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Galactosamine reduces sandfly gut protease activity through TOR downregulation and increases Lutzomyia susceptibility to Leishmania.
Insect Biochemistry and Molecular Biology ( IF 3.8 ) Pub Date : 2020-04-29 , DOI: 10.1016/j.ibmb.2020.103393
Tatiana Lima Silva Fernandes 1 , Adalberto Alves Pereira-Filho 1 , Denise Barguil Nepomuneno 1 , Tarcísio de Freitas Milagres 1 , Luccas Gabriel Ferreira Malta 1 , Grasielle Caldas D'Ávila Pessoa 1 , Leonardo Barbosa Koerich 1 , Marcos Horácio Pereira 1 , Ricardo Nascimento Araujo 1 , Nelder de Figueiredo Gontijo 1 , Mauricio Roberto Viana Sant'Anna 1
Affiliation  

In sandflies, males and females feed on carbohydrates but females must get a blood meal for egg maturation. Using artificial blood meals, this study aimed to understand how galactosamine interferes with sandfly digestive physiology. We also used galactosamine to manipulate the digestive physiology of Lutzomyia longipalpis to investigate its influence on sandfly digestion and Leishmania development within their insect vectors. Galactosamine was capable to reduce Lu. longipalpis trypsinolytic activity in a dose-dependent manner. This effect was specific to galactosamine as other similar sugars were not able to affect sandfly trypsin production. An excess of amino acids supplemented with the blood meal and 15 mM galactosamine was able to abrogate the reduction of the trypsinolytic activity caused by galactosamine, suggesting this phenomenon may be related to an impairment of amino acid detection by sandfly enterocytes. The TOR inhibitor rapamycin reduces trypsin activity in the L. longipalpis midgut. Galactosamine reduces the phosphorylation of the TOR pathway repressor 4EBP, downregulating TOR activity in the gut of L. longipalpis. Galactosamine reduces sandfly oviposition, causes an impact on sandfly longevity and specifically reduces sandfly gut proteases whereas increasing α-glycosidase activity. The administration of 15 and 30 mM galactosamine increased the number of promastigote forms of Le. mexicana and Le. infantum in galactosamine-treated L. longipalpis. Our results showed that galactosamine influences amino acid sensing, reduces sandfly gut protease activity through TOR downregulation, and benefits Leishmania growth within the Lu. longipalpis gut.

中文翻译:

半乳糖胺可通过TOR下调降低沙蝇肠蛋白酶的活性,并增加Lutzomyia对利什曼原虫的易感性。

在沙f中,雄性和雌性以碳水化合物为食,但雌性必须获得血粉以使卵成熟。本研究使用人造血粉了解半乳糖胺如何干扰沙sand的消化生理。我们还使用半乳糖胺操纵长形夜蛾的消化生理,以研究其对昆虫载体中沙fly消化和利什曼原虫发育的影响。半乳糖胺能够还原Lu。longipalpis的胰蛋白酶溶解活性呈剂量依赖性。这种作用是对半乳糖胺特有的,因为其他类似的糖不能影响sand蝇胰蛋白酶的产生。补充了血粉和15 mM半乳糖胺的过量氨基酸能够消除由半乳糖胺引起的胰蛋白酶溶解活性的降低,提示这种现象可能与沙fly肠细胞的氨基酸检测受损有关。TOR抑制剂雷帕霉素可降低长双乳猪中肠的胰蛋白酶活性。半乳糖胺可降低TOR通路阻遏物4EBP的磷酸化,从而下调长形乳杆菌肠道中的TOR活性。半乳糖胺减少了沙蝇的产卵,对沙蝇的寿命产生了影响,并特别降低了沙蝇肠中的蛋白酶,同时增加了α-糖苷酶的活性。施用15和30 mM的半乳糖胺可增加Le的前鞭毛体形式的数量。墨西哥和勒。半乳糖胺处理的L. longipalpis中的婴儿。我们的结果表明,半乳糖胺可影响氨基酸的感应,通过TOR的下调降低沙棘肠蛋白酶的活性,并有利于Lu中利什曼原虫的生长。longipalpis肠。
更新日期:2020-04-29
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