{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:08:58Z","timestamp":1791468538358,"version":"4.3.4"},"reference-count":110,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100007904","name":"Texas A and M University","doi-asserted-by":"publisher","award":["505320-90360"],"award-info":[{"award-number":["505320-90360"]}],"id":[{"id":"10.13039\/100007904","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007904","name":"Texas A and M University","doi-asserted-by":"publisher","award":["505320-90360"],"award-info":[{"award-number":["505320-90360"]}],"id":[{"id":"10.13039\/100007904","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Mycolactone is a cytotoxic lipid metabolite produced by <jats:italic>Mycobacterium ulcerans<\/jats:italic>, the environmental pathogen responsible for Buruli ulcer, a neglected tropical disease. <jats:italic>Mycobacterium ulcerans<\/jats:italic> is prevalent in West Africa, particularly found in lentic environments, where mosquitoes also occur. Researchers hypothesize mosquitoes could serve as a transmission mechanism resulting in infection by <jats:italic>M<\/jats:italic>. <jats:italic>ulcerans<\/jats:italic> when mosquitoes pierce skin contaminated with <jats:italic>M<\/jats:italic>. <jats:italic>ulcerans<\/jats:italic>. The interplay between the pathogen, mycolactone, and mosquito is only just beginning to be explored. A triple-choice assay was conducted to determine the host-seeking preference of <jats:italic>Aedes aegypti<\/jats:italic> between <jats:italic>M<\/jats:italic>. <jats:italic>ulcerans<\/jats:italic> wildtype (MU, mycolactone active) and mutant (MU<jats:sup>lac-<\/jats:sup>, mycolactone inactive). Both qualitative and quantitative differences in volatile organic compounds\u2019 (VOCs) profiles of MU and MU<jats:sup>lac-<\/jats:sup> were determined by GC-MS. Additionally, we evaluated the interplay between <jats:italic>Ae<\/jats:italic>. <jats:italic>aegypti<\/jats:italic> proximity and <jats:italic>M<\/jats:italic>. <jats:italic>ulcerans<\/jats:italic> mRNA expression. The results showed that mosquito attraction was significantly greater (126.0%) to an artificial host treated with MU than MU<jats:sup>lac-<\/jats:sup>. We found that MU and MU<jats:sup>lac<\/jats:sup> produced differential profiles of VOCs associated with a wide range of biological importance from quorum sensing (QS) to human odor components. RT-qPCR assays showed that mycolactone upregulation was 24-fold greater for MU exposed to <jats:italic>Ae<\/jats:italic>. <jats:italic>aegypti<\/jats:italic> in direct proximity. Transcriptome data indicated significant induction of ten chromosomal genes of MU involved in stress responses and membrane protein, compared to MU<jats:sup>lac-<\/jats:sup> when directly having access to or in near mosquito proximity. Our study provides evidence of possible interkingdom interactions between unicellular and multicellular species that MU present on human skin is capable of interreacting with unrelated species (i.e., mosquitoes), altering its gene expression when mosquitoes are in direct contact or proximity, potentially impacting the production of its VOCs, and consequently leading to the stronger attraction of mosquitoes toward human hosts. This study elucidates interkingdom interactions between viable <jats:italic>M<\/jats:italic>. <jats:italic>ulcerans<\/jats:italic> bacteria and <jats:italic>Ae<\/jats:italic>. <jats:italic>aegypti<\/jats:italic> mosquitoes, which rarely have been explored in the past. Our finding opens new doors for future research in terms of disease ecology, prevalence, and pathogen dispersal outside of the <jats:italic>M<\/jats:italic>. <jats:italic>ulcerans<\/jats:italic> system.<\/jats:p>","DOI":"10.1371\/journal.pone.0289768","type":"journal-article","created":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T17:38:34Z","timestamp":1691084314000},"page":"e0289768","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Behavioral interplay between mosquito and mycolactone produced by Mycobacterium ulcerans and bacterial gene expression induced by mosquito proximity"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6931-7653","authenticated-orcid":true,"given":"Dongmin","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawni L.","family":"Crippen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laxmi","family":"Dhungel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6186-2208","authenticated-orcid":true,"given":"Pablo J.","family":"Delclos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery K.","family":"Tomberlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather R.","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,8,3]]},"reference":[{"key":"pone.0289768.ref001","volume-title":"Medical and veterinary entomology","author":"DS Kettle","year":"1984"},{"key":"pone.0289768.ref002","doi-asserted-by":"crossref","first-page":"4623","DOI":"10.1128\/AEM.68.9.4623-4628.2002","article-title":"Aquatic insects as a vector for Mycobacterium ulcerans","volume":"68","author":"L Marsollier","year":"2002","journal-title":"Appl Environ Microbiol"},{"key":"pone.0289768.ref003","volume-title":"Investing to overcome the global impact of neglected tropical diseases: third WHO report on neglected tropical diseases 2015","author":"World Health Organization","year":"2015"},{"key":"pone.0289768.ref004","first-page":"785","article-title":"Mycobacterium ulcerans disease","volume":"83","author":"TS Van der Werf","year":"2005","journal-title":"Bull World Health Organ"},{"key":"pone.0289768.ref005","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.3201\/eid2512.190427","article-title":"Global epidemiology of buruli ulcer, 2010\u20132017, and analysis of 2014 WHO programmatic targets","volume":"25","author":"TF Omansen","year":"2019","journal-title":"Emerg Infect Dis"},{"key":"pone.0289768.ref006","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/02763869.2019.1693231","article-title":"The Global Health Observatory data repository","volume":"39","author":"E. 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