Pietri Jose E, Potts Rashaun
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
Insects. 2021 Mar 30;12(4):303. doi: 10.3390/insects12040303.
Bed bugs are globally important pests and there is an ongoing need for the development and improvement of bed bug control tools. Though promising against other insect pests, the exploration of biological methods for bed bug control is limited. Previously, we identified several species of bacteria that have entomopathogenic effects against bed bugs when ingested. We also described the conservation of several antibacterial responses in bed bugs, including the expression of immune effector genes regulated by NF-kB transcription factors through the Toll and immune deficiency (IMD) signaling pathways. Accordingly, we predicted that chemical inhibition of NF-kB signaling could reduce bed bug resistance to orally provisioned entomopathogenic bacteria, potentially improving their effectiveness as biological control agents. In the present study, we administered four small molecule inhibitors of NF-kB signaling (BMS345541, IKK16, IMD0354, Takinib) to bed bugs by feeding them in a blood meal. We then quantified basal mortality and mortality in response to oral infection with two different entomopathogenic bacteria ( and ). None of the NF-kB signaling inhibitors tested increased mortality above control levels when administered alone, suggesting a lack of direct toxicity. However, one inhibitor (IKK16) significantly enhanced the rate of mortality from oral infection with . Enhanced mortality was independent of direct effects of IKK16 on growth in vitro but was associated with higher bacterial loads in vivo (i.e., reduced resistance). Together, these results provide new insight into the regulation of the bed bug immune system and suggest that administration of entomopathogens in combination with inhibition of immune signaling pathways to reduce infection resistance may be effective for biological control of bed bugs.
臭虫是全球重要的害虫，持续需要开发和改进臭虫控制工具。尽管对其他害虫有前景，但用于臭虫控制的生物方法的探索有限。此前，我们鉴定了几种细菌物种，当被臭虫摄入时对其具有昆虫病原性作用。我们还描述了臭虫中几种抗菌反应的保守性，包括通过Toll和免疫缺陷（IMD）信号通路由NF-κB转录因子调节的免疫效应基因的表达。因此，我们预测对NF-κB信号的化学抑制可以降低臭虫对口服给予的昆虫病原细菌的抗性，潜在地提高它们作为生物控制剂的有效性。在本研究中，我们通过在血餐中喂食的方式给臭虫施用了四种NF-κB信号的小分子抑制剂（BMS345541、IKK16、IMD0354、Takinib）。然后我们量化了基础死亡率以及对两种不同昆虫病原细菌口服感染的死亡率。单独施用时，所测试的NF-κB信号抑制剂均未使死亡率高于对照水平，表明缺乏直接毒性。然而，一种抑制剂（IKK16）显著提高了口服感染[细菌名称缺失]后的死亡率。死亡率的提高与IKK16对[细菌名称缺失]体外生长的直接影响无关，但与体内更高的细菌载量相关（即抗性降低）。总之，这些结果为臭虫免疫系统的调节提供了新的见解，并表明将昆虫病原体与免疫信号通路抑制联合施用以降低感染抗性可能对臭虫的生物控制有效。
