人体肠道耐药基因组的研究进展
Advances in Human Gut Resistome
-
摘要: 人类肠道菌群是耐药基因（antibiotic resistance genes，ARGs）的"储存库"，且与人体健康密切相关。目前，抗生素的滥用严重，进一步加剧了耐药基因的传播和扩散。细菌耐药问题严重影响人体健康、食品安全和生态安全，携带耐药基因的致病菌对临床治疗造成巨大威胁。本文结合国内外研究进展，在总结人体肠道耐药基因组研究方法的基础上，探讨了肠道耐药基因的组成、来源、传播和进化，并对未来研究进行了展望，旨在促进公众对肠道耐药基因的认知，并为抗生素的合理使用提供理论支持。Abstract: Human gut microbiota is the reservoir of antibiotic resistance genes (ARGs) and it plays an important role to human health. The abuse of antibiotics is still severe at present, which further aggravates the spread of ARGs. Bacterial resistance seriously affects human health, food safety and ecological safety, and pathogens carrying ARGs pose a great threat to clinical treatment. In combination with the research progress in China and abroad, this paper discussed in detail about gut resistome from the aspects including the composition, origin, propagation and evolution. In addition, the research methods of human gut resistome and the future prospect were summarized. This study could promote the public’s understanding of gut resistome and provide theoretical support for rational use of antibiotics.
-
Key words:
- antibiotics /
- antibiotic resistance genes /
- gut microbiota /
- horizontal gene transfer
-
-
Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing[J]. Nature, 2010, 464(7285):59-65 郭慧玲, 邵玉宇, 孟和毕力格, 等. 肠道菌群与疾病关系的研究进展[J]. 微生物学通报, 2015, 42(2):400-410 Guo H L, Shao Y Y, Menghe B, et al. Research on the relation between gastrointestinal microbiota and disease[J]. Microbiology China, 2015, 42(2):400-410(in Chinese)
杨凤霞, 毛大庆, 罗义, 等. 环境中抗生素抗性基因的水平传播扩散[J]. 应用生态学报, 2013, 24(10):2993-3002 Yang F X, Mao D Q, Luo Y, et al. Horizontal transfer of antibiotic resistance genes in the environment[J].Chinese Journal of Applied Ecology, 2013, 24(10):2993-3002(in Chinese)
Allen H K, Donato J, Wang H H, et al. Call of the wild:Antibiotic resistance genes in natural environments[J]. Nature Reviews Microbiology, 2010, 8(4):251-259 Martinez J. Natural antibiotic resistance and contamination by antibiotic resistance determinants:The two ages in the evolution of resistance to antimicrobials[J]. Frontiers in Microbiology, 2012, 3(1):1 Cant ón R. Antibiotic resistance genes from the environment:A perspective through newly identified antibiotic resistance mechanisms in the clinical setting[J]. Clinical Microbiology and Infection, 2009, 15(s1):20-25 Wright G D. The antibiotic resistome:The nexus of chemical and genetic diversity[J]. Nature Reviews Microbiology, 2007, 5(3):175-186 李显志. 抗生素耐药基因古老起源与现代进化及其警示[J]. 中国抗生素杂志, 2013, 38(2):81-89 Li X Z. Ancient origin and modern evolution of antibiotic resistome and their implications[J]. Chinese Journal of Antibiotics, 2013, 38(2):81-89(in Chinese)
Hu Y, Yang X, Qin J, et al. Metagenome-wide analysis of antibiotic resistance genes in a large cohort of human gut microbiota[J]. Nature Communications, 2013, 4:2151 Salyers A A, Gupta A, Wang Y. Human intestinal bacteria as reservoirs for antibiotic resistance genes[J]. Trends in Microbiology, 2004, 12(9):412-416 Baron S A, Diene S M, Rolain J M. Human microbiomes and antibiotic resistance[J]. Human Microbiome Journal, 2018, 10:43-52 Lagier J C, Dubourg G, Million M, et al. Culturing the human microbiota and culturomics[J]. Nature Reviews Microbiology, 2018, 16:540-550 Van Schaik W. The human gut resistome[J]. Philosophical Transactions of the Royal Society of London Series B, Biological Sciences, 2015, 370(1670):doi.org/10.1098/rstb.2014.0087 Mcarthur A G, Waglechner N, Nizam F, et al. The comprehensive antibiotic resistance database[J]. Antimicrobial Agents and Chemotherapy, 2013, 57(7):3348-3357 Liu B, Pop M. ARDB-Antibiotic resistance genes database[J]. Nucleic Acids Research, 2008, 37(suppl_1):D443-D447 Zhou C E, Smith J, Lam M, et al. MvirDB-A microbial database of protein toxins, virulence factors and antibiotic resistance genes for bio-defence applications[J]. Nucleic Acids Research, 2006, 35(suppl_1):D391-D394 Scaria J, Chandramouli U, Verma S K. Antibiotic resistance genes online (ARGO):A database on vancomycin and beta-lactam resistance genes[J]. Bioinformation, 2005, 1(1):5-7 Kleinheinz K A, Joensen K G, Larsen M V. Applying the ResFinder and VirulenceFinder web-services for easy identification of acquired antibiotic resistance and E. coli virulence genes in bacteriophage and prophage nucleotide sequences[J]. Bacteriophage, 2014, 4(2):e27943 Gibson M K, Forsberg K J, Dantas G. Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology[J]. The ISME Journal, 2015, 9(1):207-216 Gupta S K, Padmanabhan B R, Diene S M, et al. ARG-ANNOT, a new bioinformatic tool to discover antibiotic resistance genes in bacterial genomes[J]. Antimicrobial Agents and Chemotherapy, 2014, 58(1):212-220 Li L G, Yin X, Zhang T. Tracking antibiotic resistance gene pollution from different sources using machine-learning classification[J]. Microbiome, 2018, 6(1):93 Ufarté L, Potocki-Veronese G, Laville É. Discovery of new protein families and functions:New challenges in functional metagenomics for biotechnologies and microbial ecology[J]. Frontiers in Microbiology, 2015, 6:563 Verastegui Y, Cheng J, Engel K, et al. Multisubstrate isotope labeling and metagenomic analysis of active soil bacterial communities[J]. mBio, 2014, 5(4):e01157-14 王淑娴, 刁菁, 樊英, 等. MALDI-TOF MS技术用于细菌鉴定的研究进展[J]. 农业灾害研究, 2019, 9(5):20-23 Wang S X, Diao J, Fan Y, et al. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for bacterial srain identification[J]. Journal of Agricultural Catastrophology, 2019, 9(5):20-23(in Chinese)
Yatsunenko T, Rey F E, Manary M J, et al. Human gut microbiome viewed across age and geography[J]. Nature, 2012, 486:222-227 Lu N, Hu Y, Zhu L, et al. DNA microarray analysis reveals that antibiotic resistance-gene diversity in human gut microbiota is age related[J]. Scientific Reports, 2014, 4(1):4302 Ruppé E, Ghozlane A, Tap J, et al. Prediction of the intestinal resistome by a three-dimensional structure-based method[J]. Nature Microbiology, 2019, 4(1):112-123 Feng J, Li B, Jiang X, et al. Antibiotic resistome in a large-scale healthy human gut microbiota deciphered by metagenomic and network analyses[J]. Environmental Microbiology, 2018, 20(1):355-368 Duan Y, Chen Z, Tan L, et al. Gut resistomes, microbiota and antibiotic residues in Chinese patients undergoing antibiotic administration and healthy individuals[J]. The Science of the Total Environment, 2019, 705:135674 Scott K P, Melville C M, Barbosa T M, et al. Occurrence of the new tetracycline resistance gene tet (W) in bacteria from the human gut[J]. Antimicrobial Agents and Chemotherapy, 2000, 44(3):775-777 Moore A M, Ahmadi S, Patel S, et al. Gut resistome development in healthy twin pairs in the first year of life[J]. Microbiome, 2015, 3(1):27 Bäckhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life[J]. Cell Host & Microbe, 2015, 17(5):690-703 Vangay P, Ward T, Gerber Jeffrey S, et al. Antibiotics, pediatric dysbiosis, and disease[J]. Cell Host & Microbe, 2015, 17(5):553-564 Palleja A, Mikkelsen K H, Forslund S K, et al. Recovery of gut microbiota of healthy adults following antibiotic exposure[J]. Nature Microbiology, 2018, 3(11):1255-1265 Raymond F, Ouameur A A, Déraspe M, et al. The initial state of the human gut microbiome determines its reshaping by antibiotics[J]. The ISME Journal, 2015, 10:707-720 Li J, Rettedal E A, van der Helm E, et al. Antibiotic treatment drives the diversification of the human gut resistome[J]. Genomics, Proteomics & Bioinformatics, 2019, 17(1):39-51 Forslund K, Sunagawa S, Roat Kultima J, et al. Country-specific antibiotic use practices impact the human gut resistome[J]. Genome Research, 2013, 23(7):1163-1169 Maier L, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on human gut bacteria[J]. Nature, 2018, 555(7698):623 Wang Y, Lu J, Mao L, et al. Antiepileptic drug carbamazepine promotes horizontal transfer of plasmid-borne multi-antibiotic resistance genes within and across bacterial genera[J]. The ISME Journal, 2019, 13(2):509-522 Lu J, Jin M, Nguyen S H, et al. Non-antibiotic antimicrobial triclosan induces multiple antibiotic resistance through genetic mutation[J]. Environment International, 2018, 118:257-265 Häsler R, Kautz C, Rehman A, et al. The antibiotic resistome and microbiota landscape of refugees from Syria, Iraq and Afghanistan in Germany[J]. Microbiome, 2018, 6(1):37 Smits S A, Leach J, Sonnenburg E D, et al. Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania[J]. Science, 2017, 357(6353):802-806 Pehrsson E C, Tsukayama P, Patel S, et al. Interconnected microbiomes and resistomes in low-income human habitats[J]. Nature, 2016, 533(7602):212 Pal C, Bengtsson-Palme J, Kristiansson E, et al. The structure and diversity of human, animal and environmental resistomes[J]. Microbiome, 2016, 4(1):54 Xie J, Jin L, Luo X, et al. Seasonal disparities in airborne bacteria and associated antibiotic resistance genes in PM2.5 between urban and rural sites[J]. Environmental Science & Technology Letters, 2018, 5(2):74-79 Liu Y Y, Wang Y, Walsh T R, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China:A microbiological and molecular biological study[J]. The Lancet Infectious Diseases, 2016, 16(2):161-168 Ma L, Li B, Jiang X T, et al. Catalogue of antibiotic resistome and host-tracking in drinking water deciphered by a large scale survey[J]. Microbiome, 2017, 5(1):154 李林云, 谭璐, 崔玉晓, 等. 饮用水中细菌耐药及其健康风险研究进展[J]. 生态毒理学报, 2018, 13(2):2-12 Li L Y, Tan L, Cui Y X, et al. Bacterial resistance and human health risk in drinking water[J]. Asian Journal of Ecotoxicology, 2018, 13(2):2-12(in Chinese)
盛嫣然, 朱晓勇. 母-胎肠道内微生物群落以及母-胎微生物传输的研究进展[J]. 中华生殖与避孕杂志, 2017, 37(9):773-778 Sheng Y R, Zhu X Y. Research progress on the maternal-fetal intestinal microbiome and maternal-fetal microbial transmission[J]. Chinese Journal of Reproduction and Contraception, 2017, 37(9):773-778(in Chinese)
Jiménez E, Marín M L, Martín R, et al. Is meconium from healthy newborns actually sterile?[J]. Research in Microbiology, 2008, 159(3):187-193 Aagaard K, Ma J, Antony K M, et al. The placenta harbors a unique microbiome[J]. Science Translational Medicine, 2014, 6(237):237ra65 Gosalbes M J, Vallès Y, Jiménez-Hernández N, et al. High frequencies of antibiotic resistance genes in infants' meconium and early fecal samples[J]. Journal of Developmental Origins of Health and Disease, 2015, 7(1):35-44 关怀, 齐宸, 武晓旭, 等. 胎儿肠道菌群定植的研究进展[J]. 人民军医, 2019, 62(8):764-767 Kelsall B. Recent progress in understanding the phenotype and function of intestinal dendritic cells and macrophages[J]. Mucosal Immunology, 2008, 1(6):460-469 Pärnänen K, Karkman A, Hultman J, et al. Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements[J]. Nature Communications, 2018, 9(1):3891 Dominguez-Bello M G, Costello E K, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns[J]. Proceedings of the National Academy of Sciences, 2010, 107(26):11971-11975 Martín R, Langa S, Reviriego C, et al. Human milk is a source of lactic acid bacteria for the infant gut[J]. The Journal of Pediatrics, 2003, 143(6):754-758 Rizzo L, Manaia C, Merlin C, et al. Urban wastewater treatment plants as hotspots for antibiotic resistant bacteria and genes spread into the environment:A review[J]. Science of the Total Environment, 2013, 447:345-360 Karkman A, Pärnänen K, Larsson D G J. Fecal pollution can explain antibiotic resistance gene abundances in anthropogenically impacted environments[J]. Nature Communications, 2019, 10(1):80 马筱玲, 鲁怀伟, 张艳. 认识细菌的天然耐药和获得性耐药[J]. 中华检验医学杂志, 2012, 35(8):762-763 Cox G, Wright G D. Intrinsic antibiotic resistance:Mechanisms, origins, challenges and solutions[J]. International Journal of Medical Microbiology, 2013, 303(6-7):287-292 Dodd M C. Potential impacts of disinfection processes on elimination and deactivation of antibiotic resistance genes during water and wastewater treatment[J]. Journal of Environmental Monitoring, 2012, 14(7):1754-1771 Nordgård L, Brusetti L, Raddadi N, et al. An investigation of horizontal transfer of feed introduced DNA to the aerobic microbiota of the gastrointestinal tract of rats[J]. BMC Research Notes, 2012, 5(1):170 Stinear T P, Olden D C, Johnson P D R, et al. Enterococcal van B resistance locus in anaerobic bacteria in human faeces[J]. The Lancet, 2001, 357(9259):855-856 Graham M, Ballard S A, Grabsch E A, et al. High rates of fecal carriage of nonenterococcal van B in both children and adults[J]. Antimicrobial Agents and Chemotherapy, 2008, 52(3):1195-1197 Waters J L, Salyers A A. Regulation of CTnDOT conjugative transfer is a complex and highly coordinated series of events[J]. mBio, 2013, 4(6):e00569-13 Manrique P, Dills M, Young J M. The human gut phage community and its implications for health and disease[J]. Viruses, 2017, 9(6):141 Quirós P, Colomer-Lluch M, Martínez-Castillo A, et al. Antibiotic resistance genes in the bacteriophage DNA fraction of human fecal samples[J]. Antimicrobial Agents and Chemotherapy, 2014, 58(1):606-609 Modi S R, Lee H H, Spina C S, et al. Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome[J]. Nature, 2013, 499(7457):219-222 D'costa V M, King C E, Kalan L, et al. Antibiotic resistance is ancient[J]. Nature, 2011, 477(7365):457-461 Bhullar K, Waglechner N, Pawlowski A, et al. Antibiotic resistance is prevalent in an isolated cave microbiome[J]. PLoS One, 2012, 7(4):e34953 Santiago-Rodriguez T M, Fornaciari G, Luciani S, et al. Gut microbiome of an 11th century A.D. pre-Columbian Andean mummy[J]. PLoS One, 2015, 10(9):e0138135 Miteva V I, Sheridan P P, Brenchley J E. Phylogenetic and physiological diversity of microorganisms isolated from a deep Greenland glacier ice core[J]. Applied and Environmental Microbiology, 2004, 70(1):202-213 Davies J, Davies D. Origins and evolution of antibiotic resistance[J]. Microbiology and Molecular Biology Reviews, 2010, 74(3):417-433 Zhang G, Leclercq S O, Tian J, et al. A new subclass of intrinsic aminoglycoside nucleotidyltransferases, ANT(3'')-Ⅱ, is horizontally transferred among Acinetobacter spp. by homologous recombination[J]. PLoS Genetics, 2017, 13(2):e1006602 Datta N P, Kontomichalou. Penicillinase synthesis controlled by infectious R factors in Enterobacteriaceae[J]. Nature, 1965, 208:239-241 厉文辉, 史亚利, 高立红, 等. 加速溶剂萃取-高效液相色谱-串联质谱法同时检测鱼肉中喹诺酮、磺胺与大环内酯类抗生素[J]. 分析测试学报, 2010, 29(10):987-992 Li W H, Shi Y L, Gao L H, et al. Simultaneous determination of quinolones, sulfonamides and macrolides in fish samples using accelerated solvent extraction followed by high performance liquid chromatography-electrospray ionization tandem mass spectrometry[J]. Journal of Instrumental Analysis, 2010, 29(10):987-992(in Chinese)
Bush K. Alarming β-lactamase-mediated resistance in multidrug-resistant Enterobacteriaceae[J]. Current Opinion in Microbiology, 2010, 13(5):558-564 Bradford P A. Extended-spectrum β-lactamases in the 21st Century:Characterization, epidemiology, and detection of this important resistance threat[J]. Clinical Microbiology Reviews, 2001, 14(4):933-951 Bronzwaer S L A M, Cars O, Buchholz U, et al. The relationship between antimicrobial use and antimicrobial resistance in Europe[J]. Emerging Infectious Diseases, 2002, 8(3):278-282 Tadesse D A, Zhao S, Tong E, et al. Antimicrobial drug resistance in Escherichia coli from humans and food animals, United States, 1950-2002[J]. Emerging Infectious Diseases, 2012, 18(5):741-749 Kahn L H. Perspective:The one-health way[J]. Nature, 2017, 543(7647):S47 李鹏媛, 原丽红, 陆家海. 应对新发传染病, One Health策略势在必行[J]. 传染病信息, 2018, 31(1):11-14 , 54 Li P Y, Yuan L H, Lu J H. Imperative One Health strategy for the emerging infectious diseases[J]. Infectious Disease Information, 2018, 31(1):11-14, 54(in Chinese)
刘羽. 国家自然科学基金环境地球科学学科布局优化战略研究[J]. 科学通报, 2020, doi:10.1360/TB-2020 -0424 Liu Y. Research on the strategy of optimizing the discipline layout of environmental geosciences under the National Natural Science Foundation of China[J]. Chinese Science Bulletin, 2020, doi:10.1360/TB-2020-0424(in Chinese)
-
点击查看大图
计量
- 文章访问数: 5206
- HTML全文浏览数: 5206
- PDF下载数: 171
- 施引文献: 0
下载:
