Disruption of blood meal-responsive serpins prevents Ixodes scapularis from feeding to repletion.
Disruption of blood meal-responsive serpins prevents Ixodes scapularis from feeding to repletion.
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DOI：
10.1016/j.ttbdis.2018.01.001
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发表时间：
2018-03
影响因子：
3.2
通讯作者：
Mulenga A
中科院分区：
文献类型：
--
作者：
Bakshi M;Kim TK;Mulenga A
丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂）被认为介导蜱逃避宿主丝氨酸蛋白酶介导的防御途径，如炎症和血液凝固。本研究通过定量(q)RT-PCR和RNAi沉默分析，描述了11种与若虫和成虫蜱食有关的血食反应蛇形蛋白的特征和靶标验证。考虑到大量的靶标，我们使用组合（co） RNAi沉默来破坏两组(G)中的候选蛇形蛋白：基于氨基酸身份的7个高度相同和4个不相同的蛇形蛋白，在这里分别称为GI和GII。我们发现，将GI和GII的co-dsRNA注射到未喂养的肩胛骨蜱若虫和成虫体内，可以抑制同源丝氨酸丝氨酸mRNA的表达。我们发现，破坏GII，而不是破坏GI蛇蛋白，显著降低了若虫和成虫的取食效率。GII蛇形蛋白转录本的敲低导致在24-48小时内发生的稚蜱和成蜱的死亡率分别为≤40%和71%。这是很重要的，因为观察到的致死率在蜱虫喂养期之前，而蜱虫传播的病原体占主导地位。我们怀疑一些GII蛇形蛋白（S9, S17， S19和S32）在蜱虫脱离过程中发挥作用，因为在脱离过程中，注射的GII co-dsRNA的口器上覆盖着一层白色凝胶状组织，可能是蜱虫水泥锥。通常情况下，蜱在脱离后不会在其口器上保留组织。此外，GII蛇形蛋白的破坏减少了蜱虫血粉的大小和成年蜱虫将血粉转化为卵的能力。我们讨论了我们的数据与蜱进食生理学，并得出结论，一些GII蛇形蛋白是抗蜱疫苗开发的潜在目标。
Serine protease inhibitors (serpins) are thought to mediate the tick’s evasion of the host’s serine protease-mediated defense pathways such as inflammation and blood clotting. This study describes characterization and target validation of 11 blood meal-responsive serpins that are associated with nymph and adult Ixodes scapularis tick feeding as revealed by quantitative (q)RT-PCR and RNAi silencing analyses. Given the high number of targets, we used combinatorial (co) RNAi silencing to disrupt candidate serpins in two groups (G): seven highly identical and four non-identical serpins based on amino acid identities, here after called GI and GII respectively. We show that injection of both GI and GII co-dsRNA into unfed nymph and adult I. scapularis ticks triggered suppression of cognate serpin mRNA. We show that disruption of GII, but not GI serpins significantly reduced feeding efficiency of both nymph and adult I. scapularis ticks. Knockdown of GII serpin transcripts caused significant respective mortalities of ≤ 40 and 71% of nymphal and adult ticks that occurred within 24–48 h of attachment. This is significant, as the observed lethality preceded the tick feeding period when transmission of tick borne pathogens is predominant. We suspect that some of the GII serpins (S9, S17, S19 and S32) play roles in the tick detachment process in that upon detachment, mouthparts of GII co-dsRNA injected were covered with a whitish gel-like tissue that could be the tick cement cone. Normally, ticks do not retain tissue on their mouthparts upon detachment. Furthermore, disruption of GII serpins reduced tick blood meal sizes and the adult tick’s ability to convert the blood meal to eggs. We discuss our data with reference to tick feeding physiology and conclude that some of the GII serpins are potential targets for anti-tick vaccine development.
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DOI：
10.4269/ajtmh.2004.71.3.0700268
发表时间：
2004-09-01
影响因子：
3.3
作者：
Ebel, GD;Kramer, LD
通讯作者：
Kramer, LD
影响因子：
3.7
作者：
Adamson, Steven W.;Browning, Rebecca E.;Karim, Shahid
通讯作者：
Karim, Shahid
影响因子：
3.2
作者：
Ferrolho, Joana;Antunes, Sandra;Domingos, Ana
通讯作者：
Domingos, Ana
血蜱扇头蜱抗凝蛋白 Rhipilin-1 的表征。
影响因子：
2.2
作者：
Gao, Xiao;Shi, Lei;Zhou, Jinlin
通讯作者：
Zhou, Jinlin
影响因子：
56.9
作者：
BURGDORFER, W;BARBOUR, AG;DAVIS, JP
通讯作者：
DAVIS, JP