Traverso Lucila, Lavore Andrés, Sierra Ivana, Palacio Victorio, Martinez-Barnetche Jesús, Latorre-Estivalis José Manuel, Mougabure-Cueto Gaston, Francini Flavio, Lorenzo Marcelo G, Rodríguez Mario Henry, Ons Sheila, Rivera-Pomar Rolando V
Laboratorio de Neurobiología de Insectos, Centro Regional de Estudios Genómicos, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
Centro de Bioinvestigaciones (CeBio) and Centro de Investigación y Transferencia del Noroeste de Buenos Aires (CITNOBA-CONICET), Universidad Nacional del Noroeste de la Provincia de Buenos Aires, Pergamino, Argentina.
PLoS Negl Trop Dis. 2017 Feb 15;11(2):e0005313. doi: 10.1371/journal.pntd.0005313. eCollection 2017 Feb.
Triatomine insects are vectors of Trypanosoma cruzi, a protozoan parasite that is the causative agent of Chagas' disease. This is a neglected disease affecting approximately 8 million people in Latin America. The existence of diverse pyrethroid resistant populations of at least two species demonstrates the potential of triatomines to develop high levels of insecticide resistance. Therefore, the incorporation of strategies for resistance management is a main concern for vector control programs. Three enzymatic superfamilies are thought to mediate xenobiotic detoxification and resistance: Glutathione Transferases (GSTs), Cytochromes P450 (CYPs) and Carboxyl/Cholinesterases (CCEs). Improving our knowledge of key triatomine detoxification enzymes will strengthen our understanding of insecticide resistance processes in vectors of Chagas' disease.
The discovery and description of detoxification gene superfamilies in normalized transcriptomes of three triatomine species: Triatoma dimidiata, Triatoma infestans and Triatoma pallidipennis is presented. Furthermore, a comparative analysis of these superfamilies among the triatomine transcriptomes and the genome of Rhodnius prolixus, also a triatomine vector of Chagas' disease, and other well-studied insect genomes was performed. The expression pattern of detoxification genes in R. prolixus transcriptomes from key organs was analyzed. The comparisons reveal gene expansions in Sigma class GSTs, CYP3 in CYP superfamily and clade E in CCE superfamily. Moreover, several CYP families identified in these triatomines have not yet been described in other insects. Conversely, several groups of insecticide resistance related enzymes within each enzyme superfamily are reduced or lacking in triatomines. Furthermore, our qRT-PCR results showed an increase in the expression of a CYP4 gene in a T. infestans population resistant to pyrethroids. These results could point to an involvement of metabolic detoxification mechanisms on the high levels of pyrethroid resistance detected in triatomines from the Gran Chaco ecoregion.
Our results help to elucidate the potential insecticide resistance mechanisms in vectors of Chagas' disease and provide new relevant information for this field. This study shows that metabolic resistance might be a contributing cause of the high pyrethroid resistance observed in wild T. infestans populations from the Gran Chaco ecoregion, area in which although subjected to intense pyrethroid treatments, vector control has failed. This study opens new avenues for further functional studies on triatomine detoxification mechanisms.
锥蝽昆虫是克氏锥虫的传播媒介，克氏锥虫是一种原生动物寄生虫，是恰加斯病的病原体。这是一种被忽视的疾病，影响拉丁美洲约800万人。至少两种锥蝽存在多种对拟除虫菊酯耐药的种群，这表明锥蝽具有产生高水平杀虫剂抗性的潜力。因此，纳入抗性管理策略是病媒控制项目的主要关注点。三个酶超家族被认为介导异源生物解毒和抗性：谷胱甘肽S-转移酶（GSTs）、细胞色素P450（CYPs）和羧酸酯酶/胆碱酯酶（CCEs）。增进我们对锥蝽关键解毒酶的了解，将加强我们对恰加斯病传播媒介中杀虫剂抗性过程的理解。
本文介绍了在三种锥蝽物种（二色锥蝽、侵扰锥蝽和苍白锥蝽）的标准化转录组中解毒基因超家族的发现和描述。此外，还对这些超家族在锥蝽转录组、同样是恰加斯病传播媒介的南美锥蝽的基因组以及其他经过充分研究的昆虫基因组之间进行了比较分析。分析了南美锥蝽关键器官转录组中解毒基因的表达模式。比较结果显示，在西格玛类谷胱甘肽S-转移酶、细胞色素P450超家族中的CYP3以及羧酸酯酶/胆碱酯酶超家族的E进化枝中存在基因扩增。此外，在这些锥蝽中鉴定出的几个细胞色素P450家族在其他昆虫中尚未有描述。相反，每个酶超家族中与杀虫剂抗性相关的几组酶在锥蝽中减少或缺失。此外，我们的定量逆转录聚合酶链反应结果显示，在对拟除虫菊酯耐药的侵扰锥蝽种群中，一个细胞色素P450 4基因的表达增加。这些结果可能表明，代谢解毒机制参与了在大查科生态区的锥蝽中检测到的高水平拟除虫菊酯抗性。
我们的结果有助于阐明恰加斯病传播媒介中潜在的杀虫剂抗性机制，并为该领域提供新的相关信息。本研究表明，代谢抗性可能是在大查科生态区野生侵扰锥蝽种群中观察到的高水平拟除虫菊酯抗性产生原因之一，在该地区，尽管进行了大量拟除虫菊酯处理，但病媒控制仍告失败。本研究为锥蝽解毒机制的进一步功能研究开辟了新途径。
