The gut microbiota of insects has been shown to regulate host detoxification enzymes. However, the potential regulatory mechanisms involved remain unknown. Here, we report that gut bacteria increase insecticide resistance by activating the cap “n” collar isoform-C (CncC) pathway through enzymatically generated reactive oxygen species (ROS) in Bactrocera dorsalis. We demonstrated that Enterococcus casseliflavus and Lactococcus lactis, two lactic acid (LA)-producing bacteria, increase the resistance of B. dorsalis to β-cypermethrin by regulating cytochrome P450 (P450) enzymes and α-glutathione S-transferase (GST) activities. These gut symbionts also induced the expression of CncC and muscle aponeurosis fibromatosis (Maf). BdCncC knockdown led to a decrease in resistance caused by gut bacteria. Ingestion of the ROS scavenger vitamin C (VC) in resistant strain (RS) affected the expression of BdCncC/BdKeap1/BdMafK, resulting in reduced P450 and GST activity. Furthermore, feeding with E. casseliflavus or L. lactis showed that BdNOX5 increased ROS production, and BdNOX5 knockdown affected the expression of the BdCncC/BdMafK pathway and detoxification genes. Moreover, LA feeding activated the ROS-associated regulation of P450 and GST activity. Collectively, our findings indicate that symbiotic gut bacteria modulate intestinal detoxification pathways by affecting physiological biochemistry, thus providing new insights into the involvement of insect gut microbes in the development of insecticide resistance.

中文翻译：

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乳酸菌调节 CncC 途径增强东方果蝇对高效氯氰菊酯的抗性

昆虫的肠道微生物群已被证明可以调节宿主的解毒酶。然而，所涉及的潜在监管机制仍然未知。在这里，我们报告肠道细菌通过在橘小实蝇中酶促产生的活性氧（ROS）激活帽“n”领亚型-C（CncC）途径来增强杀虫剂抗药性。我们证明卡塞尔黄肠球菌和乳酸乳球菌这两种产乳酸（LA）的细菌通过调节细胞色素 P450（P450）酶和 α-谷胱甘肽 S-转移酶（GST）活性来增加桔小实蝇对 β-氯氰菊酯的耐药性。这些肠道共生体还诱导 CncC 和肌肉腱膜纤维瘤病 (Maf) 的表达。 BdCncC 敲除导致肠道细菌抵抗力下降。抗性菌株 (RS) 摄入 ROS 清除剂维生素 C (VC) 会影响 BdCncC/BdKeap1/BdMafK 的表达，导致 P450 和 GST 活性降低。此外，饲喂 E. cassseliflavus 或 L.lactis 表明，BdNOX5 增加了 ROS 的产生，并且 BdNOX5 敲低影响了 BdCncC/BdMafK 途径和解毒基因的表达。此外，LA 喂养激活了 P450 和 GST 活性的 ROS 相关调节。总的来说，我们的研究结果表明，共生肠道细菌通过影响生理生化来调节肠道解毒途径，从而为昆虫肠道微生物参与杀虫剂抗性的发展提供了新的见解。