{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T19:50:46Z","timestamp":1778961046975,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012611","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000}}],"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007487","name":"BASF Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007487","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH NIAID","award":["R01 AI056189"],"award-info":[{"award-number":["R01 AI056189"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Bacillus thuringiensis<\/jats:italic> (Bt) has been successfully used commercially for more than 60 years for biocontrol of insect pests. Since 1996, transgenic plants expressing Bt crystal (Cry) proteins have been used commercially to provide protection against insects that predate on corn and cotton. More recently, Bt Cry proteins that target nematodes have been discovered. One of these, Cry14Ab, has been expressed in transgenic soybean plants and found to provide significant protection against the soybean cyst nematode, <jats:italic>Heterodera glycines<\/jats:italic>. However, to date there has been no description of high-level resistance to any Cry14A family protein in nematodes. Here, we describe forward genetic screens to identify such mutants using the nematode <jats:italic>Caenorhabditis elegans<\/jats:italic>. Although non-conditional screens failed to identify highly resistant <jats:italic>C<\/jats:italic>. <jats:italic>elegans<\/jats:italic>, a conditional (temperature-sensitive) genetic screen identified one mutant, <jats:italic>bre-6(ye123)<\/jats:italic> (for <jats:bold><jats:italic>B<\/jats:italic><\/jats:bold>t protein <jats:bold><jats:italic>re<\/jats:italic><\/jats:bold>sistant), highly resistant to both Cry14Aa and Cry14Ab. The mutant comes at a high fitness cost, showing significant delays in growth and development and reduced fecundity. <jats:italic>bre-6(ye123)<\/jats:italic> hermaphrodites are only weakly resistant to copper intoxication, indicating that the mutant is not highly resistant to all insults. Backcrossing\u2014whole genome sequencing was used to identify the gene mutated in <jats:italic>ye123<\/jats:italic> as the nuclear hormone receptor <jats:italic>nhr-31<\/jats:italic>. RNAi, DNA rescue, and CRISPR analyses confirm that resistance to Cry14Aa intoxication in <jats:italic>bre-6(ye123)<\/jats:italic> is due to mutation of <jats:italic>nhr-31<\/jats:italic> and was renamed <jats:italic>nhr-31(ye123)<\/jats:italic>. As predicted for a mutation in this gene, <jats:italic>nhr-31(ye123)<\/jats:italic> animals showed significantly reduced expression of most of the subunits of the <jats:italic>C<\/jats:italic>. <jats:italic>elegans<\/jats:italic> vacuolar ATPase (vATPase). Mutants in the vATPase subunits <jats:italic>unc-32<\/jats:italic> and <jats:italic>vha-7<\/jats:italic> also show resistance to Cry14Aa and\/or Cry14Ab. These data demonstrate that <jats:italic>nhr-31<\/jats:italic> and the vATPase play a significant role in the intoxication of <jats:italic>C<\/jats:italic>. <jats:italic>elegans<\/jats:italic> by Cry14A family proteins, that reduction in vATPase levels result in high resistance to Cry14A family proteins, and that such resistance comes at a high fitness cost. Based on the relative difficulty of finding resistant mutants and the fitness cost associated with the vATPase pathway, our data suggest that transgenic Cry14Ab plants may hold up well to resistance by nematode parasites.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012611","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T17:35:58Z","timestamp":1729272958000},"page":"e1012611","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Resistance to Cry14A family Bacillus thuringiensis crystal proteins in Caenornabditis elegans operates via the nhr-31 transcription factor and vacuolar-type ATPase pathway"],"prefix":"10.1371","volume":"20","author":[{"given":"Youmie","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thanh-Thanh","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Durning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takao","family":"Ishidate","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozkan","family":"Aydemir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig C.","family":"Mello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore W.","family":"Kahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9741-3834","authenticated-orcid":true,"given":"Raffi V.","family":"Aroian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"ppat.1012611.ref001","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/j.1467-7652.2011.00595.x","article-title":"Bacillus thuringiensis: a century of research, development and commercial applications","volume":"9","author":"G Sanahuja","year":"2011","journal-title":"Plant Biotechnol J"},{"key":"ppat.1012611.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jip.2009.02.009","article-title":"Insecticidal activity of Bacillus thuringiensis crystal proteins","volume":"101","author":"K. van Frankenhuyzen","year":"2009","journal-title":"J Invertebr 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