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Mass administration of drugs targeting the microfilarial stage has reduced transmission and eliminated these diseases in several countries but a macrofilaricidal drug that kills or sterilizes the adult worms is critically needed to eradicate the diseases. The causative agents of onchocerciasis and lymphatic filariasis are filarial worms that harbor the endosymbiotic bacterium\n                      <jats:italic>Wolbachia.<\/jats:italic>\n                      Because filarial worms depend on\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      for reproduction and survival, drugs targeting\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      hold great promise as a means to eliminate these diseases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To better understand the relationship between\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      and its worm host, adult\u00a0\n                      <jats:italic>Brugia pahangi<\/jats:italic>\n                      \u00a0were exposed to varying concentrations of doxycycline, minocycline, tetracycline and rifampicin\u00a0\n                      <jats:italic>in vitro<\/jats:italic>\n                      \u00a0and assessed for\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      numbers and worm motility. Worm motility was monitored using the Worminator system, and\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      titers were assessed by qPCR of the single copy gene\n                      <jats:italic>wsp<\/jats:italic>\n                      from\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      and\n                      <jats:italic>gst<\/jats:italic>\n                      from\n                      <jats:italic>Brugia<\/jats:italic>\n                      to calculate IC\n                      <jats:sub>50<\/jats:sub>\n                      s and in time course experiments\n                      <jats:italic>.<\/jats:italic>\n                      Confocal microscopy was also used to quantify\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      located at the distal tip region of worm ovaries to assess the effects of antibiotic treatment in this region of the worm where\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      are transmitted vertically to the microfilarial stage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Worms treated with higher concentrations of antibiotics had higher\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      titers, i.e. as antibiotic concentrations increased there was a corresponding increase in\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      titers. As the concentration of antibiotic increased, worms stopped moving and never recovered despite maintaining\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      titers comparable to controls. Thus, worms were rendered moribund by the higher concentrations of antibiotics but\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      persisted suggesting that these antibiotics may act directly on the worms at high concentration. Surprisingly, in contrast to these results, antibiotics given at low concentrations reduced\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      titers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      in\n                      <jats:italic>B. pahangi<\/jats:italic>\n                      display a counterintuitive dose response known as the \u201cEagle effect.\u201d This effect in\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      suggests a common underlying mechanism that allows diverse bacterial and fungal species to persist despite exposure to high concentrations of antimicrobial compounds. To our knowledge this is the first report of this phenomenon occurring in an intracellular endosymbiont,\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      , in its filarial host.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13071-020-04545-w","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T08:03:59Z","timestamp":1614153839000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Eagle effect in the Wolbachia-worm symbiosis"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2359-8354","authenticated-orcid":false,"given":"Christina A.","family":"Bulman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Chappell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Gunderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Beerntsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barton E.","family":"Slatko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy A.","family":"Sakanari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"4545_CR1","doi-asserted-by":"publisher","first-page":"e758","DOI":"10.1371\/journal.pntd.0000758","volume":"4","author":"F Landmann","year":"2010","unstructured":"Landmann F, Foster JM, Slatko B, Sullivan W. 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