Department of Entomology, Texas A&M University, College Station, Texas, United States of America.
Southern Plains Agricultural Research Center, Agricultural Research Service, USDA, College Station, Texas, United States of America.
PLoS One. 2023 Aug 3;18(8):e0289768. doi: 10.1371/journal.pone.0289768. eCollection 2023.
Mycolactone is a cytotoxic lipid metabolite produced by Mycobacterium ulcerans, the environmental pathogen responsible for Buruli ulcer, a neglected tropical disease. Mycobacterium ulcerans 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 M. ulcerans when mosquitoes pierce skin contaminated with M. 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 of Aedes aegypti between M. ulcerans wildtype (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 between Ae. aegypti proximity and M. ulcerans mRNA 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 MUlac 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 Ae. aegypti in 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 viable M. ulcerans bacteria and Ae. aegypti 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 M. ulcerans system.
Mycolactone 是一种细胞毒性脂质代谢物，由 Mycobacterium ulcerans 产生，Mycobacterium ulcerans 是导致伯利兹溃疡的环境病原体，伯利兹溃疡是一种被忽视的热带病。Mycobacterium ulcerans 在西非很普遍，特别是在池塘等蚊子也存在的静止环境中。研究人员假设，当蚊子叮咬沾有 Mycobacterium ulcerans 的皮肤时，蚊子可能成为一种传播机制，导致感染 Mycobacterium ulcerans。病原体、mycolactone 和蚊子之间的相互作用才刚刚开始被探索。进行了三重选择测定，以确定埃及伊蚊对 Mycobacterium ulcerans 野生型（MU，mycolactone 活跃）和突变型（MUlac-，mycolactone 不活跃）的宿主选择偏好。通过 GC-MS 确定了 MU 和 MUlac-挥发性有机化合物（VOCs）谱的定性和定量差异。此外，我们还评估了埃及伊蚊接近度与 Mycobacterium ulcerans mRNA 表达之间的相互作用。结果表明，与用 MUlac-处理的人工宿主相比，蚊子对 MU 的吸引力明显更大（126.0%）。我们发现，MU 和 MUlac 产生了与从群体感应（QS）到人类气味成分等广泛生物学重要性相关的不同 VOCs 图谱。RT-qPCR 测定表明，当 MU 直接暴露于埃及伊蚊时，mycolactone 的上调幅度增加了 24 倍。与 MUlac-相比，当 MU 直接接触或接近蚊子时，其染色体上涉及应激反应和膜蛋白的 10 个基因的转录本显著诱导。我们的研究提供了证据，证明在单细胞和多细胞物种之间可能存在跨领域相互作用，即在人体皮肤上存在的 MU 能够与无关物种（即蚊子）相互作用，当蚊子直接接触或接近时，改变其基因表达，可能会影响其 VOC 的产生，从而导致蚊子对人类宿主的更强吸引力。本研究阐明了有活力的 Mycobacterium ulcerans 细菌与埃及伊蚊之间的跨领域相互作用，过去很少对此进行探索。我们的发现为疾病生态学、流行范围以及病原体在 Mycobacterium ulcerans 系统之外的传播等方面的未来研究开辟了新的途径。
