Drosophila melanogaster transcriptional response to agrochemicals

While much attention has been devoted to understanding the transcriptional changes underlying resistance to insecticides, comparatively little is known about the transcriptional response of naive insects to agrochemicals. In this study, we analyze the transcriptomic response of Drosophila melanogaster to nine agrochemicals using a robust method that goes beyond classical replication standards. Our findings demonstrate that exposure to piperonyl butoxide (PBO), but not to eight other compounds, elicits a robust transcriptional response in a wild-type strain of Drosophila melanogaster. PBO exposure leads to the upregulation of a subset of Cyps, GSTs, UGTs and EcKls. This response is both time and dose-dependent, suggesting that the degree of inhibition of P450 activity correlates with the magnitude of the transcriptional response. Furthermore, the upregulation of these enzymes is excluded from reproductive organs. Additionally, different sets of genes are regulated in the digestive/secretory tract and the carcass. Our results suggest that P450s play a role in metabolizing yet unidentified endogenous compounds and are involved in an as-yet-unknown physiological regulatory feedback loop.

尽管学界已对杀虫剂抗性相关的转录调控变化开展了大量研究，但针对未暴露昆虫对农用化学品的转录应答的认知却相对匮乏。本研究采用超越经典重复实验标准的稳健分析方法，对黑腹果蝇（Drosophila melanogaster）接触9种农用化学品后的转录组应答进行了分析。研究结果表明，在黑腹果蝇野生型品系中，仅增效醚（piperonyl butoxide, PBO）暴露可引发强烈的转录应答，其余8种化合物均无此效应。增效醚暴露会诱导部分CYP家族基因（Cyps）、谷胱甘肽S-转移酶（GSTs）、尿苷二磷酸葡萄糖醛酸转移酶（UGTs）及EcKls的表达上调。该应答呈现时间与剂量依赖性，提示细胞色素P450（P450）的活性抑制程度与转录应答的强度呈正相关。此外，上述酶类的上调表达并未发生于生殖器官；且消化/分泌道与躯体的基因调控模式存在显著差异，二者所调控的基因集各不相同。本研究结果提示，细胞色素P450家族在代谢尚未鉴定的内源性化合物中发挥作用，并参与了一个尚未阐明的生理调控反馈环路。