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While lab. and clinical studies have yielded promising results, recent animal studies revealed that\n                    <jats:italic>\n                      <jats:italic>Wolbachia<\/jats:italic>\n                    <\/jats:italic>\n                    levels rebound following treatment with the antibiotic rifampicin. Previous work revealed that a potential source of the bacterial rebound in female worms were dense clusters of\n                    <jats:italic>\n                      <jats:italic>Wolbachia<\/jats:italic>\n                    <\/jats:italic>\n                    in ovarian tissue. The number, size, and density of these\n                    <jats:italic>\n                      <jats:italic>Wolbachia<\/jats:italic>\n                    <\/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 target them. We show that the\n                    <jats:italic>\n                      <jats:italic>Wolbachia<\/jats:italic>\n                    <\/jats:italic>\n                    clusters originate from newly formed sheath cells adjacent to the distal tip cell. The dramatically enlarged volume of a\n                    <jats:italic>\n                      <jats:italic>Wolbachia<\/jats:italic>\n                    <\/jats:italic>\n                    -infected sheath cell is strikingly similar to endosymbiont-induced bacteriocytes found in many insect species. Ultrastructural analysis reveals that the clustered\n                    <jats:italic>\n                      <jats:italic>Wolbachia<\/jats:italic>\n                    <\/jats:italic>\n                    present within the sheath cells have a distinct morphology from those present within the oocytes, and that the sheath cell membrane appears to have interdigitations with the adjacent oocyte membrane. This includes membrane-based channels that provide a connection between\n                    <jats:italic>\n                      <jats:italic>Wolbachia<\/jats:italic>\n                    <\/jats:italic>\n                    -infected sheath cells and oocytes. We determined that the\n                    <jats:italic>\n                      <jats:italic>Wolbachia<\/jats:italic>\n                    <\/jats:italic>\n                    within the sheath cells are either quiescent or replicating at a very low rate. Screens of 11 known antibiotics and other drugs revealed that Fexinidazole, Corallopyronin A and Rapamycin reduced the number of\n                    <jats:italic>\n                      <jats:italic>Wolbachia<\/jats:italic>\n                    <\/jats:italic>\n                    clusters infecting sheath cells but only Fexinidazole and Corallopyronin A showed a highly significant difference (p\u2009&lt;\u20090.0001) compared to the control group.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012929","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T18:05:33Z","timestamp":1757354733000},"page":"e1012929","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Fexinidazole and Corallopyronin A target Wolbachia-infected sheath cells present in filarial nematodes"],"prefix":"10.1371","volume":"21","author":[{"given":"Laura","family":"Chappell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Peguero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Conner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sommer","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon S.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Pfarr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Hoerauf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lustigman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Sakanari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1756-4174","authenticated-orcid":true,"given":"William","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"issue":"9","key":"ppat.1012929.ref001","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.pt.2024.07.005","article-title":"The 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