THE ROLE OF ANTIMICROBIAL PEPTIDE HBβ-C IN ICHTHYOPHTHIRIUS MULTIFILIIS RESISTANCE IN ALL-MALE AND HYBRID YELLOW CATFISH
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摘要: 为研究全雄黄颡鱼(Pelteobagrus fulvidraco)、瓦式黄颡鱼(Pelteobagrus vachelli)和杂交黄颡鱼(黄颡鱼P. fulvidraco♀×瓦氏黄颡鱼P. vachelli♂)对多子小瓜虫(Ichthyophthirius multifiliis)的抗性差异, 通过生物信息学分析黄颡鱼皮肤黏液蛋白质组, 发现其血红蛋白源抗菌肽(HBβ-C)位于血红蛋白β链HBβ的碳端, 共33个氨基酸。利用化学合成的不同浓度的HBβ-C肽段进行体外抗虫实验, 研究发现其能有效杀死滋养体、包囊体和掠食体阶段的多子小瓜虫, 其中15 µg/mL的HBβ-C能在3min内杀死所有滋养体。基因表达量分析显示, 在杂交黄颡鱼的鳃和皮肤组织中, HBβ的mRNA表达量高于全雄黄颡鱼; 但在应对小瓜虫感染的过程中, 全雄黄颡鱼的HBβ mRNA转录水平快速提升, 其表达水平和上升倍率显著高于杂交黄颡鱼。蛋白表达量分析显示, HBβ在全雄黄颡鱼鳃组织中的蛋白表达量明显高于杂交黄颡鱼。免疫荧光定位结果显示, 抗菌肽HBβ-C特异地在红细胞中表达, 可以分泌并附着在滋养体上。综上所述, 相对于杂交黄颡鱼, 全雄黄颡鱼中HBβ具有更高的翻译效率, 可以更高效地应对多子小瓜虫的感染。Abstract: All-male yellow catfish (Pelteobagrus fulvidraco) and hybrid yellow catfish (P. fulvidraco♀×P. vachelli♂) are the main breeding varieties of yellow catfish. The “white spot disease” caused by Ichthyophthirius multifiliis (Ich) is one of the main diseases of yellow catfish in China. Ich resistance assay was performed on all-male and hybrid yellow catfish, as well as the darkarbel catfish (P. vachelli). By bioinformatics analysis, we identified an antimicrobial peptide HBβ-C from the skin mucus proteome of yellow catfish, a 33 amino acid peptide derived from the C terminal of hemoglobin β chain (HBβ). The anti-parasitic test indicated that HBβ-C effectively killed the trophont, tomont and theront, especially in trophont stage, and 15 µg/mL HBβ-C killed all trophont within 3min. Gene expression analysis showed that the expression of HBβ mRNA in gill and skin of hybrid yellow catfish was higher than that of all-male yellow catfish. Ich challenge significantly increased HBβ mRNA level in all-male yellow catfish, which was higher than that of hybrid yellow catfish. Interestingly, the HBβ protein level in gill of all-male yellow catfish was higher than that in hybrid yellow catfish. Immunofluorescence results showed that the antimicrobial peptide HBβ-C was specifically expressed in red blood cells. After Ich infection, HBβ-C was secreted and attached to the trophont in skin and gill. Thus, our results revealed that all-male yellow catfish was much more resistant to Ich than hybrid yellow catfish. The high HBβ protein in all-male yellow catfish and its ability to kill all stages of Ich might be closely associated with the resistance of all-male yellow catfish to Ich.
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图 1 全雄黄颡鱼、杂交黄颡鱼和瓦式黄颡鱼感染多子小瓜虫的存活曲线图
Figure 1. The survival curves of all-male yellow catfish, hybrid yellow catfish and darkbarbel catfish after infected with Ichthyophthirius multifiliis
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图 2 全雄黄颡鱼和杂交黄颡鱼混合感染多子小瓜虫的存活曲线图
Figure 2. The survival curves of all-male yellow catfish and hybrid yellow catfish after infected with Ichthyophthirius multifiliis. All-male yellow catfish and hybrid yellow catfish were mixed together
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图 3 黄颡鱼HBβ基因cDNA全长及其预测的氨基酸序列
抗菌肽序列由下划线标出, 虚线框显示的序列是用来制备抗体的肽段
Figure 3. The cDNA sequence and deduced amino acid sequences of HBβ in yellow catfish
The antimicrobial peptide sequence is underlined, and the dashed box shows the peptide used to prepare antibody
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图 4 抗菌肽HBβ-C的螺旋轮分布和结构模型图
A. 蓝色圆代表带正电荷氨基酸, 红色圆代表带负电荷氨基酸, 黄色圆代表非极性氨基酸, 灰色圆代表极性氨基酸; B. 红色代表疏水性氨基酸, 蓝色代表亲水性氨基酸
Figure 4. The helical wheel distribution and structure model of the antimicrobial peptide HBβ-C
A. Blue circles represent positively charged amino acids, red circles represent negatively charged amino acids, yellow circles represent nonpolar amino acids, and grey circles represent polar amino acids; B. Red color represents hydrophobic amino acids and blue color represents hydrophilic amino acids
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图 5 HBβ在鳃和皮肤组织中的表达分析
A、B. HBβ在杂交黄颡鱼和全雄黄颡鱼的鳃(A)和皮肤(B)组织中的mRNA表达分析; C. HBβ在杂交黄颡鱼和全雄黄颡鱼的鳃组织中的蛋白表达分析; D. 使用Image J软件分析C图中HBβ/β-actin的相对比值
Figure 5. The relative expression of HBβ in gill and skin
A, B. The mRNA expression of HBβ in gill (A) and skin (B) of hybrid yellow catfish and all-male yellow catfish; C. The protein expression of HBβ in gill of hybrid yellow catfish and all-male yellow catfish. D. The relative ratio HBβ/β-actin was determined by band intensities that were analyzed by Image J software
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图 6 抗菌肽HBβ-C对不同生活史的多子小瓜虫的影响
A. 滋养体处理前; B. 50 µg/mL的HBβ-C处理后的滋养体; C. 包囊体处理前; D—F. 500 µg/mL的HBβ-C处理后的包囊体; G. 掠食体处理前; H. 125 µg/mL的HBβ-C处理后的掠食体
Figure 6. The effect of antimicrobial peptide HBβ-C on Ichthyophthirius multifiliis different life cycles
A. Untreated trophont; B. Trophont treated with 50 µg/mL HBβ-C; C. Untreated tomont; D—F. Tomont treated with 500 µg/mL HBβ-C; G. Untreated theront; H. Theront treated with 125 µg/mL HBβ-C
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图 7 HBβ免疫荧光定位及组织切片分析
A、C. 鳃组织的HBβ免疫组化分析; B、D. 鳃组织的HE染色分析; E. 皮肤的HBβ免疫组化分析; F. 皮肤的HE染色分析; 白色箭头所指为HBβ的阳性信号(红色荧光); DAPI 标记细胞核(蓝色荧光); RBC. 红细胞, BM. 基底膜
Figure 7. Detection of HBβ localization by immunohistochemistry and analysis of histological section
A, C. Immunohistochemistry analysis of HBβ in gill; B, D. HE staining analysis of gill; E. Immunohistochemistry analysis of HBβ in skin; F. HE staining analysis of skin; White arrowheads indicate the positive signal of HBβ (red fluorescence); Nucleus were stained with DAPI (blue fluorescence). RBC. red blood cell, BM. basement membrane
表 1 黄颡鱼感染多子小瓜虫每日死亡状况(尾)
Table 1 The daily dead status of yellow catfish after infected with Ichthyophthirius multifiliis
组别Group 使用鱼数量Number 每日死亡数Number of dead fish 死亡总数Total dead fish 2 3 4 5 6 7 8 9 10 11 12 13 14 全雄黄颡鱼a 60 0 0 0 0 0 1 0 0 0 0 0 0 0 1 全雄黄颡鱼b 60 0 0 0 0 0 2 0 0 0 0 0 0 0 2 全雄黄颡鱼c 60 0 0 0 0 0 0 0 0 0 0 0 0 0 0 杂交黄颡鱼a 60 0 1 1 4 12 13 5 11 5 2 3 0 3 60 杂交黄颡鱼b 60 0 0 4 8 16 10 11 4 0 4 0 3 0 60 杂交黄颡鱼c 60 0 2 1 3 11 19 8 9 1 3 0 3 0 60 瓦式黄颡鱼a 60 0 5 6 16 24 7 0 2 0 0 0 0 0 60 瓦式黄颡鱼b 60 3 4 2 13 11 20 6 1 0 0 0 0 0 60 瓦式黄颡鱼c 60 0 3 4 19 17 15 2 0 0 0 0 0 0 60 
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表 2 抗菌肽HBβ-C对不同生活史的多子小瓜虫体外影响
Table 2 The effect of antimicrobial peptide HBβ-C on the different life cycles of Ichthyophthirius multifiliis in vitro
多子小瓜虫生活史
Life cycle of ich最低杀虫浓度
PC100 (μg/mL)滋养体Trophont 15 包囊体Tomont >500 掠食体Theront 125 注: PC100为杀死所有寄生虫的最低浓度Note: PC100 was the lowest concentration that all parasites died
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