de_Oliveira, Mozaniel Santana
(Ed.)
Mycolactone is a cytotoxic lipid metabolite produced byMycobacterium ulcerans, the environmental pathogen responsible for Buruli ulcer, a neglected tropical disease.Mycobacterium ulceransis 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 byM.ulceranswhen mosquitoes pierce skin contaminated withM.ulcerans. 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 ofAedes aegyptibetweenM.ulceranswildtype (MU, mycolactone active) and mutant (MUlac-, mycolactone inactive). Both qualitative and quantitative differences in volatile organic compounds’ (VOCs) profiles of MU and MUlac-were determined by GC-MS. Additionally, we evaluated the interplay betweenAe.aegyptiproximity andM.ulceransmRNA expression. The results showed that mosquito attraction was significantly greater (126.0%) to an artificial host treated with MU than MUlac-. We found that MU and MUlacproduced 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 toAe.aegyptiin direct proximity. Transcriptome data indicated significant induction of ten chromosomal genes of MU involved in stress responses and membrane protein, compared to MUlac-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 viableM.ulceransbacteria andAe.aegyptimosquitoes, 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 theM.ulceranssystem.
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