1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.1034066"},{"key":"2026041022513978000_2025.01.23.634442v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/s12154-008-0003-5"},{"key":"2026041022513978000_2025.01.23.634442v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/s0020-7519(98)00200-8"},{"key":"2026041022513978000_2025.01.23.634442v1.4","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.2460\/ajvr.1975.36.08.1153","article-title":"Influence of the anthelmintic mebendazole on microtubules and intracellular organelle movement in nematode intestinal cells","volume":"36","year":"1975","journal-title":"Am. 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