| 研究生: |
鄭念媛 Nien-Yuan Cheng |
|---|---|
| 論文名稱: |
不同料源製成之市售堆肥其抗生素抗性基因含量調查 Survey of antibiotic resistance gene levels harbored in commercially available composts derived from different feedstock |
| 指導教授: |
林居慶
Chu-Ching Lin |
| 口試委員: | |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 環境工程研究所 Graduate Institute of Environmental Engineering |
| 論文出版年: | 2022 |
| 畢業學年度: | 110 |
| 語文別: | 中文 |
| 論文頁數: | 131 |
| 中文關鍵詞: | 禽畜糞 、堆肥 、抗生素抗藥性基因 、農地土壤 |
| 外文關鍵詞: | manure, compost, antibiotic resistance gene, agriculture soil |
| 相關次數: | 點閱:20 下載:0 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
環保署與農委會近年來大力推動畜牧糞尿資源化政策,建議畜牧業者可不再透過之前的三段式處理,只需經過一般的厭氧消化程序,即可將牧場所產生的畜牧排泄物轉化為沼渣沼液,並當作肥料施用於農地,讓原本該被排放到承受水體而可能造成污染擴散的畜牧糞尿能被「農地農用」,呼應當前的「循環經濟」政策。不過,既有的文獻已指出,傳統的中、常溫厭氧消化處理對於禽畜糞尿所含的抗生素抗性基因(ARG)濃度大多無法有效削減,而ARG濃度在環境持續升高的後果,已被國際權威組織預測將嚴重威脅現代醫學的成就,某種程度暗示著如要推動沼液沼渣作為農地肥分使用的政策時,應先審慎調查確認是否將因此而衍生出土壤環境的抗藥性增長問題。有鑒於ARG的濃度尚未有法規規範,本研究針對行之有年的「堆肥」進行ARG的含量調查,藉此讓沼液沼渣所造成的環境抗生素抗藥性的風險評估有參考對比值。
本研究所選的28件堆肥樣品涵蓋非禽畜糞、牛糞、豬糞、雞糞等不同原料,以基因即時定量技術,定量樣品中的目標基因(包括各個ARG、移動基因元件以及16S rRNA基因),並以統計分析各類樣品彼此之間的相關性與差異性。調查結果顯示: (1)含禽畜糞便的堆肥中抗生素抗藥性基因含量比非禽畜糞的堆肥來的高;(2)不論是非禽畜糞便還是含禽畜糞之堆肥其主要以磺胺類抗生素抗藥性基因以及第一類整合子基因為主;(3)堆肥中的重金屬鋅、銅與抗生素抗藥性基因呈現負相關;(4)堆肥中殘留的抗生素與抗生素抗藥性基因之間是具有相關性;(5)當堆肥進入土壤環境後主要是以四環素類、磺胺類抗生素抗藥性基因以及第一類整合子基因為主;(6)堆肥中的抗生素抗藥性基因及第一類整合子進入土壤環境後,其在環境中的宿命不會因其料源不同而有所差異。這些結果說明不同料源的堆肥中的抗生素抗藥性基因及第一類整合子的豐度確實有所不同,但其對於抗生素耐藥性基因進入環境之影響並不會因為其原料不同而有所差異。此外,對於堆肥中抗生素抗藥性基因及第一類整合子在環境中降解速率值得加以追蹤及確認。
In recent years, the Environmental Protection Agency and the Committee of Agriculture have vigorously promoted the policy of resource utilization of livestock manure and urine, suggesting that livestock farmers can no longer go through the previous three-stage treatment, but only need to go through the general anaerobic digestion process to convert the livestock excrement produced by the pasture. It is used as biogas residue and applied to agricultural land as fertilizer, so that livestock manure that should have been discharged into receiving water bodies and may cause pollution to spread can be used for "farmland agriculture", echoing the current "circular economy" policy. However, the existing literature has pointed out that the traditional anaerobic digestion treatment at room temperature cannot effectively reduce the concentration of antibiotic resistance genes (ARG) contained in livestock manure and urine, and the consequence of the continuous increase of ARG concentration in the environment has been It is predicted by international authoritative organizations that it will seriously threaten the achievements of modern medicine. To some extent, it implies that if we want to promote the policy of using biogas residue as agricultural land fertilizer, we should conduct a careful investigation to confirm whether the drug resistance of the soil environment will be derived from its growth issues. Because the concentration of ARG has not yet been regulated by regulations, this study conducted a survey on the content of ARG in the long-established "compost", to provide a reference and comparative value for the risk assessment of environmental antibiotic resistance caused by biogas slurry and residue.
The 28 compost samples selected in this study covered different raw materials such as non-poultry animal manure, cow manure, pig manure, chicken manure, etc. The target genes (including various ARGs, mobile genetic elements, and 16S rRNA genes) in the samples were quantified by real-time gene quantitative technology, and statistically analyzed the correlation and difference between various samples. The survey results showed that: (1) the content of antibiotic resistance genes in the manure compost was higher than that of the non-manure compost; (2) both non-manure and manure compost mainly contained sulfonamides antibiotic resistance genes and intI1; (3) heavy metals zinc and copper in compost are negatively correlated with antibiotic resistance genes; (4) the residual antibiotics in compost and antibiotic resistance genes are closely related. (5) When the compost enters the soil environment, it is mainly composed of tetracycline and sulfonamide antibiotic resistance genes and intI1; (6) The antibiotic resistance genes and intI1 in compost After entering the soil environment, its fate in the environment will not vary due to different sources. These results indicate that the abundance of antibiotic resistance genes and intI1 in composts from different feedstock are indeed different, but their impact on the entry of antibiotic resistance genes into the environment will not be affected by different raw materials. difference. In addition, the degradation rates of antibiotic resistance genes and intI1 in compost in the environment deserve to be tracked and confirmed.
(1) Cromwell, G. Antimicrobial and promicrobial agents. Swine nutrition 2001.
(2) Mann, A.; Nehra, K.; Rana, J.; Dahiya, T. Antibiotic resistance in agriculture: Perspectives on upcoming strategies to overcome upsurge in resistance. Current Research in Microbial Sciences 2021, 2, 100030.
(3) Ventola, C. L. The Antibiotic Resistance Crisis Part 1: Causes and Threats. Pharmacy and therapeutics 2015, 40 (4), 277.
(4) Kohanski, M. A.; Dwyer, D. J.; Collins, J. J. How antibiotics kill bacteria: from targets to networks. Nature Reviews Microbiology 2010, 8 (6), 423-435. DOI: 10.1038/nrmicro2333.
(5) Mann, J. Antibiotics: Actions, Origins, Resistance. Natural Product Reports 2005, 22 (2), 304. DOI: 10.1039/b417591n.
(6) Espeli, O.; Marians, K. J. Untangling intracellular DNA topology. Molecular Microbiology 2004, 52 (4), 925-931. DOI: 10.1111/j.1365-2958.2004.04047.x.
(7) Ayoub Moubareck, C. Polymyxins and Bacterial Membranes: A Review of Antibacterial Activity and Mechanisms of Resistance. Membranes 2020, 10 (8), 181. DOI: 10.3390/membranes10080181.
(8) Epand, R. M.; Walker, C.; Epand, R. F.; Magarvey, N. A. Molecular mechanisms of membrane targeting antibiotics. Biochimica et Biophysica Acta (BBA) - Biomembranes 2016, 1858 (5), 980-987. DOI: https://doi.org/10.1016/j.bbamem.2015.10.018.
(9) KONG, K. F.; Schneper, L.; Mathee, K. Beta‐lactam antibiotics: from antibiosis to resistance and bacteriology. Apmis 2010, 118 (1), 1-36.
(10) Fernández, V.; Aguilar; Rojo. Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications. International Journal of Molecular Sciences 2019, 20 (20), 4996. DOI: 10.3390/ijms20204996.
(11) Allen, H. K.; Donato, J.; Wang, H. H.; Cloud-Hansen, K. A.; Davies, J.; Handelsman, J. Call of the wild: antibiotic resistance genes in natural environments. Nature Reviews Microbiology 2010, 8 (4), 251-259. Blair, J. M. A.; Webber, M. A.; Baylay, A. J.; Ogbolu, D. O.; Piddock, L. J. V. Molecular mechanisms of antibiotic resistance. Nature Reviews Microbiology 2015, 13 (1), 42-51. DOI: 10.1038/nrmicro3380.
(12) Chee-Sanford, J. C.; Mackie, R. I.; Koike, S.; Krapac, I. G.; Lin, Y.-F.; Yannarell, A. C.; Maxwell, S.; Aminov, R. I. Fate and Transport of Antibiotic Residues and Antibiotic Resistance Genes following Land Application of Manure Waste. Journal of Environmental Quality 2009, 38 (3), 1086-1108. DOI: 10.2134/jeq2008.0128.
(13) Choi, U.; Lee, C.-R. Distinct Roles of Outer Membrane Porins in Antibiotic Resistance and Membrane Integrity in Escherichia coli. Frontiers in Microbiology 2019, 10, Original Research. DOI: 10.3389/fmicb.2019.00953.
(14) Delmar, J. A.; Su, C.-C.; Yu, E. W. Bacterial Multidrug Efflux Transporters. Annual Review of Biophysics 2014, 43 (1), 93-117. DOI: 10.1146/annurev-biophys-051013-022855.
(15) Webber, M. A.; Piddock, L. J. V. The importance of efflux pumps in bacterial antibiotic resistance. Journal of Antimicrobial Chemotherapy 2003, 51 (1), 9-11. DOI: 10.1093/jac/dkg050 (acccessed 6/17/2022).
(16) Nikaido, H. Multidrug resistance in bacteria. Annu Rev Biochem 2009, 78, 119-146. DOI: 10.1146/annurev.biochem.78.082907.145923.
(17) Khan, S. N.; Khan, A. U. Breaking the spell: combating multidrug resistant ‘superbugs’. Frontiers in microbiology 2016, 7, 174.
(18) Schwartz, T.; Kohnen, W.; Jansen, B.; Obst, U. Detection of antibiotic-resistant bacteria and their resistance genes in wastewater, surface water, and drinking water bio¢lms. FEMS Microbiology Ecology 2003, 43 (3), 325-335.
(19) Chee‐Sanford, J. C.; Mackie, R. I.; Koike, S.; Krapac, I. G.; Lin, Y. F.; Yannarell, A. C.; Maxwell, S.; Aminov, R. I. Fate and transport of antibiotic residues and antibiotic resistance genes following land application of manure waste. Journal of environmental quality 2009, 38 (3), 1086-1108.
(20) Jernberg, C.; Löfmark, S.; Edlund, C.; Jansson, J. K. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology 2010, 156 (11), 3216-3223.
(21) Andremont, A. Commensal flora may play key role in spreading antibiotic resistance. Asm News 2003, 69 (12), 601-607.
(22) Organization, W. H. Antimicrobial resistance: global report on surveillance; World Health Organization, 2014.
(23) Dodd, M. C. Potential impacts of disinfection processes on elimination and deactivation of antibiotic resistance genes during water and wastewater treatment. Journal of Environmental Monitoring 2012, 14 (7), 1754. DOI: 10.1039/c2em00006g.
(24) Davison, J. Genetic exchange between bacteria in the environment. Plasmid 1999, 42 (2), 73-91.
(25) Vikesland, P. J.; Pruden, A.; Alvarez, P. J. J.; Aga, D.; Burgmann, H.; Li, X. D.; Manaia, C. M.; Nambi, I.; Wigginton, K.; Zhang, T.; et al. Toward a Comprehensive Strategy to Mitigate Dissemination of Environmental Sources of Antibiotic Resistance. Environ Sci Technol 2017, 51 (22), 13061-13069. DOI: 10.1021/acs.est.7b03623.
(26) Ben, W.; Wang, J.; Cao, R.; Yang, M.; Zhang, Y.; Qiang, Z. Distribution of antibiotic resistance in the effluents of ten municipal wastewater treatment plants in China and the effect of treatment processes. Chemosphere 2017, 172, 392-398.
(27) LaPara, T. M.; Burch, T. R.; McNamara, P. J.; Tan, D. T.; Yan, M.; Eichmiller, J. J. Tertiary-treated municipal wastewater is a significant point source of antibiotic resistance genes into Duluth-Superior Harbor. Environmental science & technology 2011, 45 (22), 9543-9549.
(28) Zhu, Y.-G.; Johnson, T. A.; Su, J.-Q.; Qiao, M.; Guo, G.-X.; Stedtfeld, R. D.; Hashsham, S. A.; Tiedje, J. M. Diverse and abundant antibiotic resistance genes in Chinese swine farms. Proceedings of the National Academy of Sciences 2013, 110 (9), 3435-3440. DOI: 10.1073/pnas.1222743110.
(29) Echeverria-Palencia, C. M.; Thulsiraj, V.; Tran, N.; Ericksen, C. A.; Melendez, I.; Sanchez, M. G.; Walpert, D.; Yuan, T.; Ficara, E.; Senthilkumar, N.; et al. Disparate Antibiotic Resistance Gene Quantities Revealed across 4 Major Cities in California: A Survey in Drinking Water, Air, and Soil at 24 Public Parks. ACS Omega 2017, 2 (5), 2255-2263. DOI: 10.1021/acsomega.7b00118.
(30) Pei, R.; Kim, S.-C.; Carlson, K. H.; Pruden, A. Effect of river landscape on the sediment concentrations of antibiotics and corresponding antibiotic resistance genes (ARG). Water research 2006, 40 (12), 2427-2435.
(31) 簡妤儒. 抗生素的用與禁--台灣養雞業和養豬業的產業結構與用藥邏輯. 科技部補助專題研究計畫成果報告 2016.
(32) Xie, W. Y.; Shen, Q.; Zhao, F. Antibiotics and antibiotic resistance from animal manures to soil: a review. European journal of soil science 2018, 69 (1), 181-195.
(33) Bao, Y.; Zhou, Q.; Guan, L.; Wang, Y. Depletion of chlortetracycline during composting of aged and spiked manures. Waste Manag 2009, 29 (4), 1416-1423. DOI: 10.1016/j.wasman.2008.08.022.
(34) Schwartz, T.; Kohnen, W.; Jansen, B.; Obst, U. Detection of antibiotic-resistant bacteria and their resistance genes in wastewater, surface water, and drinking water biofilms. FEMS microbiology ecology 2003, 43 (3), 325-335.
(35) Knapp, C. W.; Dolfing, J.; Ehlert, P. A.; Graham, D. W. Evidence of Increasing Antibiotic Resistance Gene Abundances in Archived Soils since 1940. Environmental science & technology 2010, 44 (2), 580-587.
(36) Anadón, A. WS14 The EU ban of antibiotics as feed additives (2006): alternatives and consumer safety. Journal of Veterinary Pharmacology and Therapeutics 2006, 29, 41-44.
(37) Van Boeckel, T. P.; Brower, C.; Gilbert, M.; Grenfell, B. T.; Levin, S. A.; Robinson, T. P.; Teillant, A.; Laxminarayan, R. Global trends in antimicrobial use in food animals. Proc Natl Acad Sci U S A 2015, 112 (18), 5649-5654. DOI: 10.1073/pnas.1503141112.
(38) 程梅萍; 蕭庭訓; 廖仁寶. 豬糞尿和廢水中抗生素與四環素抗性基因流布研究. 畜產研究 2018, 51 (1), 39-51.
(39) Zalewska, M.; Błażejewska, A.; Czapko, A.; Popowska, M. Antibiotics and Antibiotic Resistance Genes in Animal Manure – Consequences of Its Application in Agriculture. Frontiers in Microbiology 2021, 12, Review. DOI: 10.3389/fmicb.2021.610656.
(40) Yang, Q.; Tian, T.; Niu, T.; Wang, P. Molecular characterization of antibiotic resistance in cultivable multidrug-resistant bacteria from livestock manure. Environ Pollut 2017, 229, 188-198. DOI: 10.1016/j.envpol.2017.05.073.
(41) Heuer, H.; Schmitt, H.; Smalla, K. Antibiotic resistance gene spread due to manure application on agricultural fields. Current opinion in microbiology 2011, 14 (3), 236-243.
(42) 陳明晉; 廖秋榮; 蔡宜峰. 堆肥技術與設備手冊及案例彙編. 經濟部工業局, 財團法人台灣綠色生產力基金會 2005.
(43) Zhou, Z.; Yao, H. Effects of Composting Different Types of Organic Fertilizer on the Microbial Community Structure and Antibiotic Resistance Genes. Microorganisms 2020, 8 (2), 268. DOI: 10.3390/microorganisms8020268.
(44) Mitchell, S. M.; Ullman, J. L.; Bary, A.; Cogger, C. G.; Teel, A. L.; Watts, R. J. Antibiotic degradation during thermophilic composting. Water, Air, Soil Pollut. 2015, 226, 13.
(45) Youngquist, C. P.; Mitchell, S. M.; Cogger, C. G. Fate of antibiotics and antibiotic resistance during digestion and composting: a review. Journal of Environmental Quality 2016, 45 (2), 537-545.
(46) Sun, W.; Qian, X.; Gu, J.; Wang, X.-J.; Duan, M.-L. Mechanism and Effect of Temperature on Variations in Antibiotic Resistance Genes during Anaerobic Digestion of Dairy Manure. Scientific Reports 2016, 6 (1), 30237. DOI: 10.1038/srep30237.
(47) Oliver, J. P.; Gooch, C. A.; Lansing, S.; Schueler, J.; Hurst, J. J.; Sassoubre, L.; Crossette, E. M.; Aga, D. S. Invited review: Fate of antibiotic residues, antibiotic-resistant bacteria, and antibiotic resistance genes in US dairy manure management systems. Journal of Dairy Science 2020, 103 (2), 1051-1071. DOI: 10.3168/jds.2019-16778.
(48) Xie, W. Y.; Yang, X. P.; Li, Q.; Wu, L. H.; Shen, Q. R.; Zhao, F. J. Changes in antibiotic concentrations and antibiotic resistome during commercial composting of animal manures. Environ Pollut 2016, 219, 182-190. DOI: 10.1016/j.envpol.2016.10.044.
(49) Qian, X.; Gu, J.; Sun, W.; Wang, X. J.; Su, J. Q.; Stedfeld, R. Diversity, abundance, and persistence of antibiotic resistance genes in various types of animal manure following industrial composting. J Hazard Mater 2018, 344, 716-722. DOI: 10.1016/j.jhazmat.2017.11.020.
(50) D’Costa, V. M.; King, C. E.; Kalan, L.; Morar, M.; Sung, W. W.; Schwarz, C.; Froese, D.; Zazula, G.; Calmels, F.; Debruyne, R. Antibiotic resistance is ancient. Nature 2011, 477 (7365), 457-461.
(51) Barka, E. A.; Vatsa, P.; Sanchez, L.; Gaveau-Vaillant, N.; Jacquard, C.; Klenk, H.-P.; Clément, C.; Ouhdouch, Y.; Wezel, G. P. v. Taxonomy, Physiology, and Natural Products of Actinobacteria. Microbiology and Molecular Biology Reviews 2016, 80 (1), 1-43. DOI: doi:10.1128/MMBR.00019-15.
(52) Chen, Q.; An, X.; Li, H.; Su, J.; Ma, Y.; Zhu, Y. G. Long-term field application of sewage sludge increases the abundance of antibiotic resistance genes in soil. Environ Int 2016, 92-93, 1-10. DOI: 10.1016/j.envint.2016.03.026.
(53) Wei, Z.; Shen, W.; Feng, K.; Feng, Y.; He, Z.; Li, Y.; Jiang, C.; Liu, S.; Zhu, Y.-G.; Deng, Y. Organic fertilizer potentiates the transfer of typical antibiotic resistance gene among special bacterial species. Journal of Hazardous Materials 2022, 435, 128985. DOI: https://doi.org/10.1016/j.jhazmat.2022.128985.
(54) Zhang, Y. J.; Hu, H. W.; Gou, M.; Wang, J. T.; Chen, D.; He, J. Z. Temporal succession of soil antibiotic resistance genes following application of swine, cattle and poultry manures spiked with or without antibiotics. Environ Pollut 2017, 231 (Pt 2), 1621-1632. DOI: 10.1016/j.envpol.2017.09.074.
(55) Li, J.; Xin, Z.; Zhang, Y.; Chen, J.; Yan, J.; Li, H.; Hu, H. Long-term manure application increased the levels of antibiotics and antibiotic resistance genes in a greenhouse soil. Applied Soil Ecology 2017, 121, 193-200. DOI: 10.1016/j.apsoil.2017.10.007.
(56) Zhang, Y. J.; Hu, H. W.; Chen, Q. L.; Singh, B. K.; Yan, H.; Chen, D.; He, J. Z. Transfer of antibiotic resistance from manure-amended soils to vegetable microbiomes. Environ Int 2019, 130, 104912. DOI: 10.1016/j.envint.2019.104912.
(57) Michael, C. A.; Dominey-Howes, D.; Labbate, M. The Antimicrobial Resistance Crisis: Causes, Consequences, and Management. Frontiers in Public Health 2014, 2, Review. DOI: 10.3389/fpubh.2014.00145.
(58) Domingues, S.; da Silva, G. J.; Nielsen, K. M. Global dissemination patterns of common gene cassette arrays in class 1 integrons. Microbiology 2015, 161 (7), 1313-1337. DOI: https://doi.org/10.1099/mic.0.000099.
(59) Gillings, M. R. Class 1 integrons as invasive species. Current Opinion in Microbiology 2017, 38, 10-15. DOI: https://doi.org/10.1016/j.mib.2017.03.002.
(60) Burch, T. R.; Sadowsky, M. J.; Lapara, T. M. Fate of Antibiotic Resistance Genes and Class 1 Integrons in Soil Microcosms Following the Application of Treated Residual Municipal Wastewater Solids. Environmental Science & Technology 2014, 48 (10), 5620-5627. DOI: 10.1021/es501098g.
(61) Gillings, M. R.; Gaze, W. H.; Pruden, A.; Smalla, K.; Tiedje, J. M.; Zhu, Y. G. Using the class 1 integron-integrase gene as a proxy for anthropogenic pollution. ISME J 2015, 9 (6), 1269-1279. DOI: 10.1038/ismej.2014.226.
(62) Lacotte, Y.; Ploy, M.-C.; Raherison, S. Class 1 integrons are low-cost structures in Escherichia coli. The ISME Journal 2017, 11 (7), 1535-1544. DOI: 10.1038/ismej.2017.38.
(63) Palencia, C. M. E. Distribution, Emergence, Fate and Transport of Antibiotic Resistance Genes in Environmental Compartments: Studies at the Nexus of Human-Environment Interaction; University of California, Los Angeles, 2018.
(64) Zhou, X.; Qiao, M.; Su, J.-Q.; Zhu, Y.-G. High-throughput characterization of antibiotic resistome in soil amended with commercial organic fertilizers. Journal of Soils and Sediments 2019, 19 (2), 641-651. DOI: 10.1007/s11368-018-2064-6.
(65) Carter, L. J.; Harris, E.; Williams, M.; Ryan, J. J.; Kookana, R. S.; Boxall, A. B. A. Fate and Uptake of Pharmaceuticals in Soil–Plant Systems. Journal of Agricultural and Food Chemistry 2014, 62 (4), 816-825. DOI: 10.1021/jf404282y.
(66) Ng, L.-K.; Martin, I.; Alfa, M.; Mulvey, M. Multiplex PCR for the detection of tetracycline resistant genes. Molecular and cellular probes 2001, 15 (4), 209-215.
(67) Aminov, R.; Garrigues-Jeanjean, N.; Mackie, R. Molecular ecology of tetracycline resistance: development and validation of primers for detection of tetracycline resistance genes encoding ribosomal protection proteins. Applied and environmental microbiology 2001, 67 (1), 22-32.
(68) Marti, E.; Jofre, J.; Balcazar, J. L. Prevalence of antibiotic resistance genes and bacterial community composition in a river influenced by a wastewater treatment plant. PloS one 2013, 8 (10), e78906.
(69) Xi, C.; Zhang, Y.; Marrs, C. F.; Ye, W.; Simon, C.; Foxman, B.; Nriagu, J. Prevalence of antibiotic resistance in drinking water treatment and distribution systems. Applied and environmental microbiology 2009, 75 (17), 5714-5718.
(70) Alexander, J.; Bollmann, A.; Seitz, W.; Schwartz, T. Microbiological characterization of aquatic microbiomes targeting taxonomical marker genes and antibiotic resistance genes of opportunistic bacteria. Science of the Total Environment 2015, 512, 316-325.
(71) Chen, J.; Yu, Z.; Michel Jr, F. C.; Wittum, T.; Morrison, M. Development and application of real-time PCR assays for quantification of erm genes conferring resistance to macrolides-lincosamides-streptogramin B in livestock manure and manure management systems. Applied and environmental microbiology 2007, 73 (14), 4407-4416.
(72) Luo, Y.; Mao, D.; Rysz, M.; Zhou, Q.; Zhang, H.; Xu, L.; JJ Alvarez, P. Trends in Antibiotic Resistance Genes Occurrence in the Haihe River, China. Environmental science & technology 2010, 44 (19), 7220-7225.
(73) Deng, J.-Y. 重金屬生物有效性對於抗生素抗性基因在農地土壤的分佈與持續之影響. National Central University, 2018. Chang, C.-S. 抗生素抗性菌與抗性基因在污水處理程序中的動態變化. National Central University, 2019.
(74) Deng, W.; Wang, Y.; Liu, Z.; Cheng, H.; Xue, Y. HemI: A Toolkit for Illustrating Heatmaps. PLoS ONE 2014, 9 (11), e111988. DOI: 10.1371/journal.pone.0111988.
(75) 陳炳良. 有機堆肥施用對土壤性質之影響. 國立屏東科技大學, 2003. 陳尊賢. 長期施用豬糞堆肥對土壤中重金屬之累積及合理施用量之評估. 農業試驗所特刊第 50 號 1995.
(76) Gondek, M.; Weindorf, D. C.; Thiel, C.; Kleinheinz, G. Soluble Salts in Compost and Their Effects on Soil and Plants: A Review. Compost Science & Utilization 2020, 28 (2), 59-75. DOI: 10.1080/1065657x.2020.1772906.
(77) 林浩潭. 第四章 施肥與土壤鹽分累積; 行政院農業委員會農業藥物毒物試驗所.
(78) Chang, E.-H.; Chung, R.-S.; Tsai, Y.-H. Effect of different application rates of organic fertilizer on soil enzyme activity and microbial population. Soil Science and Plant Nutrition 2007, 53 (2), 132-140. DOI: 10.1111/j.1747-0765.2007.00122.x.
(79) Rutherford, D.; Bednar, A.; Garbarino, J.; Needham, R.; Staver, K.; Wershaw, R. Environmental Fate of Roxarsone in Poultry Litter. Part II. Mobility of Arsenic in Soils Amended with Poultry Litter. Environmental science & technology 2003, 37 (8), 1515-1520.
(80) Mandal, B. K.; Suzuki, K. T. Arsenic round the world: a review. Talanta 2002, 58 (1), 201-235.
(81) Xie, W.-Y.; Wang, Y.-T.; Yuan, J.; Hong, W.-D.; Niu, G.-Q.; Zou, X.; Yang, X.-P.; Shen, Q.; Zhao, F.-J. Prevalent and highly mobile antibiotic resistance genes in commercial organic fertilizers. Environment International 2022, 162, 107157. DOI: https://doi.org/10.1016/j.envint.2022.107157.
(82) Wang, Q.; Guo, M.; Yates, S. R. Degradation kinetics of manure-derived sulfadimethoxine in amended soil. Journal of agricultural and food chemistry 2006, 54 (1), 157-163.
(83) Kay, P.; Blackwell, P. A.; Boxall, A. B. Fate of veterinary antibiotics in a macroporous tile drained clay soil. Environmental Toxicology and Chemistry: An International Journal 2004, 23 (5), 1136-1144.
(84) Dolliver, H.; Gupta, S.; Noll, S. Antibiotic Degradation during Manure Composting. Journal of Environmental Quality 2008, 37 (3), 1245-1253. DOI: 10.2134/jeq2007.0399.
(85) Chang, Q.; Wang, W.; Regev‐Yochay, G.; Lipsitch, M.; Hanage, W. P. Antibiotics in agriculture and the risk to human health: how worried should we be? Evolutionary Applications 2015, 8 (3), 240-247. DOI: 10.1111/eva.12185.
(86) Min Jang, H.; Choi, S.; Shin, J.; Kan, E.; Mo Kim, Y. Additional reduction of antibiotic resistance genes and human bacterial pathogens via thermophilic aerobic digestion of anaerobically digested sludge. Bioresource Technology 2019, 273, 259-268. DOI: https://doi.org/10.1016/j.biortech.2018.11.027.
(87) He, Y.; Yuan, Q.; Mathieu, J.; Stadler, L.; Senehi, N.; Sun, R.; Alvarez, P. J. J. Antibiotic resistance genes from livestock waste: occurrence, dissemination, and treatment. npj Clean Water 2020, 3 (1). DOI: 10.1038/s41545-020-0051-0.
(88) Organization, W. H. WHO global strategy for containment of antimicrobial resistance; World Health Organization, 2001.
(89) Zhang, M.; He, L. Y.; Liu, Y. S.; Zhao, J. L.; Liu, W. R.; Zhang, J. N.; Chen, J.; He, L. K.; Zhang, Q. Q.; Ying, G. G. Fate of veterinary antibiotics during animal manure composting. Sci Total Environ 2019, 650 (Pt 1), 1363-1370. DOI: 10.1016/j.scitotenv.2018.09.147.
(90) Riaz, L.; Wang, Q.; Yang, Q.; Li, X.; Yuan, W. Potential of industrial composting and anaerobic digestion for the removal of antibiotics, antibiotic resistance genes and heavy metals from chicken manure. Sci Total Environ 2020, 718, 137414. DOI: 10.1016/j.scitotenv.2020.137414.
(91) Diehl, D. L.; LaPara, T. M. Effect of temperature on the fate of genes encoding tetracycline resistance and the integrase of class 1 integrons within anaerobic and aerobic digesters treating municipal wastewater solids. Environ. Sci. Technol. 2010, 44 (23), 9128.
(92) Xu, M.; Stedtfeld, R. D.; Wang, F.; Hashsham, S. A.; Song, Y.; Chuang, Y.; Fan, J.; Li, H.; Jiang, X.; Tiedje, J. M. Composting increased persistence of manure-borne antibiotic resistance genes in soils with different fertilization history. Sci Total Environ 2019, 689, 1172-1180. DOI: 10.1016/j.scitotenv.2019.06.376.
(93) Lin, H.; Chapman, S. J.; Freitag, T. E.; Kyle, C.; Ma, J.; Yang, Y.; Zhang, Z. Fate of tetracycline and sulfonamide resistance genes in a grassland soil amended with different organic fertilizers. Ecotoxicol Environ Saf 2019, 170, 39-46. DOI: 10.1016/j.ecoenv.2018.11.059.
(94) 林居慶; 陳?如. 商業有機肥料與沼渣沼液作為環境抗生素抗藥性發展的潛在來源探究; Commercially available organic fertilizers and anaerobic digestion residues as the potential source of antibiotic resistance development in the environment. 2020.
(95) Cao, Y.; Zhao, J.; Wang, Q.; Bai, S.; Yang, Q.; Wei, Y.; Wang, R. Industrial aerobic composting and the addition of microbial agents largely reduce the risks of heavy metal and ARG transfer through livestock manure. Ecotoxicology and Environmental Safety 2022, 239, 113694. DOI: https://doi.org/10.1016/j.ecoenv.2022.113694.
(96) Deng, W.; Zhang, A.; Chen, S.; He, X.; Jin, L.; Yu, X.; Yang, S.; Li, B.; Fan, L.; Ji, L.; et al. Heavy metals, antibiotics and nutrients affect the bacterial community and resistance genes in chicken manure composting and fertilized soil. Journal of Environmental Management 2020, 257, 109980. DOI: https://doi.org/10.1016/j.jenvman.2019.109980.
(97) Zhang, M.; He, L.-Y.; Liu, Y.-S.; Zhao, J.-L.; Zhang, J.-N.; Chen, J.; Zhang, Q.-Q.; Ying, G.-G. Variation of antibiotic resistome during commercial livestock manure composting. Environment International 2020, 136, 105458. DOI: https://doi.org/10.1016/j.envint.2020.105458.
(98) Seiler, C.; Berendonk, T. U. Heavy metal driven co-selection of antibiotic resistance in soil and water bodies impacted by agriculture and aquaculture. Front Microbiol 2012, 3, 399. DOI: 10.3389/fmicb.2012.00399.