{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:49:25Z","timestamp":1792212565833,"version":"4.4.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T00:00:00Z","timestamp":1497312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T00:00:00Z","timestamp":1497312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The continued success of malaria control efforts requires the development, study and implementation of new technologies that circumvent insecticide resistance. We previously demonstrated that fungal pathogens can provide an effective delivery system for mosquitocidal or malariacidal biomolecules. Here we compared genes from arthropod predators encoding insect specific sodium, potassium and calcium channel blockers for their ability to improve the efficacy of\n                    <jats:italic>Metarhizium<\/jats:italic>\n                    against wild-caught, insecticide-resistant anophelines. Toxins expressed under control of a hemolymph-specific promoter increased fungal lethality to mosquitoes at spore dosages as low as one conidium per mosquito. One of the most potent, the EPA approved Hybrid (Ca\n                    <jats:sup>++<\/jats:sup>\n                    \/K\n                    <jats:sup>+<\/jats:sup>\n                    channel blocker), was studied for pre-lethal effects. These included reduced blood feeding behavior, with almost 100% of insects infected with ~6 spores unable to transmit malaria within 5 days post-infection, surpassing the World Health Organization threshold for successful vector control agents. Furthermore, recombinant strains co-expressing Hybrid toxin and AaIT (Na\n                    <jats:sup>+<\/jats:sup>\n                    channel blocker) produced synergistic effects, requiring 45% fewer spores to kill half of the mosquitoes in 5 days as single toxin strains. Our results identify a repertoire of toxins with different modes of action that improve the utility of entomopathogens as a technology that is compatible with existing insecticide-based control methods.\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-03399-0","type":"journal-article","created":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T10:35:58Z","timestamp":1496831758000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Improved efficacy of an arthropod toxin expressing fungus against insecticide-resistant malaria-vector mosquitoes"],"prefix":"10.1038","volume":"7","author":[{"given":"Etienne","family":"Bilgo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5721-7695","authenticated-orcid":false,"given":"Brian","family":"Lovett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niraj","family":"Bende","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn F.","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdoulaye","family":"Diabate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond J.","family":"St. Leger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,13]]},"reference":[{"key":"3399_CR1","unstructured":"Organization, W. H. & others. World Malaria Report 2015. WHO, Geneva (2015)."},{"key":"3399_CR2","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1016\/j.trstmh.2009.01.008","volume":"103","author":"KR Dabir\u00e9","year":"2009","unstructured":"Dabir\u00e9, K. R. et al. Distribution of pyrethroid and DDT resistance and the L1014F kdr mutation in Anopheles gambiae s.l. from Burkina Faso (West Africa). Trans. R. Soc. Trop. Med. Hyg. \n                           103, 1113\u20131120, doi:10.1016\/j.trstmh.2009.01.008 (2009).","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"3399_CR3","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1186\/1475-2875-8-299","volume":"8","author":"H Ranson","year":"2009","unstructured":"Ranson, H. et al. Insecticide resistance in Anopheles gambiae: data from the first year of a multi-country study highlight the extent of the problem. Malar. J. \n                           8, 299, doi:10.1186\/1475-2875-8-299 (2009).","journal-title":"Malar. J."},{"key":"3399_CR4","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s12936-015-1075-7","volume":"15","author":"HC Slater","year":"2016","unstructured":"Slater, H. C. et al. Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa. Malar. J. \n                           15, 10, doi:10.1186\/s12936-015-1075-7 (2016).","journal-title":"Malar. J."},{"key":"3399_CR5","doi-asserted-by":"crossref","unstructured":"Bhatt, S. et al. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature \n                           526, 207\u2013211 (2015).","DOI":"10.1038\/nature15535"},{"key":"3399_CR6","doi-asserted-by":"publisher","first-page":"e48412","DOI":"10.1371\/journal.pone.0048412","volume":"7","author":"M Namountougou","year":"2012","unstructured":"Namountougou, M. et al. Multiple Insecticide Resistance in Anopheles gambiae s.l. Populations from Burkina Faso, West Africa. PLoS One \n                           7, e48412, doi:10.1371\/journal.pone.0048412 (2012).","journal-title":"PLoS One"},{"key":"3399_CR7","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/S0300-9084(00)01177-9","volume":"82","author":"E Zlotkin","year":"2000","unstructured":"Zlotkin, E., Fishman, Y. & Elazar, M. AaIT: From neurotoxin to insecticide. Biochimie \n                           82, 869\u2013881, doi:10.1016\/S0300-9084(00)01177-9 (2000).","journal-title":"Biochimie"},{"key":"3399_CR8","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1038\/nbt1357","volume":"25","author":"C Wang","year":"2007","unstructured":"Wang, C. & St. Leger, R. J. A scorpion neurotoxin increases the potency of a fungal insecticide. Nat. Biotechnol. \n                           25, 1455\u20136, doi:10.1038\/nbt1357 (2007).","journal-title":"Nat. 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Pathol. \n                           91, 43\u201349, doi:10.1016\/j.jip.2005.10.006 (2006).","journal-title":"J. Invertebr. Pathol."},{"key":"3399_CR17","doi-asserted-by":"publisher","first-page":"e773","DOI":"10.1371\/journal.pntd.0000773","volume":"4","author":"SB Ogoma","year":"2010","unstructured":"Ogoma, S. B. et al. Screening Mosquito House Entry Points as a Potential Method for Integrated Control of Endophagic Filariasis, Arbovirus and Malaria Vectors. PLoS Negl. Trop. Dis. \n                           4, e773, doi:10.1371\/journal.pntd.0000773 (2010).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"3399_CR18","unstructured":"WHO [World Health Organization]. Guidelines for efficacy testing of spatial repellents. WHO\/HTM\/NTD\/WHOPES\/2013 (2013)."},{"key":"3399_CR19","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1128\/aem.58.10.3343-3346.1992","volume":"58","author":"BE Tabashnik","year":"1992","unstructured":"Tabashnik, B. E. 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