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研究生:顏秀如
研究生(外文):Yen, Hsiu-Ju
論文名稱:以斑馬魚側線毛細胞作為研究耳毒性物質之動物模式
論文名稱(外文):Using Lateral Line Hair Cell of Zebrafish as a Model Animal for Ototoxins
指導教授:林豊益洪君琳
指導教授(外文):Lin, Li-YihHorng, Jiun-Lin
學位類別:博士
校院名稱:國立臺灣師範大學
系所名稱:生命科學系
學門:生命科學學門
學類:生物學類
論文出版年:2021
畢業學年度:109
語文別:中文
論文頁數:67
中文關鍵詞:側線毛細胞環境汙染物抗生素奈米顆粒 掃描式離子選擇電極耳毒性
外文關鍵詞:lateral line hair cellenvironmental contaminantsantibioticsnanoparticlesscanning ion-selective electrode techniqueototoxicity
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隨科技進步,奈米物質使用日益增加,其中奈米銀和奈米銅是其中最被廣泛使用的奈米材料,多應用於治療劑、抗菌劑、化妝品或工業之用。而曾被限用於局部治療之高腎毒性抗生素colistin,隨著革蘭氏陰性細菌之抗藥性出現,以及後線有效抗生素之短缺,全球使用量亦隨之上升。近年來,許多研究開始發現各種藥品、抗生素和個人護理產品存在於各式水域系統,被公認為屬於新興的環境污染物。隨著奈米顆粒廣泛使用以及colistin後線抗生素全球用量的不斷攀升,並以各種方式進入環境及水域系統。此類新興環境汙染物暴露之可能性,及其對生物或環境的毒性影響也是我們亟需思考的問題。然而目前並無適當的毒理研究證實此類新興環境汙染物對水生動物的負面影響,特別是耳毒性方面之研究。
由於魚類側線系統位於皮膚,會直接暴露外來物質,且其側線毛細胞於表面易於觀察,加上側線神經丘中之毛細胞的結構及功能與人類內耳的機械感官性毛細胞極為相似,故其側線系統之毛細胞應可作為測試潛在有毒物質之耳毒性的合理模式。在本研究中,我們使用斑馬魚胚胎之側線毛細胞,以研究早期暴露此類新興環境汙染物對斑馬魚胚胎本身及其側線毛細胞之影響。我們將斑馬魚胚胎自受孕後連續暴露96小時於不同濃度之特定環境污染物(包括抗生素colistin、奈米銀、奈米銅),觀察其存活率、胚胎孵化率、外觀及側線毛細胞的數量及功能影響。
抗生素colistin之暴露明顯降低了胚胎存活率,此降低與其濃度具明顯相關性;暴露於抗生素colistin 96小時後50%致死之濃度(LC50)值為3.0 μM或3.5 mg/L,但並未改變其孵化率和體長。同時,經由觀測FM1-43標記之毛細胞數量下降,及使用掃描式離子選擇電極技術偵測側線毛細胞處之鈣離子流減少,證實抗生素colistin於濃度≥ 0.1 μM時,已影響其側線毛細胞之功能。以此斑馬魚胚胎側線毛細胞模式,亦發現常見的奈米銀、奈米銅造成斑馬魚胚胎之存活率下降,此降低亦與暴露濃度具明顯相關性;暴露於奈米銀、奈米銅96小時之LC50分別為6.1 ppm(56.5 μM)和2.61 ppm(41.1 μM)。當奈米銀濃度≥ 1 ppm(9.3 μM)或奈米銅濃度≥ 0.01 ppm(0.16 μM),FM1-43標記的毛細胞數量會開始減少,並出現微觀結構改變;當奈米銀濃度≥ 0.1 ppm(0.9 μM)或奈米銅濃度≥ 0.01 ppm(0.16 μM),雖毛細胞數量無顯著下降,但掃描式離子選擇電極技術測得之毛細胞鈣離子流已經開始明顯下降。
此研究證明,藉助以掃描式電子顯微鏡觀測FM1-43標記之斑馬魚側線毛細胞數量,合併掃描式離子選擇電極技術測量之毛細胞功能,來作為研究耳毒性物質之斑馬魚模型之可行性。
With nanotechnology advances, nanomaterials are widely applied in tissue engineering, imaging, surface texturing, and preservatives in cosmetics. Among all nanomaterials, the most common nanoparticles are silver (AgNPs) and copper nanoparticles (CuNPs). In addition, colistin, one of the few cationic antimicrobial peptides, was mostly used in local treatment due to its renal toxicity related to systemic use in the past few decades. Due to the emergence of multi-resistant gram-negative bacterial infections, and a shortage of new-generation antimicrobial agents, colistin gains attention as a last-line antibiotic. Its global consumption rate increases greatly in the last decade. With the presence antibiotics, chemotherapeutic agents, personal care products in the aquatic environment system, those agents were recognized as emerging environmental contaminants in recent years. But their toxicological effects on aquatic animals have not been properly investigated, especially the hair cell toxicity of lateral line, which involves a wide range of behaviors on aquatic animals. The impairment of lateral line may furtherly impact their survival.
Due to neuromasts of lateral line system in the fish being located in the skin and directly contacting environmental exposure, and the structure and functions of hair cells in lateral line neuromasts mimicking those of mechanosensory hair cells in the inner ear of humans, lateral line system in zebrafish is suitable for investigating potential hair cell damage of the emerging environmental contaminants. In this study, we examined the survival, hatching, morphological changes and hair cell toxicity of selected contaminants, including colistin, AgNPs or CuNPs, on zebrafish embryos, which were incubated in different concentrations of these selective agents during 0~96 hour post fertilization.
Colistin decreased the survival rate in a dose-dependent manner (LC50 was 3.0 μM or 3.5 mg/L), but it did not change the hatching rate, and body length of embryos. However, colistin impaired lateral-line hair cells in the skin of embryos. Colistin (at ≥ 0.1 μM) decreased the number of FM1-43-labeled hair cells. Ca2+ influxes at hair bundles of hair cells were measured with a scanning ion-selective microelectrode technique (SIET) to evaluate the function of hair cells. The reduced mechanotransduction-mediated Ca2+ influx at hair bundles suggests that sublethal concentrations of colistin can impair lateral line function. Both AgNPs and CuNPs were found to also cause toxic effects in zebrafish embryos in a dose-dependent manner. Values of the 96-h 50% lethal concentration (LC50) of AgNPs and CuNPs were 6.1 ppm (56.5 μM) and 2.61 ppm (41.1 μM), respectively. The number of FM1-43-labeled hair cells and the microstructure of hair bundles were significantly impaired by AgNPs [≥ 1 ppm (9.3 μM)] and CuNPs [≥ 0.01 ppm (0.16 μM)]. AgNPs [≥ 0.1 ppm (0.9 μM)] and CuNPs [≥ 0.01 ppm (0.16 μM)] were both found to significantly reduce Ca2+ influxes.
This study revealed that lateral-line hair cells of zebrafish are susceptible to colistin, AgNPs and CuNPs functionally and morphologically at different specific concentration. By combining SIET to detect Ca2+ influxes through mechanoelectrical transducer channel and FM1-43 staining with scanning electron microscopy, lateral line hair cells in zebrafish could be used as a model animal for investigating ototoxins.
第一章 引言 1
第一節、在毒理學研究中使用斑馬魚動物模式之優勢 1
第二節、使用側線毛細胞之優勢 1
第三節、魚類側線毛細胞受傷後之影響 2
第四節、使用掃描式離子選擇電極技術檢測毛細胞功能改變之優勢 3
第五節、Colistin的使用、相關毒性和抗藥性 4
第六節、日常生活中奈米顆粒之使用及其毒性 6
第七節、環境中存在藥物及奈米顆粒之證據 8
第八節、研究動機 9

第二章 研究目的 11
第一節、檢驗斑馬魚胚胎在0〜96 hpf暴露於三種新興環境汙染物(包括colistin、奈米銀和奈米銅)之存活率、孵化率和形態變化 11
第二節、檢驗在亞致死劑量下,此三種水中污染物(包括colistin、奈米銀和奈米銅)對斑馬魚胚胎皮膚之側線毛細胞的影響 11

第三章 研究材料與方法 13
第一節、斑馬魚 13
第二節、測試物質之製備和處理 14
第三節、存活率和孵化率之測量 15
第四節、斑馬魚外觀變化與體長測量 15
第五節、毛細胞數量之測量 16
第六節、以掃描電子顯微鏡(SEM)觀察毛細胞外觀 16
第七節、掃描式離子選擇電極技術(SIET) 17
第八節、L1神經丘上Ca2+離子流之測量 18
第九節、統計分析 19

第四章 研究結果 21
第一節、Colistin和奈米顆粒對斑馬魚胚胎存活率和孵化率之影響 21
第二節、Colistin和奈米顆粒對斑馬魚胚胎形態以及體長之影響 23
第三節、Colistin和奈米顆粒對斑馬魚胚胎側線毛細胞形態之影響 24
第四節、Colistin和奈米顆粒對斑馬魚胚胎側線毛細胞數量之影響 25
第五節、Colistin和奈米顆粒對斑馬魚胚胎側線毛細胞功能之影響 26

第五章 討論 28
第一節、Colistin暴露對斑馬魚胚胎及側線毛細胞之影響 28
第二節、奈米銀之暴露對斑馬魚胚胎存活率、孵化率及體長之影響 30
第三節、奈米銅之暴露對斑馬魚胚胎存活率、孵化率及體長之影響 32
第四節、奈米金屬與金屬離子毒性之差異與相關性 33
第五節、先前奈米金屬造成耳毒性之相關研究與比較 35
第六節、使用SIET研究側線毛細胞較其他檢測方式之優勢 36
第七節、耳毒性之傷害來自於吞食或皮膚之接觸 37
第八節、側線毛細胞作為耳毒性物質模式之可行性 38
第九節、此偵測到之耳毒性傷害與環境相關濃度比較 39
第十節、未來可以進行研究之方向 39

第六章 結論 42

第七章 參考文獻 43

第八章 圖1〜12 54
Asharani, P.V., Lian Wu, Y., Gong, Z., Valiyaveettil, S., 2008. Toxicity of silver nanoparticles in zebrafish models. Nanotechnology 19, 255102.

Asharani, P.V., Lianwu, Y., Gong, Z., Valiyaveettil, S., 2011. Comparison of the toxicity of silver, gold and platinum nanoparticles in developing zebrafish embryos. Nanotoxicology 5, 43-54.

Bai, W., Tian, W., Zhang, Z., He, X., Ma, Y., Liu, N., Chai, Z., 2010. Effects of copper nanoparticles on the development of zebrafish embryos. J Nanosci Nanotechnol 10, 8670-8676.

Bilberg, K., Hovgaard, M.B., Besenbacher, F., Baatrup, E., 2012. In Vivo Toxicity of Silver Nanoparticles and Silver Ions in Zebrafish (Danio rerio). J Toxicol 2012, 293784.

Cabello, F.C., Tomova, A., Ivanova, L., Godfrey, H.P., 2017. Aquaculture and mcr Colistin Resistance Determinants. mBio 8, e01229-17.

Caracciolo, A.B., Topp, E., Grenni, P., 2015. Pharmaceuticals in the environment: biodegradation and effects on natural microbial communities. A review. J Pharm Biomed Anal 106, 25-36.

Chakraborty, C., Sharma, A.R., Sharma, G., Lee, S.S., 2016. Zebrafish: A complete animal model to enumerate the nanoparticle toxicity. J Nanobiotechnology 14, 65.

Chio, C.P., Chen, W.Y., Chou, W.C., Hsieh, N.H., Ling, M.P., Liao, C.M., 2012. Assessing the potential risks to zebrafish posed by environmentally relevant copper and silver nanoparticles. Sci Total Environ 420, 111-118.

Coffin, A.B., Reinhart, K.E., Owens, K.N., Raible, D.W., Rubel, E.W., 2009. Extracellular divalent cations modulate aminoglycoside-induced hair cell death in the zebrafish lateral line. Hear Res 253, 42-51.

de Oliveira, R.C.S., Oliveira, R., Rodrigues, M.A.C., de Farias, N.O., Sousa-Moura, D., Nunes, N.A., Andrade, T.S., Grisolia, C.K., 2020. Lethal and Sub-lethal Effects of Nitrofurantoin on Zebrafish Early-Life Stages. Water, Air, & Soil Pollution 231, 54.

Falagas, M.E., Kasiakou, S.K., 2005. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis 40, 1333-1341.

Froehlicher, M., Liedtke, A., Groh, K.J., Neuhauss, S.C., Segner, H., Eggen, R.I., 2009. Zebrafish (Danio rerio) neuromast: promising biological endpoint linking developmental and toxicological studies. Aquat Toxicol 95, 307-319.

Gale, J.E., Marcotti, W., Kennedy, H.J., Kros, C.J., Richardson, G.P., 2001. FM1-43 dye behaves as a permeant blocker of the hair-cell mechanotransducer channel. J Neurosci 21, 7013-7025.

Garber, S.S., Messerli, M.A., Hubert, M., Lewis, R., Hammar, K., Indyk, E., Smith, P.J., 2005. Monitoring Cl- movement in single cells exposed to hypotonic solution. J Membr Biol 203, 101-110.

Gelband, H., Miller-Petrie, M., Pant, S., Gandra, S., Levinson, J., Barter, D., White, A., Laxminarayan, R., 2015. The state of the world's antibiotics 2015. Center for Disease Dynamics, Economics & Policy, 2015. CDDEP: Washington, D.C.

Ghysen, A., Dambly-Chaudiere, C., 2004. Development of the zebrafish lateral line. Curr Opin Neurobiol 14, 67-73.

Ghysen, A., Dambly-Chaudiere, C., 2007. The lateral line microcosmos. Genes Dev 21, 2118-2130.

Grenni, P., Ancona, V., Caracciolo, A.B., 2018. Ecological effects of antibiotics on natural ecosystems: A review. Microchemical Journal 136, 25-39.

Griffitt, R.J., Weil, R., Hyndman, K.A., Denslow, N.D., Powers, K., Taylor, D., Barber, D.S., 2007. Exposure to copper nanoparticles causes gill injury and acute lethality in zebrafish (Danio rerio). Environ Sci Technol 41, 8178-8186.

Griffitt, R.J., Luo, J., Gao, J., Bonzongo, J.C., Barber, D.S., 2008. Effects of particle composition and species on toxicity of metallic nanomaterials in aquatic organisms. Environ Toxicol Chem 27, 1972-1978.

Hagenmaier, H.E., 1974. The hatching process in fish embryos. IV. The enzymological properties of a highly purified enzyme (chorionase) from the hatching fluid of the rainbow trout, Salmo gairdneri Rich. Comp Biochem Physiol B 49, 313-324.

Horng, J.L., Chao, P.L., Chen, P.Y., Shih, T.H., Lin, L.Y., 2015. Aquaporin 1 Is Involved in Acid Secretion by Ionocytes of Zebrafish Embryos through Facilitating CO2 Transport. PLoS One 10, e0136440.

Hung, G.Y., Wu, C.L., Chou, Y.L., Chien, C.T., Horng, J.L., Lin, L.Y., 2019. Cisplatin exposure impairs ionocytes and hair cells in the skin of zebrafish embryos. Aquat Toxicol 209, 168-177.

Kazmierczak, P., Muller, U., 2012. Sensing sound: molecules that orchestrate mechanotransduction by hair cells. Trends Neurosci 35, 220-229.

Klein, E.Y., Van Boeckel, T.P., Martinez, E.M., Pant, S., Gandra, S., Levin, S.A., Goossens, H., Laxminarayan, R., 2018. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proc Natl Acad Sci U S A 115, E3463-E3470.

Kolpin, D.W., Furlong, E.T., Meyer, M.T., Thurman, E.M., Zaugg, S.D., Barber, L.B., Buxton, H.T., 2002. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999-2000: a national reconnaissance. Environ Sci Technol 36, 1202-1211.

Kulpa, M., Bak-Coleman, J., Coombs, S., 2015. The lateral line is necessary for blind cavefish rheotaxis in non-uniform flow. The Journal of Experimental Biology 218, 1603-1612.

Kummerer, K., 2009. Antibiotics in the aquatic environment--a review--part I. Chemosphere 75, 417-434.

Lacave, J.M., Retuerto, A., Vicario-Pares, U., Gilliland, D., Oron, M., Cajaraville, M.P., Orbea, A., 2016. Effects of metal-bearing nanoparticles (Ag, Au, CdS, ZnO, SiO2) on developing zebrafish embryos. Nanotechnology 27, 325102.

Lee, C.Y., Horng, J.L., Chen, P.Y., Lin, L.Y., 2019. Silver nanoparticle exposure impairs ion regulation in zebrafish embryos. Aquat Toxicol 214, 105263.

Li, L., Hu, L., Zhou, Q., Huang, C., Wang, Y., Sun, C., Jiang, G., 2015. Sulfidation as a natural antidote to metallic nanoparticles is overestimated: CuO sulfidation yields CuS nanoparticles with increased toxicity in medaka (Oryzias latipes) embryos. Environ Sci Technol 49, 2486-2495.

Lin, A.Y., Lin, C.F., Tsai, Y.T., Lin, H.H., Chen, J., Wang, X.H., Yu, T.H., 2010. Fate of selected pharmaceuticals and personal care products after secondary wastewater treatment processes in Taiwan. Water Sci Technol 62, 2450-2458.

Lin, A.Y., Tsai, Y.T., 2009. Occurrence of pharmaceuticals in Taiwan's surface waters: impact of waste streams from hospitals and pharmaceutical production facilities. Sci Total Environ 407, 3793-3802.

Lin, L.Y., Hung, G.Y., Yeh, Y.H., Chen, S.W., Horng, J.L., 2019. Acidified water impairs the lateral line system of zebrafish embryos. Aquat Toxicol 217, 105351.

Lin, L.Y., Pang, W., Chuang, W.M., Hung, G.Y., Lin, Y.H., Horng, J.L., 2013. Extracellular Ca2+ and Mg2+ modulate aminoglycoside blockade of mechanotransducer channel-mediated Ca2+ entry in zebrafish hair cells: an in vivo study with the SIET. Am J Physiol Cell Physiol 305, C1060-1068.

Lin, L.Y., Yeh, Y.H., Hung, G.Y., Lin, C.H., Hwang, P.P., Horng, J.L., 2018. Role of Calcium-Sensing Receptor in Mechanotransducer-Channel-Mediated Ca2+ Influx in Hair Cells of Zebrafish Larvae. Front Physiol 9, 649.

Lin, L.Y., Zheng, J.A., Huang, S.C., Hung, G.Y., Horng, J.L., 2020. Ammonia exposure impairs lateral-line hair cells and mechanotransduction in zebrafish embryos. Chemosphere 257, 127170.

Lin, Y.H., Hung, G.Y., Wu, L.C., Chen, S.W., Lin, L.Y., Horng, J.L., 2015. Anion exchanger 1b in stereocilia is required for the functioning of mechanotransducer channels in lateral-line hair cells of zebrafish. PLoS One 10, e0117041.

Liu, S.T., Tsung, L., Horng, J.L., Lin, L.Y., 2013. Proton-facilitated ammonia excretion by ionocytes of medaka (Oryzias latipes) acclimated to seawater. Am J Physiol Regul Integr Comp Physiol 305, R242-251.

Liu, Y.Y., Wang, Y., Walsh, T.R., Yi, L.X., Zhang, R., Spencer, J., Doi, Y., Tian, G., Dong, B., Huang, X., Yu, L.F., Gu, D., Ren, H., Chen, X., Lv, L., He, D., Zhou, H., Liang, Z., Liu, J.H., Shen, J., 2016. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 16, 161-168.

Putri, M.S.A., Lou, C.H., Syai’in, M., Ou, S.H., Wang, Y.C., 2018. Long-term river water quality trends and pollution source apportionment in Taiwan. Water 10, 1394.

Massarsky, A., Dupuis, L., Taylor, J., Eisa-Beygi, S., Strek, L., Trudeau, V.L., Moon, T.W., 2013. Assessment of nanosilver toxicity during zebrafish (Danio rerio) development. Chemosphere 92, 59-66.

McIntyre, R.A., 2012. Common nano-materials and their use in real world applications. Sci Prog 95, 1-22.

McNeil, P.L., Boyle, D., Henry, T.B., Handy, R.D., Sloman, K.A., 2014. Effects of metal nanoparticles on the lateral line system and behaviour in early life stages of zebrafish (Danio rerio). Aquat Toxicol 152, 318-323.

Mekdara, P.J., Schwalbe, M.A.B., Coughlin, L.L., Tytell, E.D., 2018. The effects of lateral line ablation and regeneration in schooling giant danios. The Journal of Experimental Biology 221, jeb175166.

Meyers, J.R., MacDonald, R.B., Duggan, A., Lenzi, D., Standaert, D.G., Corwin, J.T., Corey, D.P., 2003. Lighting up the senses: FM1-43 loading of sensory cells through nonselective ion channels. J Neurosci 23, 4054-4065.

Morizono, T., 1990. Toxicity of ototopical drugs: animal modeling. Ann Otol Rhinol Laryngol Suppl 148, 42-45.

Myrzakhanova, M., Gambardella, C., Falugi, C., Gatti, A.M., Tagliafierro, G., Ramoino, P., Bianchini, P., Diaspro, A., 2013. Effects of nanosilver exposure on cholinesterase activities, CD41, and CDF/LIF-like expression in zebrafish (Danio rerio) larvae. Biomed Res Int 2013, 205183.

Ng, A.N., de Jong-Curtain, T.A., Mawdsley, D.J., White, S.J., Shin, J., Appel, B., Dong, P.D., Stainier, D.Y., Heath, J.K., 2005. Formation of the digestive system in zebrafish: III. Intestinal epithelium morphogenesis. Dev Biol 286, 114-135.

Osborne, O.J., Johnston, B.D., Moger, J., Balousha, M., Lead, J.R., Kudoh, T., Tyler, C.R., 2013. Effects of particle size and coating on nanoscale Ag and TiO2 exposure in zebrafish (Danio rerio) embryos. Nanotoxicology 7, 1315-1324.

Ostaszewska, T., Chojnacki, M., Kamaszewski, M., Sawosz-Chwalibog, E., 2016. Histopathological effects of silver and copper nanoparticles on the epidermis, gills, and liver of Siberian sturgeon. Environ Sci Pollut Res Int 23, 1621-1633.

Ou, H.C., Cunningham, L.L., Francis, S.P., Brandon, C.S., Simon, J.A., Raible, D.W., Rubel, E.W., 2009. Identification of FDA-approved drugs and bioactives that protect hair cells in the zebrafish (Danio rerio) lateral line and mouse (Mus musculus) utricle. J Assoc Res Otolaryngol 10, 191-203.

Ou, H.C., Santos, F., Raible, D.W., Simon, J.A., Rubel, E.W., 2010. Drug screening for hearing loss: using the zebrafish lateral line to screen for drugs that prevent and cause hearing loss. Drug Discov Today 15, 265-271.

Powers, C.M., Slotkin, T.A., Seidler, F.J., Badireddy, A.R., Padilla, S., 2011. Silver nanoparticles alter zebrafish development and larval behavior: distinct roles for particle size, coating and composition. Neurotoxicol Teratol 33, 708-714.

Rhouma, M., Beaudry, F., Letellier, A., 2016. Resistance to colistin: what is the fate for this antibiotic in pig production? Int J Antimicrob Agents 48, 119-126.

Sarica, S., Yurttutan, S., 2018. An evaluation of hearing in infants administered with colistin in the premature neonatal intensive care unit. J Matern Fetal Neonatal Med 31, 2918-2922.

Sarkar, B., Verma, S.K., Akhtar, J., Netam, S.P., Gupta, S.K., Panda, P.K., Mukherjee, K., 2018. Molecular aspect of silver nanoparticles regulated embryonic development in Zebrafish (Danio rerio) by Oct-4 expression. Chemosphere 206, 560-567.

Shaw, B.J., Al-Bairuty, G., Handy, R.D., 2012. Effects of waterborne copper nanoparticles and copper sulphate on rainbow trout, (Oncorhynchus mykiss): physiology and accumulation. Aquat Toxicol 116-117, 90-101.

Shen, Y., Yin, W., Liu, D., Shen, J., Wang, Y., 2018. Reply to Cabello et al., "Aquaculture and mcr Colistin Resistance Determinants". mBio 9, e01629-18.

Shih, T.H., Horng, J.L., Hwang, P.P., Lin, L.Y., 2008. Ammonia excretion by the skin of zebrafish (Danio rerio) larvae. Am J Physiol Cell Physiol 295, C1625-1632.

Singer, A.C., Shaw, H., Rhodes, V., Hart, A., 2016. Review of Antimicrobial Resistance in the Environment and Its Relevance to Environmental Regulators. Front Microbiol 7, 1728.

Stewart, W.J., Cardenas, G.S., McHenry, M.J., 2013. Zebrafish larvae evade predators by sensing water flow. The Journal of Experimental Biology 216, 388-398.

Sun, J., Zhang, H., Liu, Y.H., Feng, Y., 2018. Towards Understanding MCR-like Colistin Resistance. Trends Microbiol 26, 794-808.

Sun, Y., Zhang, G., He, Z., Wang, Y., Cui, J., Li, Y., 2016. Effects of copper oxide nanoparticles on developing zebrafish embryos and larvae. Int J Nanomedicine 11, 905-918.

van Aerle, R., Lange, A., Moorhouse, A., Paszkiewicz, K., Ball, K., Johnston, B.D., de-Bastos, E., Booth, T., Tyler, C.R., Santos, E.M., 2013. Molecular mechanisms of toxicity of silver nanoparticles in zebrafish embryos. Environ Sci Technol 47, 8005-8014.

Wang, Y., Tian, G.B., Zhang, R., Shen, Y., Tyrrell, J.M., Huang, X., Zhou, H., Lei, L., Li, H.Y., Doi, Y., Fang, Y., Ren, H., Zhong, L.L., Shen, Z., Zeng, K.J., Wang, S., Liu, J.H., Wu, C., Walsh, T.R., Shen, J., 2017. Prevalence, risk factors, outcomes, and molecular epidemiology of mcr-1-positive Enterobacteriaceae in patients and healthy adults from China: an epidemiological and clinical study. Lancet Infect Dis 17, 390-399.

Wise, R., 2002. Antimicrobial resistance: priorities for action. J Antimicrob Chemother 49, 585-586.

Wu, S.C., Horng, J.L., Liu, S.T., Hwang, P.P., Wen, Z.H., Lin, C.S., Lin, L.Y., 2010a. Ammonium-dependent sodium uptake in mitochondrion-rich cells of medaka (Oryzias latipes) larvae. Am J Physiol Cell Physiol 298, C237-250.

Wu, Y., Zhou, Q., Li, H., Liu, W., Wang, T., Jiang, G., 2010b. Effects of silver nanoparticles on the development and histopathology biomarkers of Japanese medaka (Oryzias latipes) using the partial-life test. Aquat Toxicol 100, 160-167.

Xie, J., Talaska, A.E., Schacht, J., 2011. New developments in aminoglycoside therapy and ototoxicity. Hear Res 281, 28-37.

Xiong, W., Sun, Y., Zhang, T., Ding, X., Li, Y., Wang, M., Zeng, Z., 2015. Antibiotics, Antibiotic Resistance Genes, and Bacterial Community Composition in Fresh Water Aquaculture Environment in China. Microb Ecol 70, 425-432.

Yang, C.W., Chang, Y.T., Chao, W.L., Shiung, II, Lin, H.S., Chen, H., Ho, S.H., Lu, M.J., Lee, P.H., Fan, S.N., 2014. An investigation of total bacterial communities, culturable antibiotic-resistant bacterial communities and integrons in the river water environments of Taipei city. J Hazard Mater 277, 159-168.

Yang, L., Ho, N.Y., Alshut, R., Legradi, J., Weiss, C., Reischl, M., Mikut, R., Liebel, U., Muller, F., Strahle, U., 2009. Zebrafish embryos as models for embryotoxic and teratological effects of chemicals. Reprod Toxicol 28, 245-253.

Yoo, M.H., Rah, Y.C., Choi, J., Park, S., Park, H.C., Oh, K.H., Lee, S.H., Kwon, S.Y., 2016. Embryotoxicity and hair cell toxicity of silver nanoparticles in zebrafish embryos. Int J Pediatr Otorhinolaryngol 83, 168-174. 
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