广州市熟肉制品微生物污染状况及其耐药性传播研究
|
摘要
食源性病原菌感染引起的各种疾病是食品安全的主要问题之一，大量研究表明，在食用动物中使用抗生素导致耐药菌株出现，动物感染的耐药细菌可以通过直接接触、食物链和环境污染将其耐药性及其耐药基因传播给人类，这已构成了一个巨大并不断扩大的世界性公共卫生问题
随着人们生活节奏加快，熟肉制品因其味道佳、食用方便成为广大群众餐桌上不可缺少的佳肴。但由于熟肉制品从制作到食用，存在着流通环节多、存放时间长等特点，且由于其营养丰富更成为细菌生长的天然培养基，极易造成微生物污染，从而造成食源性疾病的发生。
因此，本论文针对广州市部分超市及农贸市场熟食柜台的熟肉制品，采用简单随机取样的方法，选用兽药和临床中使用较早、使用量较大的四环素、红霉素和磺胺甲基异恶唑三种抗生素，研究其微生物及耐药微生物污染状况及可移动耐药基因元件介导的食源性致病菌播散耐药性的分子机制。本研究按月份从超市及自由市场取得46份即食熟肉样本，研究表明：自由市场所出售的熟肉制品受微生物的污染程度(104CFU g-1)大于超市所售熟肉制品的微生物污染程度(103CFU g-1)，但是从抗生素耐药角度比较，来自自由市场的熟肉制品微生物耐药率（1.2%）却要小于超市中熟肉制品微生物的耐药率（5.3%）。通过PCR方法及生化鉴定方法，共发现即食熟肉制品中携带四环素，红霉素及磺胺甲基异恶唑抗生素耐药基因的菌株34株；从抗性菌落分布情况来看，污染的耐药葡萄球菌数量多达10株，作为常见的环境条件致病菌，这一结果属于正常范围；其次李斯特菌为8株，值得警示的是其中4株为单核细胞增生李斯特菌，单增李斯特菌在即食熟肉制品中被检测到说明食品微生物安全存在较大问题；肠杆菌作为评价食品卫生质量的重要指标之一，本次实验中捡出7株耐药肠杆菌，列第三位；奇异变形杆菌作为近年来受重视的一种条件致病，在此次实验中检出到4株携带耐药基因，排在第四位。通过脉冲场凝胶电泳技术对熟肉制品检出的典型微生物进行指纹图谱和溯源分析，发现耐药基因分布与地域有较大的关系。针对发现携带耐药基因的微生物，通过southern杂交、结合转移(Conjugation)、等实验手段计算出熟肉制品检出耐药菌之间耐药基因的接合转移效率为3.1×10~(-9)，这一数据低于美国此前相关的报道。同时研究表明1株单核细胞增生李斯特菌携带的四环素耐药基因tet(M)位于具有水平传播耐药基因能力的接合型转座子Tn916上，这种转座子介导的四环耐药机制加速了耐药基因在菌株间的广泛散播，由可播，由可移动基因元件介导的耐药性能够在各种食源性致病菌中传递，这无疑会给食品安全带来危害，临床治疗带来困难。
本研究为食源性疾病的快速反应、预警和控制食源性致病菌引起的食品安全问题提供基础数据和科学技术依据。
Resistant pathogens to various antibiotics are emerging rapidly. Surfacing of theseresistant pathogens, untreatable by antibiotics, constitutes a real threat to public health inmajority studies. A Cooked meat product is ready-to-eat (RTE) food which usually exposed tothe air directly and set a long shelf-life by manufacturers, and taking account of itsparticularly suitable nutrient structure for microbial growth it is inevitable that such food iseasily contaminated by microorganisms in course of processing, transporting and selling.More importantly, it presents an immediate risk to public health because these products aregenerally consumed directly without the secondary processing. However data on theprevalence of resistance bacteria from cooked meat samples are unfortunately sparse in Chinaas the result of focusing on the several common pathogens previously and are urgently neededfor scientific assessment of the potential health impact to human.
The purpose of this study was to evaluate the prevalence of resistance commensalmicrobes and resistance genes among46retail cooked meat products (including12chicken，11duck,12pork and11gut) obtained from six separate supermarkets and two free marketsin Guangzhou. Bacteria resistance to sulfamethoxazole-trimethoprim (Sul/Tmp), tetracycline(Tet) and erythromycin (Em), the three antibiotics widely used in clinical and animal therapywere investigated. The SulR, EmRTetRisolates was observed most frequently among ducksamples, followed by chicken and pork. On the whole the number of SulRmicrobes wasgreater than that of ErmRand TetRbacteria in all the food samples. The presence of102–104CFUg-1of ART bacteria per gram of foods in many samples. The tetM, tetS, tetL,ermB and sulII were found to be the predominant genes in the isolates respectively. Isolateswere identified at the genus level. The result displayed that Staphylococcus, Enterobacter,and Listeria were more prevalent among the resistance isolates. In conclusion the cookedmeat products are contaminated by bacteria acutely and the widespread distribution ofresistant strains observed may reflect the extent of use of antibiotics in specific food animalproduction environments. Given the importance of Resistant pathogens in mediating theresistance gene dissemination, with the method of southern plotting and Conjugation, furtherinvestigations are required to identify these strains carrying resistance genes to species andanalyze whether the genes might be horizontally transferred to other species. The rate ofConjugation was3.1×10-9which was lower than previous study in US. This study has shownthat Listeria monocytogenes carrying the tetracycline resistance gene tetM located on the horizontal transmission of resistance gene of the mating type transposon Tn916. This will nodoubt give a food safety hazards, clinical treatment difficult.
The aim of this study was to evaluate the prevalence of resistance resistance genesamong cooked meat products early warning and control food borne pathogens cause foodsafety problems to provide the basic data and scientific and technical basis.
随着人们生活节奏加快，熟肉制品因其味道佳、食用方便成为广大群众餐桌上不可缺少的佳肴。但由于熟肉制品从制作到食用，存在着流通环节多、存放时间长等特点，且由于其营养丰富更成为细菌生长的天然培养基，极易造成微生物污染，从而造成食源性疾病的发生。
因此，本论文针对广州市部分超市及农贸市场熟食柜台的熟肉制品，采用简单随机取样的方法，选用兽药和临床中使用较早、使用量较大的四环素、红霉素和磺胺甲基异恶唑三种抗生素，研究其微生物及耐药微生物污染状况及可移动耐药基因元件介导的食源性致病菌播散耐药性的分子机制。本研究按月份从超市及自由市场取得46份即食熟肉样本，研究表明：自由市场所出售的熟肉制品受微生物的污染程度(104CFU g-1)大于超市所售熟肉制品的微生物污染程度(103CFU g-1)，但是从抗生素耐药角度比较，来自自由市场的熟肉制品微生物耐药率（1.2%）却要小于超市中熟肉制品微生物的耐药率（5.3%）。通过PCR方法及生化鉴定方法，共发现即食熟肉制品中携带四环素，红霉素及磺胺甲基异恶唑抗生素耐药基因的菌株34株；从抗性菌落分布情况来看，污染的耐药葡萄球菌数量多达10株，作为常见的环境条件致病菌，这一结果属于正常范围；其次李斯特菌为8株，值得警示的是其中4株为单核细胞增生李斯特菌，单增李斯特菌在即食熟肉制品中被检测到说明食品微生物安全存在较大问题；肠杆菌作为评价食品卫生质量的重要指标之一，本次实验中捡出7株耐药肠杆菌，列第三位；奇异变形杆菌作为近年来受重视的一种条件致病，在此次实验中检出到4株携带耐药基因，排在第四位。通过脉冲场凝胶电泳技术对熟肉制品检出的典型微生物进行指纹图谱和溯源分析，发现耐药基因分布与地域有较大的关系。针对发现携带耐药基因的微生物，通过southern杂交、结合转移(Conjugation)、等实验手段计算出熟肉制品检出耐药菌之间耐药基因的接合转移效率为3.1×10~(-9)，这一数据低于美国此前相关的报道。同时研究表明1株单核细胞增生李斯特菌携带的四环素耐药基因tet(M)位于具有水平传播耐药基因能力的接合型转座子Tn916上，这种转座子介导的四环耐药机制加速了耐药基因在菌株间的广泛散播，由可播，由可移动基因元件介导的耐药性能够在各种食源性致病菌中传递，这无疑会给食品安全带来危害，临床治疗带来困难。
本研究为食源性疾病的快速反应、预警和控制食源性致病菌引起的食品安全问题提供基础数据和科学技术依据。
Resistant pathogens to various antibiotics are emerging rapidly. Surfacing of theseresistant pathogens, untreatable by antibiotics, constitutes a real threat to public health inmajority studies. A Cooked meat product is ready-to-eat (RTE) food which usually exposed tothe air directly and set a long shelf-life by manufacturers, and taking account of itsparticularly suitable nutrient structure for microbial growth it is inevitable that such food iseasily contaminated by microorganisms in course of processing, transporting and selling.More importantly, it presents an immediate risk to public health because these products aregenerally consumed directly without the secondary processing. However data on theprevalence of resistance bacteria from cooked meat samples are unfortunately sparse in Chinaas the result of focusing on the several common pathogens previously and are urgently neededfor scientific assessment of the potential health impact to human.
The purpose of this study was to evaluate the prevalence of resistance commensalmicrobes and resistance genes among46retail cooked meat products (including12chicken，11duck,12pork and11gut) obtained from six separate supermarkets and two free marketsin Guangzhou. Bacteria resistance to sulfamethoxazole-trimethoprim (Sul/Tmp), tetracycline(Tet) and erythromycin (Em), the three antibiotics widely used in clinical and animal therapywere investigated. The SulR, EmRTetRisolates was observed most frequently among ducksamples, followed by chicken and pork. On the whole the number of SulRmicrobes wasgreater than that of ErmRand TetRbacteria in all the food samples. The presence of102–104CFUg-1of ART bacteria per gram of foods in many samples. The tetM, tetS, tetL,ermB and sulII were found to be the predominant genes in the isolates respectively. Isolateswere identified at the genus level. The result displayed that Staphylococcus, Enterobacter,and Listeria were more prevalent among the resistance isolates. In conclusion the cookedmeat products are contaminated by bacteria acutely and the widespread distribution ofresistant strains observed may reflect the extent of use of antibiotics in specific food animalproduction environments. Given the importance of Resistant pathogens in mediating theresistance gene dissemination, with the method of southern plotting and Conjugation, furtherinvestigations are required to identify these strains carrying resistance genes to species andanalyze whether the genes might be horizontally transferred to other species. The rate ofConjugation was3.1×10-9which was lower than previous study in US. This study has shownthat Listeria monocytogenes carrying the tetracycline resistance gene tetM located on the horizontal transmission of resistance gene of the mating type transposon Tn916. This will nodoubt give a food safety hazards, clinical treatment difficult.
The aim of this study was to evaluate the prevalence of resistance resistance genesamong cooked meat products early warning and control food borne pathogens cause foodsafety problems to provide the basic data and scientific and technical basis.
引文
[1] Pan.Z. Changes in antimicrobial resistance among Salmonella enterica subspeciesenterica serovar Pullorum isolates in China from1962to2007. Veterinarymicrobiology,2009.136(3-4): p.387-392.
[2] Kohler R., Krause G., Beutin L., et al. Shedding of food-borne pathogens andmicrobiological carcass contamination in rabbits at slaughter. Veterinary microbiology.2008,132(1-2):149-157.
[3] Yang B., Qu D., Zhang X., et al. Prevalence and characterization of Salmonellaserovars in retail meats of marketplace in Shaanxi, China. International journal of foodmicrobiology.2010,141(1):63-72.
[4]刘秀梅.我国食品卫生微生物学30年来的热点研究及主要进展.中国食品卫生杂志.2009,21(004):289-295.
[5]王茂起，冉陆，王竹天，等.2001年中国食源性致病菌及其耐药性主动监测研究.卫生研究.2004,33(1):49-54.
[6]张亚兰，冉陆，李迎惠，等.2003—2004年中国食品中单核细胞增生李斯特菌耐药监测.中国食品卫生杂志.2006,18(5):398-400.
[7]杨洋，付萍，郭云昌，等.2005年中国食源性单核细胞增生李斯特菌耐药性趋势分析.卫生研究.2008,37(2):183-186.
[8]刘秀梅，程苏云，陈艳，等.2003年中国部分沿海地区零售海产品中副溶血性弧菌污染状况的主动监测.中国食品卫生杂志.2005,17(2):97-99.
[9] Marshall B.M., Ochieng D.J., Levy S.B. Commensals: underappreciated reservoir ofantibiotic resistance. Microbe.2009,4:231-238.
[10]金少鸿，马越.国内细菌耐药性监测研究的回顾与展望.中国抗生素杂志.2005,30(5):257-259.
[11] Kova evi J., Mesak L.R., Allen K.J. Occurrence and Characterization of Listeriaspp.in Ready-to-Eat Retail Foods from Vancouver, British Columbia. Food Microbiology.2012.
[12] White D.G., Zhao S., Sudler R., et al. The isolation of antibiotic-resistant Salmonellafrom retail ground meats. New England Journal of Medicine.2001,345(16):1147-1154.
[13] Chen S., Zhao S., White D.G., et al. Characterization of multiple-antimicrobial-resistantSalmonella serovars isolated from retail meats. Applied and environmentalmicrobiology.2004,70(1):1-7.
[14] Bielaszewska M., Mellmann A., Zhang W., et al. Characterisation of the Escherichiacoli strQain associated with an outbreak of haemolytic uraemic syndrome in Germany,2011: a microbiological study. The Lancet infectious diseases.2011.
[15] Rohde H., Qin J., Cui Y., et al. Open-source genomic analysis of shiga-toxin–producingE. coli O104: H4. New England Journal of Medicine.2011.
[16]赵悦，付萍，裴晓燕，等.中国食源性单核细胞增生李斯特菌耐药特征分析.中国食品卫生杂志.2012,1.
[17] Uyttendaele M., Busschaert P., Valero A., et al. Prevalence and challenge tests ofListeria monocytogenesin Belgian produced and retailed mayonnaise-based deli-salads,cooked meat products and smoked fish between2005and2007. International journal offood microbiology.2009,133(1):94-104.
[18]葛明，江晓，包亚慧.速冻米面制品中食源性致病菌污染调查.江苏卫生保健:学术版.2010,12(001):12-13.
[19] Bundrant B.N., Hutchins T., Bakker H.C., et al. Listeriosis outbreak in dairy cattlecaused by an unusual Listeria monocytogenes serotype4b strain. Journal of VeterinaryDiagnostic Investigation.2011,23(1):155-158.
[20] Bohaychuk V M, Gensler G E, King R K, et al. Occurrence of pathogens in raw andready-to-eat meat and poultry products collected from the retail marketplace inEdmonton, Alberta, Canada. Journal of Food Protection174.2006,69(9):2176-2182.
[21] Chasseignaux E., Gérault P., Toquin M.T., et al. Ecology of Listeria monocytogenes inthe environment of raw poultry meat and raw pork meat processing plants. FEMSmicrobiology letters.2002,210(2):271-275.
[22] Charpentier E., Courvalin P. Antibiotic Resistance in Listeriaspp. Antimicrobial agentsand chemotherapy.1999,43(9):2103-2108.
[23] S rum H., L'Abée-Lund T.M. Antibiotic resistance in food-related bacteria—a result ofinterfering with the global web of bacterial genetics. International journal of foodmicrobiology.2002,78(1):43-56.
[24] Clark C.G., Farber J., Pagotto F., et al. Surveillance for Listeria monocytogenes andlisteriosis,1995–2004. Epidemiology and infection.2010,138(04):559-572.
[25] Kümmerer K. Resistance in the environment. Journal of Antimicrobial Chemotherapy.2004,54(2):311-320.
[26] Cruchaga S., Echeita A., Aladue a A., et al. Antimicrobial resistance in salmonellaefrom humans, food and animals in Spain in1998. Journal of AntimicrobialChemotherapy.2001,47(3):315-321.
[27] Wells S.J., Fedorka-Cray P.J, Dargatz D.A., et al. Fecal shedding of Salmonella spp.by dairy cows on farm and at cull cow markets. Journal of Food Protection®.2001,64(1):3-11.
[28] Cogan T.A. Campylobacter jejuni is associated with, but not sufficient to causevibrionic hepatitis in chickens. Veterinary Microbiology.2010.
[29] H nel I., Borrmann E., Müller J., et al. Genomic and phenotypic changes ofCampylobacter jejuni strains after passage of the chicken gut. Veterinarymicrobiology.2009,136(1-2):121-129.
[30] Han K., Jang S.S., Choo E., et al. Prevalence, genetic diversity, and antibioticresistance patterns of Campylobacter jejuni from retail raw chickens inKorea. International journal of food microbiology.2007,114(1):50-59.
[31]毕水莲，李琳，唐书泽，等.变形杆菌属食物中毒的特点与防控措施.现代食品科技.2009(006):690-695.
[32] Kwon N.H., Park K.T., Jung W.K., et al. Characteristics of methicillin resistantStaphylococcus aureus isolated from chicken meat and hospitalized dogs in Koreaand their epidemiological relatedness. Veterinary microbiology.2006,117(2):304-312.
[33] Velusamy V., Arshak K., Korostynska O., et al. An overview of foodborne pathogendetection: In the perspective of biosensors. Biotechnology advances.2010,28(2):232-254.
[34] O'Brien T.F. Emergence, spread, and environmental effect of antimicrobial resistance:how use of an antimicrobial anywhere can increase resistance to any antimicrobialanywhere else. Clinical Infectious Diseases.2002,34(Supplement3): S78-S84.
[35] Khachatourians G.G. Agricultural use of antibiotics and the evolution and transfer ofantibiotic-resistant bacteria. Canadian Medical Association Journal.1998,159(9):1129-1136.
[36] Mellon M., Benbrook C., Benbrook K.L. Hogging it. Estimates of AntimicrobialAbuse in Livestock (Cambridge, MA: Union of Concerned Scientists).2001.
[37] Hendrickson H., Slechta E.S., Bergthorsson U., et al. Amplification–mutagenesis:Evidence that “directed” adaptive mutation and general hypermutability result fromgrowth with a selected gene amplification. Proceedings of the National Academy ofSciences.2002,99(4):2164.
[38] Howden B.P., Ward P.B., Charles P.G.P., et al. Treatment outcomes for seriousinfections caused by methicillin-resistant Staphylococcus aureus with reducedvancomycin susceptibility. Clinical infectious diseases.2004,38(4):521-528.
[39] Szapiel S.V., Elson N.A., Fulmer J.D., et al. Bleomycin-induced interstitialpulmonary disease in the nude, athymic mouse. The American review of respiratorydisease.1979,120(4):893.
[40] Corkill J.E., Anson J.J., Hart C.A. High prevalence of the plasmid-mediatedquinolone resistance determinant qnrA in multidrug-resistant Enterobacteriaceaefrom blood cultures in Liverpool, UK. Journal of Antimicrobial Chemotherapy.2005,56(6):1115-1117.
[41]张心如，罗宜熟，杜干英，等.动物源性耐药菌与人类安全.兽药与饲料添加剂.2004,9(003):3-6.
[42]廖龙标.水环境生物污染的分子生物学检测及其修复的初步研究[D].中国科学院研究生院(广州地球化学研究所),2006.
[43] Depardieu F., Podglajen I., Leclercq R., et al. Modes and modulations of antibioticresistance gene expression. Clinical microbiology reviews.2007,20(1):79-114.
[44] Aase B., Sundheim G., Langsrud S., et al. Occurrence of and a possible mechanismfor resistance to a quaternary ammonium compound in Listeriamonocytogenes. International journal of food microbiology.2000,62(1):57-63.
[45] Mah T.F.C., O'Toole G.A. Mechanisms of biofilm resistance to antimicrobial agents.Trends in microbiology.2001,9(1):34-39.
[46] Whitchurch C.B., Tolker-Nielsen T., Ragas P.C., et al. Extracellular DNA requiredfor bacterial biofilm formation. Science.2002,295(5559):1487.
[47] Heffron F., Mccarthy B.J., Ohtsubo H., et al. DNA sequence analysis of thetransposon Tn3: three genes and three sites involved in transposition of Tn3. Cell.1979,18(4):1153.
[48] Hall R.M., Collis C.M. Mobile gene cassettes and integrons: capture and spread ofgenes by site‐specific recombination. Molecular microbiology.1995,15(4):593-600.
[49] Hall R.M., Collis C.M., Kim M. J., et al. Mobile gene cassettes and integrons inevolution. Annals of the New York Academy of Sciences.1999,870(1):68-80.
[50] Hall R.M., Stokes H.W. Integrons or super integrons? Microbiology.2004,150(1):3-4.
[51] Hall R.M., Brookes D.E., Stokes H.W. Site‐specific insertion of genes intointegrons: role of the59‐base element and determination of the recombination cross‐over point. Molecular microbiology.1991,5(8):1941-1959.
[52] Collis C.M., Kim M.J., Partridge S.R., et al. Characterization of the class3integronand the site-specific recombination system it determines. Journal of bacteriology.2002,184(11):3017-3026.
[53] Correia M., Boavida F., Grosso F., et al. Molecular characterization of a new class3integron in Klebsiella pneumoniae. Antimicrobial agents and chemotherapy.2003,47(9):2838-2843.
[54] Léon G., Roy P.H. Excision and integration of cassettes by an integron integrase ofNitrosomonas europaea. Journal of bacteriology.2003,185(6):2036-2041.
[55] Gravel A., Messier N., Roy P.H. Point mutations in the integron integrase IntI1thataffect recombination and/or substrate recognition. Journal of bacteriology.1998,180(20):5437-5442.
[56]张翊，裴德宁. RNA干扰研究进展.中国肿瘤生物治疗杂志.2003,10(1):68-70.
[57] Ni J., Clark K.J., Fahrenkrug S.C., et al. Transposon tools hopping in vertebrates.Briefings in functional genomics&proteomics.2008,7(6):444-453.
[58] Ivics Z., Kaufman C.D., Zayed H., et al. The Sleeping Beauty transposable element:evolution, regulation and genetic applications. Current Issues in Molecular Biology.2004,6:43-56.
[59] Meng H., Zhang Z., Chen M., et al. Characterization and horizontal transfer of class1integrons in Salmonella strains isolated from food products of animal origin.International Journal of Food Microbiology.2011.
[60]顾宝柯，许学斌，金汇明，等.上海地区家畜,家禽及肉制品大肠杆菌O157: H7监测.疾病监测.2003,18(1):5-7.
[61] Robredo B., Singh K.V., Baquero F., et al. Vancomycin-resistant enterococci isolatedfrom animals and food. International journal of food microbiology.2000,54(3):197-204.
[62] Pezzotti G., Serafin A., Luzzi I., et al. Occurrence and resistance to antibiotics ofCampylobacter jejuni andCampylobacter coli in animals and meat in northeasternItaly. International journal of food microbiology.2003,82(3):281-287.
[63] Mead P.S., Slutsker L., Dietz V., et al. Food-related illness and death in the UnitedStates. Emerging infectious diseases.1999,5(5):607.
[64] Salyers A.A., Gupta A., Wang Y. Human intestinal bacteria as reservoirs forantibiotic resistance genes. Trends in microbiology.2004,12(9):412-416.
[65] Macdonald J.M., Ollinger M.E., Nelson K.E., et al. Structural change in meatindustries: implications for food safety regulation. American journal of agriculturaleconomics.1996,78(3):780-785.
[66] S rensen T.L., Blom M., Monnet D.L., et al. Transient intestinal carriage afteringestion of antibiotic-resistant Enterococcus faecium from chicken and pork. NewEngland Journal of Medicine.2001,345(16):1161-1166.
[67] Shoemaker N.B., Vlamakis H., Hayes K., et al. Evidence for Extensive ResistanceGene Transfer amongBacteroides spp. and among Bacteroides and Other Genera inthe Human Colon. Applied and Environmental Microbiology.2001,67(2):561-568.
[68] Aarestrup F.M., Seyfarth A.M., Emborg H.D., et al. Effect of abolishment of the useof antimicrobial agents for growth promotion on occurrence of antimicrobialresistance in fecal enterococci from food animals in Denmark. Antimicrobial Agentsand chemotherapy.2001,45(7):2054-2059.
[69]马永生，徐永平，金礼吉，等.饲用抗生素细菌耐药性的研究进展.中国饲料.2005(12):5-7.
[70]魏荣，王志亮.细菌耐药性基因与食品卫生安全.中国动物保健.2003(011):17-18.
[71] Blake D.P., Humphry R.W., Scott K.P., et al. Influence of tetracycline exposure ontetracycline resistance and the carriage of tetracycline resistance genes withincommensal Escherichia coli populations. Journal of applied microbiology.2003,94(6):1087-1097.
[72] Roberts M.C. Update on acquired tetracycline resistance genes. FEMS microbiologyletters.2005,245(2):195-203.
[73] Connell S.R., Trieber C.A., Dinos G.P., et al. Mechanism of Tet (O)-mediatedtetracycline resistance. The EMBO journal.2003,22(4):945-953.
[74] Recchia G.D., Hall R.M. Gene cassettes: a new class of mobile element.Microbiology.1995,141(12):3015-3027.
[75] Huovinen P., Sundstr m L., Swedberg G., et al. Trimethoprim and sulfonamideresistance. Antimicrobial agents and chemotherapy.1995,39(2):279.
[76] Sk ld O. Resistance to trimethoprim and sulfonamides. Veterinary research.2001,32(3-4):261-273.
[77] Trine M.L., S rum H. Functional Tn5393-like transposon in the R plasmid pRAS2from the fish pathogen Aeromonas salmonicida subspecies salmonicida isolated inNorway. Applied and environmental microbiology.2000,66(12):5533-5535.
[78] Yazdankhah S.P., S rum H., Oppegaard H. Comparison of genes involved inpenicillin resistance in staphylococci of bovine origin. Microbial Drug Resistance.2000,6(1):29-36.
[1] Falsafi T., Mobasheri F., Nariman F., et al. Susceptibilities to different antibiotics ofHelicobacter pylori strains isolated from patients at the pediatric medical center ofTehran, Iran[J]. Journal of clinical microbiology.2004,42(1):387-389.
[2] Chopra I., Roberts M. Tetracycline antibiotics: mode of action, applications, molecularbiology, and epidemiology of bacterial resistance[J]. Microbiology and MolecularBiology Reviews.2001,65(2):232-260.
[3]代敏，王雄清，殷桂兰.四环素耐药基因的生化和遗传机制研究进展[J].绵阳师范学院学报.2006,25(5):72-78.
[4] Mcnicholas P., Mcglynn M., Guay G.G., et al. Genetic analysis suggests functionalinteractions between the N-and C-terminal domains of the TetA (C) efflux pumpencoded by pBR322.[J]. Journal of bacteriology.1995,177(18):5355-5357.
[5] Iwaki S., Tamura N., Kimura-Someya T., et al. Cysteine-scanning mutagenesis oftransmembrane segments4and5of the Tn10-encoded metal-tetracycline/H+antiporterreveals a permeability barrier in the middle of a transmembrane water-filled channel[J].Journal of Biological Chemistry.2000,275(30):22704-22712.
[6] Someya Y., Kimura-Someya T., Yamaguchi A. Role of the Charge Interaction betweenArg70and Asp120in the Tn10-encoded Metal-Tetracycline/H+Antiporter ofEscherichia coli[J]. Journal of Biological Chemistry.2000,275(1):210-214.
[7] Doran J.L., Pang Y., Mdluli K.E., et al. Mycobacterium tuberculosis efpA encodes anefflux protein of the QacA transporter family.[J]. Clinical and diagnostic laboratoryimmunology.1997,4(1):23-32.
[8] Burdett V. Tet (M)-promoted release of tetracycline from ribosomes is GTPdependent.[J]. Journal of bacteriology.1996,178(11):3246-3251.
[9] Roberts M.C. Update on acquired tetracycline resistance genes[J]. FEMS microbiologyletters.2005,245(2):195-203.
[10] Luo H., Yousef A.E., Wang H.H. A real‐time polymerase chain reaction‐basedmethod for rapid and specific detection of spoilage Alicyclobacillus spp. in applejuice[J]. Letters in applied microbiology.2004,39(4):376-382.
[11] Wang H.H., Manuzon M., Lehman M., et al. Food commensal microbes as a potentiallyimportant avenue in transmitting antibiotic resistance genes[J]. FEMS microbiologyletters.2006,254(2):226-231.
[12]邵美丽，刘思国，尹录.单增李斯特菌四环素耐药基因tetM膜接合转移的研究[J].中国兽医科学.2010,40(006):589-592.
[13] Ethelberg S., Lisby M., Torpdahl M., et al. Prolonged restaurant‐associated outbreakof multidrug‐resistant Salmonella Typhimurium among patients from severalEuropean countries[J]. Clinical microbiology and infection.2004,10(10):904-910.
[14] Pesavento G., Ducci B., Nieri D., et al. Prevalence and antibiotic susceptibility ofListeria spp. isolated from raw meat and retail foods[J]. Food Control.2010,21(5):708-713.
[15] Yücel N., Citak S., nder M. Prevalence and antibiotic resistance of Listeria species inmeat products in Ankara, Turkey[J]. Food microbiology.2005,22(2-3):241-245.
[16] Ejim L., Farha M.A., Falconer S.B., et al. Combinations of antibiotics and nonantibioticdrugs enhance antimicrobial efficacy[J]. Nature Chemical Biology.2011,7(6):348-350.
[17] Haryani Y., Noorzaleha A.S., Fatimah A.B., et al. Incidence of Klebsiella pneumonia instreet foods sold in Malaysia and their characterization by antibiotic resistance, plasmidprofiling, and RAPD–PCR analysis[J]. Food control.2007,18(7):847-853.
[1]王丽平,陆承平,动物源性链球菌红霉素耐药基因的分布.畜牧兽医学报,2005.36(9):第977-980页.
[2]糜祖煌,黄支密,秦玲,常见球菌红霉素耐药基因研究.世界感染雜誌,2006.6(6):第517-519页.
[3]张部昌,赵志虎,马清钧,红霉素基因工程研究进展.中国生物工程杂志,2002.22(3):第40-44页.
[4] Holzbaur I.E., Ranganathan A., Thomas I.P., et al. Molecular basis of Celmer's rules:role of the ketosynthase domain in epimerisation and demonstration that ketoreductasedomains can have altered product specificity with unnatural substrates[J]. Chemistry&biology.2001,8(4):329-340.
[5] Sutcliffe J., Grebe T., Tait-Kamradt A., et al. Detection of erythromycin-resistantdeterminants by PCR.[J]. Antimicrobial Agents and Chemotherapy.1996,40(11):2562-2566.
[6] Pechère J.C. Macrolide resistance mechanisms in Gram-positive cocci[J]. Internationaljournal of antimicrobial agents.2001,18:25-28.
[7] Tait-Kamradt A., Davies T., Appelbaum P.C., et al. Two New Mechanisms ofMacrolide Resistance in Clinical Strains ofStreptococcus pneumoniae from EasternEurope and North America[J]. Antimicrobial agents and chemotherapy.2000,44(12):3395-3401.
[8] Bingen E., Leclercq R., Fitoussi F., et al. Emergence of group A streptococcus strainswith different mechanisms of macrolide resistance[J]. Antimicrobial agents andchemotherapy.2002,46(5):1199-1203.
[9] Wang H.H., Manuzon M, Lehman M, et al. Food commensal microbes as a potentiallyimportant avenue in transmitting antibiotic resistance genes[J]. FEMS microbiologyletters.2006,254(2):226-231.
[10] Eady E.A., Ross J.I., Tipper J.L., et al. Distribution of genes encoding erythromycinribosomal methylases and an erythromycin efflux pump in epidemiologically distinctgroups of staphylococci[J]. Journal of Antimicrobial Chemotherapy.1993,31(2):211-217.
[11] Roberts M.C., Sutcliffe.J, Courvalin P., et al. Nomenclature for macrolide andmacrolide-lincosamide-streptogramin B resistance determinants[J]. AntimicrobialAgents and Chemotherapy.1999,43(12):2823-2830.
[12] Poyart-Salmeron C., Carlier C., Trieu-Cuot P., et al. Transferable plasmid-mediatedantibiotic resistance in Listeria monocytogenes[J]. The Lancet.1990,335(8703):1422-1426.
[13] Okitsu N., Kaieda S., Yano H., et al. Characterization of ermB gene transposition byTn1545and Tn917in macrolide-resistant Streptococcus pneumoniae isolates[J]. Journalof clinical microbiology.2005,43(1):168-173.
[14] White D.G., Zhao S., Simjee S., et al. Antimicrobial resistance of foodbornepathogens[J]. Microbes and infection.2002,4(4):405-412.
[1] Mckinney C.W., Loftin K.A., Meyer M.T., et al. Tet and sul antibiotic resistance genesin livestock lagoons of various operation type, configuration, and antibioticoccurrence[J]. Environmental science&technology.2010.
[2]王继东，钱小毛，郁敏.大肠埃希菌连续分离株耐药性与三类整合酶基因的研究[J].世界感染杂志.2007,6(6):520-522.
[3] Sheng W.H., Ko W.J., Wang J.T., et al. Evaluation of antiseptic-impregnated centralvenous catheters for prevention of catheter-related infection in intensive care unitpatients[J]. Diagnostic microbiology and infectious disease.2000,38(1):1-5.
[4]钱秀萍，陈代杰.细菌耐药性机制的研究与新药开发Ⅳ:兽用抗菌药物与细菌耐药性及新药研究[J].国外医药:合成药.生化药.制剂分册.2001,22(6):326-329.
[5] Yun M.K., Wu Y., Li Z., et al. Catalysis and Sulfa Drug Resistance in DihydropteroateSynthase[J]. Science.2012,335(6072):1110-1114.
[6]叶金艳，祝建军，杜玉海，等.志贺菌属对复方新诺明耐药相关基因研究[J].中华医院感染学杂志.2009(002):142-144.
[7] Chen S., Zhao S., White D.G., et al. Characterization of multiple-antimicrobial-resistantSalmonella serovars isolated from retail meats[J]. Applied and environmentalmicrobiology.2004,70(1):1-7.
[8]王继东，糜祖煌，钱小毛.套式PCR法检测肺炎克雷伯菌染色体介导β-内酰胺酶基因[J].中华医院感染学杂志.2007,17(1):8-10.
[9]张嵘，蔡加昌，胡云建，等. IMP-4型金属β内酰胺酶合并膜孔蛋白OmpK36缺失引起肺炎克雷伯菌对碳青霉烯类抗生素高水平耐药[J].中华检验医学杂志.2010,33(9):845-851.
[10]黄支密，糜家睿，盛以泉，等.携带blaKPC-2型碳青霉烯酶基因泛耐药肺炎克雷伯菌医院内感染暴发的病原学分析[J].中华流行病学杂志.2010(5):559-562.
[11]黄支密，糜祖煌，邹玉秀，等.肺炎克雷伯菌中检出16S rRNA甲基化酶基因rmtB及β内酰胺酶基因blaLAP-2[J].中华检验医学杂志.2009,31(11):1268-1269.
[12] Mermel L.A. New technologies to prevent intravascular catheter-related bloodstreaminfections.[J]. Emerging infectious diseases.2001,7(2):197.
[13] McCay P.H., Ocampo-Sosa A.A., Fleming G.T.A. Effect of subinhibitoryconcentrations of benzalkonium chloride on the competitiveness of Pseudomonasaeruginosa grown in continuous culture[J]. Microbiology.2010,156(1):30-38.
[14] Huet A.A., Raygada J.L., Mendiratta K., et al. Multidrug efflux pump overexpression inStaphylococcus aureus after single and multiple in vitro exposures to biocides anddyes[J]. Microbiology.2008,154(10):3144-3153.
[1] Dice L.R. Measures of the amount of ecologic association between species[J]. Ecology.1945,26(3):297-302.
[2] Hunter P.R, Gaston M.A. Numerical index of the discriminatory ability of typingsystems: an application of Simpson's index of diversity.[J]. Journal of clinicalmicrobiology.1988,26(11):2465-2466.
[3] Ribot E.M., Fair M.A., Gautom R., et al. Standardization of pulsed-field gelelectrophoresis protocols for the subtyping of Escherichia coli O157: H7, Salmonella,and Shigella for PulseNet[J]. Foodbourne Pathogens&Disease.2006,3(1):59-67.
[4] Andrighetto C., Zampese L., Lombardi A. RAPD‐PCR characterization of lactobacilliisolated from artisanal meat plants and traditional fermented sausages of Veneto region(Italy)[J]. Letters in Applied Microbiology.2001,33(1):26-30.
[5]刘金华，贺丹，杨艳秋，等.多位点测序分型技术在病原微生物分型鉴定中的应用[J].微生物学通报.2007,34(6):1188-1191.
[6] Tenover F.C., Arbeit R.D., Goering R.V., et al. Interpreting chromosomal DNArestriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterialstrain typing.[J]. Journal of clinical microbiology.1995,33(9):2233.
[7]付英梅，马佳毓，赵月辉.脉冲凝胶电泳技术在细菌学上的应用[J].中国卫生检验杂志.1999,9(1):72-74.
[8]姜晓冰，石磊.单核细胞增生李斯特菌脉冲场凝胶电泳分型[J].食品与机械.2009(003):84-86.
[9] WHO. Risk assessment of Listeria monocytogenes in ready-to-eat foods[J].
[10]田静，刘秀梅.熟肉制品和蔬菜沙拉中单核细胞增生李斯特菌的风险分级评估[J].中华预防医学杂志.2009,43(009):781-784.
[1] Luo, Y., Xu, L., Rysz, M., et al.2005. Occurrence and transport of tetracycline,sulfonamide, quinolone, and macrolide antibiotics in the haihe river basin, China.Environmental Science and Technology19,481-487.
[2] Crecchio C., Ruggiero P., Curci M., et al.2005. Binding of DNA from Bacillus subtilison montmorillonite-humic acids-aluminum or iron hydroxypolymers: Effects ontransformation and protection against DNase. Soil Science Society of America Journal69,834-841.
[3] Zhang X.X., Zhang T Fang HHP.2009Antibiotic resistance genes in water environment.Applied Microbiology and Biotechnology82,397-414.
[4] Rysz M., Alvarez PJJ.2004Amplification and attenuation of tetracycline resistance insoil bacteria: aquifer column experiments. Water research38,3705-3712.
[5] Srum H., Labee Lund TM.2002Antibiotic resistance in food-related bacteria--a resultof interfering with the global web of bacterial genetics. International Journal of FoodMicrobiology78,43-56.
[6] Pruden A., Pei R., Storteboom H., et al. Antibiotic Resistance Genes as EmergingContaminants: Studies in Northern Colorado. Environmental Science Technology40,7445-7450.
[7] Dantas G., Sommer M., Oluwasegun R.D., et al.2008. Bacteria subsisting on antibiotics.Science320,100-104.
[8] Marraffini, L.A., Sontheimer, E.J.2008. CRISPR interference limits horizontal genetransfer in staphylococci by targeting DNA. Science322,1843-1846.
[9] Wang H., Manuzon M., Lehman M., et al.Food commensal microbes as a potentiallyimportant avenue in transmitting antibiotic resistance genes. FEMS MicrobiologyLetters2006;254:226-231.
[10] Ahmed, A.M., Shimabukuro, H., Shimamoto, T.,2009. Isolation and molecularcharacterization of multidrug-resistant strains of Escherichia coli and Salmonella fromretail chicken meat in Japan. Journal of Food Science74, M405–M410.
[11] Chen, S., Zhao, S., White, D.G., et al.2004. Characterization ofmultiple-antimicrobial-resistant Salmonella serovars isolated from retail meats. Appliedand Environmental Microbiology70,1–7.
[12] Gebreyes, W.A., Altier, C.,2002. Molecular characterization of multidrug-resistantSalmonella enterica subsp. enterica serovar typhimurium isolates from swine. Journal ofClinical Microbiology40,2813–2822.
[13] Zhao, S., Blickenstaff, K., Glenn, A., et al.2009. Beta-lactam resistance in Salmonellaisolated from retail meats in the United States National Antimicrobial ResistanceMonitoring System (NARMS):2002–2006. Applied and Environmental Microbiology75,7624–7630.
[14] Ferguson, G.C., Heinemann, J.A., Kennedy, M.A.,2002. Gene transfer betweenSalmonella enterica serovar typhimurium inside epithelial cells. Journal of Bacteriology184,2235–2242.
[15] Wang H.H., Schaffner D.W. Antibiotic resistance: how much do we know and where togo from here? Applied and Environmental Microbiology2011;9:6511-6565.
[16] Roberts M.C, Sutcliffe J., Courvalin P., et al. Nomenclature for macrolide andmacrolide-lincosamide-streptogramin B resistance determinants[J]. AntimicrobialAgents and Chemotherapy.1999,43(12):2823-2830.
[17] Hauschild T., Lüthje P., Schwarz S. Characterization of a novel type of MLS Bresistance plasmid from Staphylococcus saprophyticus carrying a constitutivelyexpressed erm(C) gene[J]. Veterinary microbiology.2006,115(1):258-263.
[18] Chopra I., Roberts M. Tetracycline antibiotics: mode of action, applications, molecularbiology, and epidemiology of bacterial resistance[J]. Microbiology and MolecularBiology Reviews.2001,65(2):232-260.
[19] Poyart C., Quesne G., Acar P., et al. Characterization of the Tn916-like transposonTn3872in a strain of Abiotrophia defectiva (Streptococcus defectivus) causingsequential episodes of endocarditis in a child[J]. Antimicrobial agents and chemotherapy.2000,44(3):790-793.
[20] Vázquez-Boland J.A., Kuhn M., Berche P., et al. Listeria pathogenesis and molecularvirulence determinants[J]. Clinical Microbiology Reviews.2001,14(3):584-64
[2] Kohler R., Krause G., Beutin L., et al. Shedding of food-borne pathogens andmicrobiological carcass contamination in rabbits at slaughter. Veterinary microbiology.2008,132(1-2):149-157.
[3] Yang B., Qu D., Zhang X., et al. Prevalence and characterization of Salmonellaserovars in retail meats of marketplace in Shaanxi, China. International journal of foodmicrobiology.2010,141(1):63-72.
[4]刘秀梅.我国食品卫生微生物学30年来的热点研究及主要进展.中国食品卫生杂志.2009,21(004):289-295.
[5]王茂起，冉陆，王竹天，等.2001年中国食源性致病菌及其耐药性主动监测研究.卫生研究.2004,33(1):49-54.
[6]张亚兰，冉陆，李迎惠，等.2003—2004年中国食品中单核细胞增生李斯特菌耐药监测.中国食品卫生杂志.2006,18(5):398-400.
[7]杨洋，付萍，郭云昌，等.2005年中国食源性单核细胞增生李斯特菌耐药性趋势分析.卫生研究.2008,37(2):183-186.
[8]刘秀梅，程苏云，陈艳，等.2003年中国部分沿海地区零售海产品中副溶血性弧菌污染状况的主动监测.中国食品卫生杂志.2005,17(2):97-99.
[9] Marshall B.M., Ochieng D.J., Levy S.B. Commensals: underappreciated reservoir ofantibiotic resistance. Microbe.2009,4:231-238.
[10]金少鸿，马越.国内细菌耐药性监测研究的回顾与展望.中国抗生素杂志.2005,30(5):257-259.
[11] Kova evi J., Mesak L.R., Allen K.J. Occurrence and Characterization of Listeriaspp.in Ready-to-Eat Retail Foods from Vancouver, British Columbia. Food Microbiology.2012.
[12] White D.G., Zhao S., Sudler R., et al. The isolation of antibiotic-resistant Salmonellafrom retail ground meats. New England Journal of Medicine.2001,345(16):1147-1154.
[13] Chen S., Zhao S., White D.G., et al. Characterization of multiple-antimicrobial-resistantSalmonella serovars isolated from retail meats. Applied and environmentalmicrobiology.2004,70(1):1-7.
[14] Bielaszewska M., Mellmann A., Zhang W., et al. Characterisation of the Escherichiacoli strQain associated with an outbreak of haemolytic uraemic syndrome in Germany,2011: a microbiological study. The Lancet infectious diseases.2011.
[15] Rohde H., Qin J., Cui Y., et al. Open-source genomic analysis of shiga-toxin–producingE. coli O104: H4. New England Journal of Medicine.2011.
[16]赵悦，付萍，裴晓燕，等.中国食源性单核细胞增生李斯特菌耐药特征分析.中国食品卫生杂志.2012,1.
[17] Uyttendaele M., Busschaert P., Valero A., et al. Prevalence and challenge tests ofListeria monocytogenesin Belgian produced and retailed mayonnaise-based deli-salads,cooked meat products and smoked fish between2005and2007. International journal offood microbiology.2009,133(1):94-104.
[18]葛明，江晓，包亚慧.速冻米面制品中食源性致病菌污染调查.江苏卫生保健:学术版.2010,12(001):12-13.
[19] Bundrant B.N., Hutchins T., Bakker H.C., et al. Listeriosis outbreak in dairy cattlecaused by an unusual Listeria monocytogenes serotype4b strain. Journal of VeterinaryDiagnostic Investigation.2011,23(1):155-158.
[20] Bohaychuk V M, Gensler G E, King R K, et al. Occurrence of pathogens in raw andready-to-eat meat and poultry products collected from the retail marketplace inEdmonton, Alberta, Canada. Journal of Food Protection174.2006,69(9):2176-2182.
[21] Chasseignaux E., Gérault P., Toquin M.T., et al. Ecology of Listeria monocytogenes inthe environment of raw poultry meat and raw pork meat processing plants. FEMSmicrobiology letters.2002,210(2):271-275.
[22] Charpentier E., Courvalin P. Antibiotic Resistance in Listeriaspp. Antimicrobial agentsand chemotherapy.1999,43(9):2103-2108.
[23] S rum H., L'Abée-Lund T.M. Antibiotic resistance in food-related bacteria—a result ofinterfering with the global web of bacterial genetics. International journal of foodmicrobiology.2002,78(1):43-56.
[24] Clark C.G., Farber J., Pagotto F., et al. Surveillance for Listeria monocytogenes andlisteriosis,1995–2004. Epidemiology and infection.2010,138(04):559-572.
[25] Kümmerer K. Resistance in the environment. Journal of Antimicrobial Chemotherapy.2004,54(2):311-320.
[26] Cruchaga S., Echeita A., Aladue a A., et al. Antimicrobial resistance in salmonellaefrom humans, food and animals in Spain in1998. Journal of AntimicrobialChemotherapy.2001,47(3):315-321.
[27] Wells S.J., Fedorka-Cray P.J, Dargatz D.A., et al. Fecal shedding of Salmonella spp.by dairy cows on farm and at cull cow markets. Journal of Food Protection®.2001,64(1):3-11.
[28] Cogan T.A. Campylobacter jejuni is associated with, but not sufficient to causevibrionic hepatitis in chickens. Veterinary Microbiology.2010.
[29] H nel I., Borrmann E., Müller J., et al. Genomic and phenotypic changes ofCampylobacter jejuni strains after passage of the chicken gut. Veterinarymicrobiology.2009,136(1-2):121-129.
[30] Han K., Jang S.S., Choo E., et al. Prevalence, genetic diversity, and antibioticresistance patterns of Campylobacter jejuni from retail raw chickens inKorea. International journal of food microbiology.2007,114(1):50-59.
[31]毕水莲，李琳，唐书泽，等.变形杆菌属食物中毒的特点与防控措施.现代食品科技.2009(006):690-695.
[32] Kwon N.H., Park K.T., Jung W.K., et al. Characteristics of methicillin resistantStaphylococcus aureus isolated from chicken meat and hospitalized dogs in Koreaand their epidemiological relatedness. Veterinary microbiology.2006,117(2):304-312.
[33] Velusamy V., Arshak K., Korostynska O., et al. An overview of foodborne pathogendetection: In the perspective of biosensors. Biotechnology advances.2010,28(2):232-254.
[34] O'Brien T.F. Emergence, spread, and environmental effect of antimicrobial resistance:how use of an antimicrobial anywhere can increase resistance to any antimicrobialanywhere else. Clinical Infectious Diseases.2002,34(Supplement3): S78-S84.
[35] Khachatourians G.G. Agricultural use of antibiotics and the evolution and transfer ofantibiotic-resistant bacteria. Canadian Medical Association Journal.1998,159(9):1129-1136.
[36] Mellon M., Benbrook C., Benbrook K.L. Hogging it. Estimates of AntimicrobialAbuse in Livestock (Cambridge, MA: Union of Concerned Scientists).2001.
[37] Hendrickson H., Slechta E.S., Bergthorsson U., et al. Amplification–mutagenesis:Evidence that “directed” adaptive mutation and general hypermutability result fromgrowth with a selected gene amplification. Proceedings of the National Academy ofSciences.2002,99(4):2164.
[38] Howden B.P., Ward P.B., Charles P.G.P., et al. Treatment outcomes for seriousinfections caused by methicillin-resistant Staphylococcus aureus with reducedvancomycin susceptibility. Clinical infectious diseases.2004,38(4):521-528.
[39] Szapiel S.V., Elson N.A., Fulmer J.D., et al. Bleomycin-induced interstitialpulmonary disease in the nude, athymic mouse. The American review of respiratorydisease.1979,120(4):893.
[40] Corkill J.E., Anson J.J., Hart C.A. High prevalence of the plasmid-mediatedquinolone resistance determinant qnrA in multidrug-resistant Enterobacteriaceaefrom blood cultures in Liverpool, UK. Journal of Antimicrobial Chemotherapy.2005,56(6):1115-1117.
[41]张心如，罗宜熟，杜干英，等.动物源性耐药菌与人类安全.兽药与饲料添加剂.2004,9(003):3-6.
[42]廖龙标.水环境生物污染的分子生物学检测及其修复的初步研究[D].中国科学院研究生院(广州地球化学研究所),2006.
[43] Depardieu F., Podglajen I., Leclercq R., et al. Modes and modulations of antibioticresistance gene expression. Clinical microbiology reviews.2007,20(1):79-114.
[44] Aase B., Sundheim G., Langsrud S., et al. Occurrence of and a possible mechanismfor resistance to a quaternary ammonium compound in Listeriamonocytogenes. International journal of food microbiology.2000,62(1):57-63.
[45] Mah T.F.C., O'Toole G.A. Mechanisms of biofilm resistance to antimicrobial agents.Trends in microbiology.2001,9(1):34-39.
[46] Whitchurch C.B., Tolker-Nielsen T., Ragas P.C., et al. Extracellular DNA requiredfor bacterial biofilm formation. Science.2002,295(5559):1487.
[47] Heffron F., Mccarthy B.J., Ohtsubo H., et al. DNA sequence analysis of thetransposon Tn3: three genes and three sites involved in transposition of Tn3. Cell.1979,18(4):1153.
[48] Hall R.M., Collis C.M. Mobile gene cassettes and integrons: capture and spread ofgenes by site‐specific recombination. Molecular microbiology.1995,15(4):593-600.
[49] Hall R.M., Collis C.M., Kim M. J., et al. Mobile gene cassettes and integrons inevolution. Annals of the New York Academy of Sciences.1999,870(1):68-80.
[50] Hall R.M., Stokes H.W. Integrons or super integrons? Microbiology.2004,150(1):3-4.
[51] Hall R.M., Brookes D.E., Stokes H.W. Site‐specific insertion of genes intointegrons: role of the59‐base element and determination of the recombination cross‐over point. Molecular microbiology.1991,5(8):1941-1959.
[52] Collis C.M., Kim M.J., Partridge S.R., et al. Characterization of the class3integronand the site-specific recombination system it determines. Journal of bacteriology.2002,184(11):3017-3026.
[53] Correia M., Boavida F., Grosso F., et al. Molecular characterization of a new class3integron in Klebsiella pneumoniae. Antimicrobial agents and chemotherapy.2003,47(9):2838-2843.
[54] Léon G., Roy P.H. Excision and integration of cassettes by an integron integrase ofNitrosomonas europaea. Journal of bacteriology.2003,185(6):2036-2041.
[55] Gravel A., Messier N., Roy P.H. Point mutations in the integron integrase IntI1thataffect recombination and/or substrate recognition. Journal of bacteriology.1998,180(20):5437-5442.
[56]张翊，裴德宁. RNA干扰研究进展.中国肿瘤生物治疗杂志.2003,10(1):68-70.
[57] Ni J., Clark K.J., Fahrenkrug S.C., et al. Transposon tools hopping in vertebrates.Briefings in functional genomics&proteomics.2008,7(6):444-453.
[58] Ivics Z., Kaufman C.D., Zayed H., et al. The Sleeping Beauty transposable element:evolution, regulation and genetic applications. Current Issues in Molecular Biology.2004,6:43-56.
[59] Meng H., Zhang Z., Chen M., et al. Characterization and horizontal transfer of class1integrons in Salmonella strains isolated from food products of animal origin.International Journal of Food Microbiology.2011.
[60]顾宝柯，许学斌，金汇明，等.上海地区家畜,家禽及肉制品大肠杆菌O157: H7监测.疾病监测.2003,18(1):5-7.
[61] Robredo B., Singh K.V., Baquero F., et al. Vancomycin-resistant enterococci isolatedfrom animals and food. International journal of food microbiology.2000,54(3):197-204.
[62] Pezzotti G., Serafin A., Luzzi I., et al. Occurrence and resistance to antibiotics ofCampylobacter jejuni andCampylobacter coli in animals and meat in northeasternItaly. International journal of food microbiology.2003,82(3):281-287.
[63] Mead P.S., Slutsker L., Dietz V., et al. Food-related illness and death in the UnitedStates. Emerging infectious diseases.1999,5(5):607.
[64] Salyers A.A., Gupta A., Wang Y. Human intestinal bacteria as reservoirs forantibiotic resistance genes. Trends in microbiology.2004,12(9):412-416.
[65] Macdonald J.M., Ollinger M.E., Nelson K.E., et al. Structural change in meatindustries: implications for food safety regulation. American journal of agriculturaleconomics.1996,78(3):780-785.
[66] S rensen T.L., Blom M., Monnet D.L., et al. Transient intestinal carriage afteringestion of antibiotic-resistant Enterococcus faecium from chicken and pork. NewEngland Journal of Medicine.2001,345(16):1161-1166.
[67] Shoemaker N.B., Vlamakis H., Hayes K., et al. Evidence for Extensive ResistanceGene Transfer amongBacteroides spp. and among Bacteroides and Other Genera inthe Human Colon. Applied and Environmental Microbiology.2001,67(2):561-568.
[68] Aarestrup F.M., Seyfarth A.M., Emborg H.D., et al. Effect of abolishment of the useof antimicrobial agents for growth promotion on occurrence of antimicrobialresistance in fecal enterococci from food animals in Denmark. Antimicrobial Agentsand chemotherapy.2001,45(7):2054-2059.
[69]马永生，徐永平，金礼吉，等.饲用抗生素细菌耐药性的研究进展.中国饲料.2005(12):5-7.
[70]魏荣，王志亮.细菌耐药性基因与食品卫生安全.中国动物保健.2003(011):17-18.
[71] Blake D.P., Humphry R.W., Scott K.P., et al. Influence of tetracycline exposure ontetracycline resistance and the carriage of tetracycline resistance genes withincommensal Escherichia coli populations. Journal of applied microbiology.2003,94(6):1087-1097.
[72] Roberts M.C. Update on acquired tetracycline resistance genes. FEMS microbiologyletters.2005,245(2):195-203.
[73] Connell S.R., Trieber C.A., Dinos G.P., et al. Mechanism of Tet (O)-mediatedtetracycline resistance. The EMBO journal.2003,22(4):945-953.
[74] Recchia G.D., Hall R.M. Gene cassettes: a new class of mobile element.Microbiology.1995,141(12):3015-3027.
[75] Huovinen P., Sundstr m L., Swedberg G., et al. Trimethoprim and sulfonamideresistance. Antimicrobial agents and chemotherapy.1995,39(2):279.
[76] Sk ld O. Resistance to trimethoprim and sulfonamides. Veterinary research.2001,32(3-4):261-273.
[77] Trine M.L., S rum H. Functional Tn5393-like transposon in the R plasmid pRAS2from the fish pathogen Aeromonas salmonicida subspecies salmonicida isolated inNorway. Applied and environmental microbiology.2000,66(12):5533-5535.
[78] Yazdankhah S.P., S rum H., Oppegaard H. Comparison of genes involved inpenicillin resistance in staphylococci of bovine origin. Microbial Drug Resistance.2000,6(1):29-36.
[1] Falsafi T., Mobasheri F., Nariman F., et al. Susceptibilities to different antibiotics ofHelicobacter pylori strains isolated from patients at the pediatric medical center ofTehran, Iran[J]. Journal of clinical microbiology.2004,42(1):387-389.
[2] Chopra I., Roberts M. Tetracycline antibiotics: mode of action, applications, molecularbiology, and epidemiology of bacterial resistance[J]. Microbiology and MolecularBiology Reviews.2001,65(2):232-260.
[3]代敏，王雄清，殷桂兰.四环素耐药基因的生化和遗传机制研究进展[J].绵阳师范学院学报.2006,25(5):72-78.
[4] Mcnicholas P., Mcglynn M., Guay G.G., et al. Genetic analysis suggests functionalinteractions between the N-and C-terminal domains of the TetA (C) efflux pumpencoded by pBR322.[J]. Journal of bacteriology.1995,177(18):5355-5357.
[5] Iwaki S., Tamura N., Kimura-Someya T., et al. Cysteine-scanning mutagenesis oftransmembrane segments4and5of the Tn10-encoded metal-tetracycline/H+antiporterreveals a permeability barrier in the middle of a transmembrane water-filled channel[J].Journal of Biological Chemistry.2000,275(30):22704-22712.
[6] Someya Y., Kimura-Someya T., Yamaguchi A. Role of the Charge Interaction betweenArg70and Asp120in the Tn10-encoded Metal-Tetracycline/H+Antiporter ofEscherichia coli[J]. Journal of Biological Chemistry.2000,275(1):210-214.
[7] Doran J.L., Pang Y., Mdluli K.E., et al. Mycobacterium tuberculosis efpA encodes anefflux protein of the QacA transporter family.[J]. Clinical and diagnostic laboratoryimmunology.1997,4(1):23-32.
[8] Burdett V. Tet (M)-promoted release of tetracycline from ribosomes is GTPdependent.[J]. Journal of bacteriology.1996,178(11):3246-3251.
[9] Roberts M.C. Update on acquired tetracycline resistance genes[J]. FEMS microbiologyletters.2005,245(2):195-203.
[10] Luo H., Yousef A.E., Wang H.H. A real‐time polymerase chain reaction‐basedmethod for rapid and specific detection of spoilage Alicyclobacillus spp. in applejuice[J]. Letters in applied microbiology.2004,39(4):376-382.
[11] Wang H.H., Manuzon M., Lehman M., et al. Food commensal microbes as a potentiallyimportant avenue in transmitting antibiotic resistance genes[J]. FEMS microbiologyletters.2006,254(2):226-231.
[12]邵美丽，刘思国，尹录.单增李斯特菌四环素耐药基因tetM膜接合转移的研究[J].中国兽医科学.2010,40(006):589-592.
[13] Ethelberg S., Lisby M., Torpdahl M., et al. Prolonged restaurant‐associated outbreakof multidrug‐resistant Salmonella Typhimurium among patients from severalEuropean countries[J]. Clinical microbiology and infection.2004,10(10):904-910.
[14] Pesavento G., Ducci B., Nieri D., et al. Prevalence and antibiotic susceptibility ofListeria spp. isolated from raw meat and retail foods[J]. Food Control.2010,21(5):708-713.
[15] Yücel N., Citak S., nder M. Prevalence and antibiotic resistance of Listeria species inmeat products in Ankara, Turkey[J]. Food microbiology.2005,22(2-3):241-245.
[16] Ejim L., Farha M.A., Falconer S.B., et al. Combinations of antibiotics and nonantibioticdrugs enhance antimicrobial efficacy[J]. Nature Chemical Biology.2011,7(6):348-350.
[17] Haryani Y., Noorzaleha A.S., Fatimah A.B., et al. Incidence of Klebsiella pneumonia instreet foods sold in Malaysia and their characterization by antibiotic resistance, plasmidprofiling, and RAPD–PCR analysis[J]. Food control.2007,18(7):847-853.
[1]王丽平,陆承平,动物源性链球菌红霉素耐药基因的分布.畜牧兽医学报,2005.36(9):第977-980页.
[2]糜祖煌,黄支密,秦玲,常见球菌红霉素耐药基因研究.世界感染雜誌,2006.6(6):第517-519页.
[3]张部昌,赵志虎,马清钧,红霉素基因工程研究进展.中国生物工程杂志,2002.22(3):第40-44页.
[4] Holzbaur I.E., Ranganathan A., Thomas I.P., et al. Molecular basis of Celmer's rules:role of the ketosynthase domain in epimerisation and demonstration that ketoreductasedomains can have altered product specificity with unnatural substrates[J]. Chemistry&biology.2001,8(4):329-340.
[5] Sutcliffe J., Grebe T., Tait-Kamradt A., et al. Detection of erythromycin-resistantdeterminants by PCR.[J]. Antimicrobial Agents and Chemotherapy.1996,40(11):2562-2566.
[6] Pechère J.C. Macrolide resistance mechanisms in Gram-positive cocci[J]. Internationaljournal of antimicrobial agents.2001,18:25-28.
[7] Tait-Kamradt A., Davies T., Appelbaum P.C., et al. Two New Mechanisms ofMacrolide Resistance in Clinical Strains ofStreptococcus pneumoniae from EasternEurope and North America[J]. Antimicrobial agents and chemotherapy.2000,44(12):3395-3401.
[8] Bingen E., Leclercq R., Fitoussi F., et al. Emergence of group A streptococcus strainswith different mechanisms of macrolide resistance[J]. Antimicrobial agents andchemotherapy.2002,46(5):1199-1203.
[9] Wang H.H., Manuzon M, Lehman M, et al. Food commensal microbes as a potentiallyimportant avenue in transmitting antibiotic resistance genes[J]. FEMS microbiologyletters.2006,254(2):226-231.
[10] Eady E.A., Ross J.I., Tipper J.L., et al. Distribution of genes encoding erythromycinribosomal methylases and an erythromycin efflux pump in epidemiologically distinctgroups of staphylococci[J]. Journal of Antimicrobial Chemotherapy.1993,31(2):211-217.
[11] Roberts M.C., Sutcliffe.J, Courvalin P., et al. Nomenclature for macrolide andmacrolide-lincosamide-streptogramin B resistance determinants[J]. AntimicrobialAgents and Chemotherapy.1999,43(12):2823-2830.
[12] Poyart-Salmeron C., Carlier C., Trieu-Cuot P., et al. Transferable plasmid-mediatedantibiotic resistance in Listeria monocytogenes[J]. The Lancet.1990,335(8703):1422-1426.
[13] Okitsu N., Kaieda S., Yano H., et al. Characterization of ermB gene transposition byTn1545and Tn917in macrolide-resistant Streptococcus pneumoniae isolates[J]. Journalof clinical microbiology.2005,43(1):168-173.
[14] White D.G., Zhao S., Simjee S., et al. Antimicrobial resistance of foodbornepathogens[J]. Microbes and infection.2002,4(4):405-412.
[1] Mckinney C.W., Loftin K.A., Meyer M.T., et al. Tet and sul antibiotic resistance genesin livestock lagoons of various operation type, configuration, and antibioticoccurrence[J]. Environmental science&technology.2010.
[2]王继东，钱小毛，郁敏.大肠埃希菌连续分离株耐药性与三类整合酶基因的研究[J].世界感染杂志.2007,6(6):520-522.
[3] Sheng W.H., Ko W.J., Wang J.T., et al. Evaluation of antiseptic-impregnated centralvenous catheters for prevention of catheter-related infection in intensive care unitpatients[J]. Diagnostic microbiology and infectious disease.2000,38(1):1-5.
[4]钱秀萍，陈代杰.细菌耐药性机制的研究与新药开发Ⅳ:兽用抗菌药物与细菌耐药性及新药研究[J].国外医药:合成药.生化药.制剂分册.2001,22(6):326-329.
[5] Yun M.K., Wu Y., Li Z., et al. Catalysis and Sulfa Drug Resistance in DihydropteroateSynthase[J]. Science.2012,335(6072):1110-1114.
[6]叶金艳，祝建军，杜玉海，等.志贺菌属对复方新诺明耐药相关基因研究[J].中华医院感染学杂志.2009(002):142-144.
[7] Chen S., Zhao S., White D.G., et al. Characterization of multiple-antimicrobial-resistantSalmonella serovars isolated from retail meats[J]. Applied and environmentalmicrobiology.2004,70(1):1-7.
[8]王继东，糜祖煌，钱小毛.套式PCR法检测肺炎克雷伯菌染色体介导β-内酰胺酶基因[J].中华医院感染学杂志.2007,17(1):8-10.
[9]张嵘，蔡加昌，胡云建，等. IMP-4型金属β内酰胺酶合并膜孔蛋白OmpK36缺失引起肺炎克雷伯菌对碳青霉烯类抗生素高水平耐药[J].中华检验医学杂志.2010,33(9):845-851.
[10]黄支密，糜家睿，盛以泉，等.携带blaKPC-2型碳青霉烯酶基因泛耐药肺炎克雷伯菌医院内感染暴发的病原学分析[J].中华流行病学杂志.2010(5):559-562.
[11]黄支密，糜祖煌，邹玉秀，等.肺炎克雷伯菌中检出16S rRNA甲基化酶基因rmtB及β内酰胺酶基因blaLAP-2[J].中华检验医学杂志.2009,31(11):1268-1269.
[12] Mermel L.A. New technologies to prevent intravascular catheter-related bloodstreaminfections.[J]. Emerging infectious diseases.2001,7(2):197.
[13] McCay P.H., Ocampo-Sosa A.A., Fleming G.T.A. Effect of subinhibitoryconcentrations of benzalkonium chloride on the competitiveness of Pseudomonasaeruginosa grown in continuous culture[J]. Microbiology.2010,156(1):30-38.
[14] Huet A.A., Raygada J.L., Mendiratta K., et al. Multidrug efflux pump overexpression inStaphylococcus aureus after single and multiple in vitro exposures to biocides anddyes[J]. Microbiology.2008,154(10):3144-3153.
[1] Dice L.R. Measures of the amount of ecologic association between species[J]. Ecology.1945,26(3):297-302.
[2] Hunter P.R, Gaston M.A. Numerical index of the discriminatory ability of typingsystems: an application of Simpson's index of diversity.[J]. Journal of clinicalmicrobiology.1988,26(11):2465-2466.
[3] Ribot E.M., Fair M.A., Gautom R., et al. Standardization of pulsed-field gelelectrophoresis protocols for the subtyping of Escherichia coli O157: H7, Salmonella,and Shigella for PulseNet[J]. Foodbourne Pathogens&Disease.2006,3(1):59-67.
[4] Andrighetto C., Zampese L., Lombardi A. RAPD‐PCR characterization of lactobacilliisolated from artisanal meat plants and traditional fermented sausages of Veneto region(Italy)[J]. Letters in Applied Microbiology.2001,33(1):26-30.
[5]刘金华，贺丹，杨艳秋，等.多位点测序分型技术在病原微生物分型鉴定中的应用[J].微生物学通报.2007,34(6):1188-1191.
[6] Tenover F.C., Arbeit R.D., Goering R.V., et al. Interpreting chromosomal DNArestriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterialstrain typing.[J]. Journal of clinical microbiology.1995,33(9):2233.
[7]付英梅，马佳毓，赵月辉.脉冲凝胶电泳技术在细菌学上的应用[J].中国卫生检验杂志.1999,9(1):72-74.
[8]姜晓冰，石磊.单核细胞增生李斯特菌脉冲场凝胶电泳分型[J].食品与机械.2009(003):84-86.
[9] WHO. Risk assessment of Listeria monocytogenes in ready-to-eat foods[J].
[10]田静，刘秀梅.熟肉制品和蔬菜沙拉中单核细胞增生李斯特菌的风险分级评估[J].中华预防医学杂志.2009,43(009):781-784.
[1] Luo, Y., Xu, L., Rysz, M., et al.2005. Occurrence and transport of tetracycline,sulfonamide, quinolone, and macrolide antibiotics in the haihe river basin, China.Environmental Science and Technology19,481-487.
[2] Crecchio C., Ruggiero P., Curci M., et al.2005. Binding of DNA from Bacillus subtilison montmorillonite-humic acids-aluminum or iron hydroxypolymers: Effects ontransformation and protection against DNase. Soil Science Society of America Journal69,834-841.
[3] Zhang X.X., Zhang T Fang HHP.2009Antibiotic resistance genes in water environment.Applied Microbiology and Biotechnology82,397-414.
[4] Rysz M., Alvarez PJJ.2004Amplification and attenuation of tetracycline resistance insoil bacteria: aquifer column experiments. Water research38,3705-3712.
[5] Srum H., Labee Lund TM.2002Antibiotic resistance in food-related bacteria--a resultof interfering with the global web of bacterial genetics. International Journal of FoodMicrobiology78,43-56.
[6] Pruden A., Pei R., Storteboom H., et al. Antibiotic Resistance Genes as EmergingContaminants: Studies in Northern Colorado. Environmental Science Technology40,7445-7450.
[7] Dantas G., Sommer M., Oluwasegun R.D., et al.2008. Bacteria subsisting on antibiotics.Science320,100-104.
[8] Marraffini, L.A., Sontheimer, E.J.2008. CRISPR interference limits horizontal genetransfer in staphylococci by targeting DNA. Science322,1843-1846.
[9] Wang H., Manuzon M., Lehman M., et al.Food commensal microbes as a potentiallyimportant avenue in transmitting antibiotic resistance genes. FEMS MicrobiologyLetters2006;254:226-231.
[10] Ahmed, A.M., Shimabukuro, H., Shimamoto, T.,2009. Isolation and molecularcharacterization of multidrug-resistant strains of Escherichia coli and Salmonella fromretail chicken meat in Japan. Journal of Food Science74, M405–M410.
[11] Chen, S., Zhao, S., White, D.G., et al.2004. Characterization ofmultiple-antimicrobial-resistant Salmonella serovars isolated from retail meats. Appliedand Environmental Microbiology70,1–7.
[12] Gebreyes, W.A., Altier, C.,2002. Molecular characterization of multidrug-resistantSalmonella enterica subsp. enterica serovar typhimurium isolates from swine. Journal ofClinical Microbiology40,2813–2822.
[13] Zhao, S., Blickenstaff, K., Glenn, A., et al.2009. Beta-lactam resistance in Salmonellaisolated from retail meats in the United States National Antimicrobial ResistanceMonitoring System (NARMS):2002–2006. Applied and Environmental Microbiology75,7624–7630.
[14] Ferguson, G.C., Heinemann, J.A., Kennedy, M.A.,2002. Gene transfer betweenSalmonella enterica serovar typhimurium inside epithelial cells. Journal of Bacteriology184,2235–2242.
[15] Wang H.H., Schaffner D.W. Antibiotic resistance: how much do we know and where togo from here? Applied and Environmental Microbiology2011;9:6511-6565.
[16] Roberts M.C, Sutcliffe J., Courvalin P., et al. Nomenclature for macrolide andmacrolide-lincosamide-streptogramin B resistance determinants[J]. AntimicrobialAgents and Chemotherapy.1999,43(12):2823-2830.
[17] Hauschild T., Lüthje P., Schwarz S. Characterization of a novel type of MLS Bresistance plasmid from Staphylococcus saprophyticus carrying a constitutivelyexpressed erm(C) gene[J]. Veterinary microbiology.2006,115(1):258-263.
[18] Chopra I., Roberts M. Tetracycline antibiotics: mode of action, applications, molecularbiology, and epidemiology of bacterial resistance[J]. Microbiology and MolecularBiology Reviews.2001,65(2):232-260.
[19] Poyart C., Quesne G., Acar P., et al. Characterization of the Tn916-like transposonTn3872in a strain of Abiotrophia defectiva (Streptococcus defectivus) causingsequential episodes of endocarditis in a child[J]. Antimicrobial agents and chemotherapy.2000,44(3):790-793.
[20] Vázquez-Boland J.A., Kuhn M., Berche P., et al. Listeria pathogenesis and molecularvirulence determinants[J]. Clinical Microbiology Reviews.2001,14(3):584-64