摘要
目前全球三分之二的水产养殖品由中国生产。由于我国对水产养殖业的管制松懈，抗生素滥用的情况十分普遍。由抗生素造成的细菌耐药成为严重危害人类健康的食品安全问题。因此，深入开展和研究中国水产养殖品中耐药细菌的分布和流行情况，以及耐药基因水平转移的分子机制的分析是十分必要，并且可以为食品安全措施的实施对象和实施方向提供数据上的支持。
本研究以广州市上水产养殖品作为研究对象，对水产养殖品中耐药菌数量、耐药表型、耐药基因型和耐药基因水平转移的机理进行研究，采用菌落计数、抗生素最小抑制浓度检测以及通过聚合酶链式反应和16SrRNA测序研究水产养殖品中耐药共生菌的耐药水平，分析耐药决定因子和耐药菌菌体类型。最后，应用化学转化技术和菌体传代实验分析耐药质粒的水平传播和耐药稳定性的机制。论文主要成果如下：（1）水产养殖品中含有大量多耐药共生菌，说明水产养殖品是耐药菌发展扩大和传播的潜在的途径。在主要研究的505株多重耐药细菌中，约有四分之一的多重耐药细菌含有一型整合子整合酶基因intI以及耐磺胺药物的sul1基因。15%的多重耐药菌含有耐磺胺药物的sul2基因,5%的多重耐药菌含有抗四环素的tetE基因。β内酰胺酶编码的抗性基因blaTEM,blaCMY,以及抗红霉素的耐药基因ermB和ermC在多重耐药细菌中的分布比率分别为4.5%,1.7%,1.3%以及0.3%。（2）在本文选取的多重耐药菌中，从产品蛋白胨水洗涤液和内脏样品中分离到的多重耐药细，经过鉴定后发现大肠杆菌和气单胞菌是广州市海鲜产品中多耐药基因的主要宿主菌体。（3）多耐药质粒具有十分稳定的遗传能力，在非选择性环境中仍然可以不断地遗传给子代细菌，并表现出和母代细菌相同的耐药表型和耐药水平，并且多耐药质粒通过水平转移可以向新的宿主菌体转化。
Close to2/3of the aquaculture products are produced in China where regulatory controlsare weak and antibiotics are often abused. The rapid emergence of antibiotic-resistant (ART)bacteria has been a major public health concern. Studies are needed to examine theprevalence of antibiotic resistant bacteria associated with aquaculture products and thedissemination of antibiotic resistant gene. The study will provide basic research data andimformation for the establish of food safety control.
The current study examined the prevalence of antibiotic resistant (ART) bacteria andantibiotic resistance (AR) genes in several aquaculture products from retail markets inGuangzhou, China. Resistant bacteria to representative antibiotics were screened on selectivemedia supplemented with the corresponding drugs. Representative AR genes in these isolates,as well as the identities of the AR gene carriers were determined by PCR and16S rRNAsequence analysis. AR persistence, mobility and profiles were further characterized inselected resistant isolates. The results showed that (1) ART commensal bacteria were foundin100%of the products examined. Among505multi-drug resistant isolates examined, closeto contained the class1integrase-encoding and sul1genes,15%contained sul2, and5%with tet(E). Incidence of β-lactamase-encoding genes blaTEM, blaCMY, as well aserythromycin resistance determinants ermB and ermC were4.5%,1.7%, and1.3%and0.3%,respectively.(2) Most of the ART isolates identified from rinsing water and intestines wereAeromonas sp. and Enterobacter sp., respectively.(3) Plasmid-associated class1integraseand AR encoding genes were identified in several ART isolates by Southern hybridization.Three multi-drug resistance encoding plasmids were transferred into Escherichia coli DH5αby chemical transformation and led to acquired AR in the transformants. In addition, the ARtraits in many isolates were quite stable, even in the absence of the selective pressure.
引文
[1] Dack G.M. Food-borne infections and intoxications [J]. American Journal of PublicHealth and the Nations Health,1953,43(9):1180-1181
[2] Pederson C.S. Microbiology of food fermentations [M]. Second Edition,Westport/Connecticut (USA), The AVI Publishing Company, Inc.,1979:384
[3] Jay J. Modern food microbiology [M].7thedition, Kluwer Academic/Plenum: New York,Springer,2005:790
[4] Doyle M.P., Beuchat L.R., and Montville T.J. Food microbiology: fundamentals andfrontiers [M].3rd Edition, Washington DC, ASM Press,1997
[5] McCaig L.F., Besser R.E., and Hughes J.M. Antimicrobial-drug prescription inambulatory care settings, United States,1992–2000[J]. Emerging Infectious Diseases,2003,9(4):432
[6] Lehman M., Assessment of antibiotic resistant commensal bacteria in food [D].http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html&identifier=ADA455898,2006
[7] Serrano P.H., Responsible use of antibiotics in aquaculture [M].http://www.fao.org/fi/oldsite/eims_search/1_dett.asp?calling=simple_s_result&lang=en&pub_id=169760,2005
[8] Doyle M.E., Alternatives to antibiotic use for growth promotion in animal husbandry [Z].http://fri.wisc.edu/docs/pdf/antibiot.pdf,2001
[9]冯新,韩文瑜,雷连成.细菌对四环素类抗生素的耐药机制研究进展[J].中国兽药杂志,2004,2:38-42
[10] Chopra I. and Roberts M. Tetracycline antibiotics: mode of action, applications,molecular biology, and epidemiology of bacterial resistance [J]. Microbiology andMolecular Biology Reviews,2001,65(2):232-260
[11] Sk ld O. Sulfonamide resistance: mechanisms and trends [J]. Drug Resistance Updates,2000,3(3):155-160
[12] USP, Sulphonamides. Drugs for Animal Use [Z].http://www.usp.org/veterinary/monographs/sulfonamides.pdf,2000i
[13]USP, Macrolides. Veterinary Medicine [Z].http://www.usp.org/veterinary/monographs/macrolides.htm,2000c
[14] Periti P., Mazzei T. and Mini E., et al. Pharmacokinetic drug interactions of macrolides[J]. Clinical pharmacokinetics,1992,23(2):106
[15] Pharmacopoeia, U.U.S., Cephalosporins [Z].http://www.usp.org/veterinary/monographs/cephalosporins.htm.1999
[16] USP, Penicillin G. Veterinary Medicine [Z].http://www.usp.org/veterinary/monographs/penicilling.htm,2000a
[17] USP, Aminoglycosides. Drugs for Animal Use [Z].http://www.usp.org/veterinary/monographs/aminoglycosides.pdf,2000l
[18] USP Spectinomycin. Veterinary Medicine [Z].http://www.usp.org/veterinary/monographs/spectinomycin.htm.2000d
[19] Tacon A.G.J. and Forster I.P. Aquafeeds and the environment: policy implications [J].Aquaculture,2003,226(1-4):181-189
[20] USP, Enrofloxacin. Veterinary Medicine [Z].http://www.usp.org/veterinary/monographs/enrofloxacin.htm2000h
[21] USP, Sarafloxacin. Drugs for Animal Use Veterinary-Systemic [Z].http://www.usp.org/veterinary/monographs/sarafloxacin.pdf,2000m
[22] USP, Lincosamides. Drugs for Animal Use [Z].http://www.usp.org/veterinary/monographs/lincosamides.pdf,2000j
[23] USP, Rifampin. Drugs for animal use [Z].http://www.usp.org/veterinary/monographs/rifampin.pdf,2000k
[24] Anderson A.D., Nelson M. and Baker N.L. Public health consequences of use ofantimicrobial agents in agriculture [J]. Food Safety Assurance and Veterinary PublicHealth,2002,3:173
[25] Fries R. Conclusions and activities of previous expert groups: the scientific steeringcommittee of the EU [J]. Journal of Veterinary Medicine,2004,51:403–407
[26] WHO, WHO Global Principless for the containment of antimicrobial resistance inanimals treated for food: report of a WHO [R].http://online.liebertpub.com/doi/abs/10.1089/107662903322762815,2000
[27]张永信.抗生素的合理使用[J].中华儿科杂志,2002,40(8):450-452
[28]沈叙庄.关注对动物使用抗生素与细菌耐药的问题[J].中华儿科杂志,2002,40(8):452-453
[29] White D.G., Zhao S., Simjee S., et al. Antimicrobial resistance of foodborne pathogens[J]. Microbes and infection,2002,4(4):405-412
[30] Andremont A. Commensal flora may play key role in spreading antibiotic resistance [J].ASM news,2003,69:601-607
[31] Dewey C.E., Cox B.D., Straw B.E., et al. Associations between off-label feed additivesand farm size, veterinary consultant use, and animal age [J]. Preventive VeterinaryMedicine,1997,31(1):133-146
[32] FDA, National Antimicrobial resistance monitoring system (NARMS): enteric bacteria
[Z]. http://www.cdc.gov/narms/,2005
[33] Bywater R., Deluyker H., Deroover E., et al. A european survey of antimicrobialsusceptibility among zoonotic and commensal bacteria isolated from food-producinganimals [J]. Journal of Antimicrobial Chemotherapy,2004,54(4):744-754
[34] Johnston L.M. and Jaykus L.A. Antimicrobial resistance of Enterococcus speciesisolated from produce [J]. Applied and Environmental Microbiology,2004,70(5):3133-3137
[35] Scott H., Campbell LD., Harvey RB., et al. Patterns of antimicrobial resistance amongcommensal Escherichia coli isolated from integrated multi-site housing and workercohorts of humans and swine [J]. Foodborne Pathogens&Disease,2005,2(1):24-37
[36] Mead P.S., Slutsker L., Dietz V., et al. Food-related illness and death in the UnitedStates[J]. Emerging Infectious Diseases,1999,5(5):607
[37] Schmidt C.W. Antibiotic resistance in livestock: more at stake than steak [J].Environmental Health Perspectives,2002,110(7): A396
[38] White D.G., Zhao S., Sudler R.., et al. The isolation of antibiotic-resistant Salmonellafrom retail ground meats [J]. New England Journal of Medicine,2001.345(16):1147-1154
[39] Harwood V.J., Brownell M., Perusek W., et al. Vancomycin-resistant Enterococcus spp.isolated from wastewater and chicken feces in the United States [J]. Applied andEnvironmental Microbiology,2001,67(10):4930-4933
[40] Huys G., Gevers D., Temmerman R., et al. Comparison of the antimicrobial tolerance ofoxytetracycline-resistant heterotrophic bacteria isolated from hospital sewage andfreshwater fishfarm water in Belgium [J]. Systematic and Applied Microbiology,2001,24(1):122-130
[41] DeFrancesco K.A., Cobbold R.N., Rice D.H., et al. Antimicrobial resistance ofcommensal Escherichia coli from dairy cattle associated with recent multi-resistantsalmonellosis outbreaks [J]. Veterinary Microbiology,2004,98(1):55-61
[42] Mathur S. and Singh R. Antibiotic resistance in food lactic acid bacteria—a review [J].International Journal of Food Microbiology,2005,105(3):281-295
[43] 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
[44] Franklin A., Acar J., Anthony F., et al. Antimicrobial resistance: harmonization ofnational antimicrobial resistance monitoring and surveillance programmers in animalsand in animal-derived food [J]. Revue Scientifique et Technique (International Office ofEpizootics),2001,20(3):859
[45]Eaton T.J. and Gasson M.J. Molecular screening of Enterococcus virulence determinantsand potential for genetic exchange between food and medical isolates [J]. Applied andEnvironmental Microbiology,2001,67(4):1628-1635
[46] Marshall B.M., Ochieng D.J. and Levy S.B. Commensals: underappreciated reservoir ofantibiotic resistance [J]. Microbe,2009.4:231-238
[47] Ready D., Bedi R., Spratt D.A., et al. Prevalence, proportions, and identities ofantibiotic-resistant bacteria in the oral microflora of healthy children [J]. Microbial DrugResistance,2003,9(4):367-372
[48] Cui S., Ge B., Zheng J., et al. Prevalence and antimicrobial resistance of Campylobacterspp. and Salmonella serovars in organic chickens from Maryland retail stores [J].Applied and Environmental Microbiology,2005,71(7):4108-4111
[49] Mathew A.G., Cissell R. and Liamthong S. Antibiotic resistance in bacteria associatedwith food animals: a United States perspective of livestock production [J]. FoodbornePathogens and Disease,2007,4(2):115-133
[50] Simjee S., White DG., Wagner D.D., et al. Identification of vat (E) in Enterococcusfaecalis isolates from retail poultry and its transferability to Enterococcus faecium [J].Antimicrobial Agents and Chemotherapy,2002,46(12):3823-3828
[51] Yang B., Qu D., Zhang X., et al. Prevalence and characterization of Salmonella serovarsin retail meats of marketplace in Shaanxi, China [J]. International Journal of FoodMicrobiology,2010,141(1):63-72
[52] Zhang Y., Yeh E., Hall G., et al. Characterization of Listeria monocytogenes isolatedfrom retail foods [J]. International Journal of Food Microbiology,2007,113(1):47-53
[53] Zhao C., Ge B., De Villena J., et al. Prevalence of Campylobacter spp., Escherichia coli,and Salmonella serovars in retail chicken, turkey, pork, and beef from the GreaterWashington, DC, area [J]. Applied and Environmental Microbiology,2001,67(12):5431-5436
[54] Duran G.M. and Marshall D.L. Ready-to-eat shrimp as an international vehicle ofantibiotic-resistant bacteria [J]. Journal of Food Protection,2005,68(11):2395-2401
[55] Li X. and Wang H.H. Tetracycline resistance associated with commensal bacteria fromrepresentative ready-to-consume deli and restaurant foods [J]. Journal of FoodProtection,2010,73(10):1841-1848
[56] Moriarty D.J.W. Disease control in shrimp aquaculture with probiotic bacteria [J].Microbial Interactions in Aquaculture,1999
[57] Austin, B. and Austin D.A. Bacterial fish pathogens: disease of farmed and wild fish [M].4th edition. Springer Verlag,1999:552pages
[58]李爱华.水产养殖中使用的抗菌药物及细菌耐药性[J].中国水产科学,2002,9(1):87-91
[59]佚名.中外允许使用的渔药种类对比[Z].http://www.gdfs.gov.cn/rdgz/ShowArticle.asp?ArticleID=20504,2008
[60] Snieszko S. F. Control of furunculosis in rainbow trout [J]. U S Fish and WildfishService,1957,125(10):555-564
[61] Aoki T.E., Yada C. Studies of the drug resistance of fish-pathogenic bacteria [J].Japanese Journal of Microbiology,1972,16(3):233-238
[62] Aoki T, Kitao T. Multiple drug resistant plasmids from E. tarda in eel culture ponds [J].Bulletin of the Japanese Society for the Science of Fish198753(10):1821-1825
[63] Starliper C.E., Cooper R.K., Shotts Jr E.B., et al. Plasmid-mediated Romet resistance ofEdwardsiella ictaluri [J]. Journal of Aquatic Animal Health,1993,5(1):1-8
[64] Clark C., Kravetz A.N., Alekseenko V.V., et al. Microbiological and epidemiologicalinvestigation of cholera epidemic in Ukraine during1994and1995[J]. Epidemiologyand Infection,1998,121(01):1-13
[65] Furushita M., Shiba T., Maeda T., et al. Similarity of tetracycline resistance genesisolated from fish farm bacteria to those from clinical isolates [J]. Applied andEnvironmental Microbiology,2003,69(9):5336-5342
[66] Guglielmetti E., Korhonen J.M., Heikkinen J., et al. Transfer of plasmid‐mediatedresistance to tetracycline in pathogenic bacteria from fish and aquaculture environments[J]. FEMS Microbiology Letters,2009,293(1):28-34
[67] Alcaide E., Blasco M.D. and Esteve C. Occurrence of drug-resistant bacteria in twoEuropean eel farms [J]. Applied and Environmental Microbiology,2005,71(6):3348-3350
[68] Kim S.R., Nonaka L., and Suzuki S. Occurrence of tetracycline resistance genes tet (M)and tet (S) in bacteria from marine aquaculture sites [J]. FEMS Microbiology Letters,2004,237(1):147-156
[69] Kadlec K., von Czapiewski E., Kaspar H., et al. Molecular basis of sulfonamide andtrimethoprim resistance in fish-pathogenic Aeromonas isolates [J]. Applied andEnvironmental Microbiology,2011,77(20):7147-7150
[70] Dang H., Song L., Chen M., et al. Concurrence of cat and tet genes in multipleantibiotic-resistant bacteria isolated from a sea cucumber and sea urchin mariculturefarm in China [J]. Microbial Ecology,2006,52(4):634-643
[71] FAO, The state of world fisheries and aquaculture [R].http://www.fao.org/docrep/013/i1820e/i1820e.pdf.,2010
[72] FAO, Aquaculture in China and Asia [R].http://www.fao.org/newsroom/common/ecg/1000565/en/factsheet.pdf,2007
[73] Tsoumas A, Aoderman D J, Rodgers C J. Aeromonas salmonicida: development ofresistance to42quinoline antimicrobials [J]. Journal of Fish Disease,198912(5):493-507
[74] Pedersen K., Tiainen T, and Larsen J. Antibiotic resistance of Vibrio anguillarum, inrelation to serovar and plasmid contents [J]. Acta Veterinaria Scandinavica,1995,36(1):55
[75] Aoki T, K.T., Changes in drug resistance of V ibrio anguillarum in cultured ayu inJapan [J]. Journal of Fish Disease,1981,4(2):223-230
[76]陈军昌,于莉.腐败假单胞菌人工感染河蟹的毒性试验及药物敏感性实验[J].水产科学,1999,18(2):18-20
[77] Aoki T., Kanazawa T., and Kitao T. Epidemiological surveillance of drug resistantVibrio anguillarum strains [isolated from diseased ayu Plecoglossus altivelis in variousareas of Japan][J]. Fish Pathology,1985,20:199-208
[78] Aoki T. and Kitao T. Drug resistance and transferable R plasmids in Edwardsiella tardafrom fish culture ponds (魚病に関する国際セミナ-)[J].魚病研究,1981,15(3):277-281
[79] Dixon B., Yamashita J., and Evelyn F. Antibiotic resistance of Aeromonas spp. isolatedfrom tropical fish imported from Singaporem [J]. Journal of Aquatic Animal Health,1990,2(4):295-297
[80]马永生.饲用抗生素细菌耐药性的研究进展[J].中国饲料,2005(12):5-7
[81]邢玉斌,吴晓东,陈世平.细菌的耐药性[J].中华医院感染学杂志,2002.12(9):718-720
[82]党京丹,细菌耐药机制研究新进展[J].临床和实验医学杂志,2009,8(009):134-135
[83]糜祖煌,细菌耐药的分子机制[J].临床儿科杂志,2005,23(007):422-424
[84]孙忠实,细菌耐药性与临床干预[J].药物不良反应杂志,2003,5(3):151-155
[85] Helinski D.R. Plasmid determined resistance to antibiotics: molecular properties of Rfactors [J]. Annual Reviews in Microbiology,1973.27(1):437-470
[86]Mitsuhashi S. The R factors [J]. The Journal of Infectious Diseases,1969:89-100.
[87] Watanabe T. Infective heredity of multiple drug resistance in bacteria [J].Bacteriological Reviews,1963,27(1):87
[88] Jacob F. and Wollman E.L. Sexuality and the genetics of bacteria [M]. First edition,New York, Academic Press,1961
[89] Cohen S.N., Chang A.C.Y., and Hsu L. Nonchromosomal antibiotic resistance inbacteria: genetic transformation of Escherichia coli by R-factor DNA [J]. Proceedings ofthe National Academy of Sciences,1972.69(8):2110
[90] Stock J.B., Stock A.M., and Mottonen J.M. Signal transduction in bacteria [J]. Nature,1990,344(6265):395
[91] Ploy M.C., Lambert T., Couty J.P., et al. Integrons: an antibiotic resistance gene captureand expression system [J]. Clinical Chemistry and Laboratory Medicine,2005,38(6):483-487
[92] Poyart C., Pierre C., Quesne G., et al. Emergence of vancomycin resistance in the genusStreptococcus: characterization of a vanB transferable determinant in Streptococcusbovis [J]. Antimicrobial Agents and Chemotherapy,1997.41(1):24-29
[93] Sundaresan V. Horizontal spread of transposon mutagenesis: new uses for old elements[J]. Trends in Plant Science,1996,1(6):184-190
[94] J rg Kunte H. and Galinski E.A. Transposon mutagenesis in halophilic eubacteria:conjugal transfer and insertion of transposon Tn5and Tn1732in Halomonas elongate [J].FEMS Microbiology Letters,1995,128(3):293-299
[95] Roberts A.P., Pratten J. Wilson M., et al. Transfer of a conjugative transposon, Tn5397in a model oral biofilm [J]. FEMS Microbiology Letters,1999,177(1):63-66
[96] Hall R.M., Collis C. M., Kim M. I. J., et al. Mobile gene cassettes and integrons inevolution [J]. Annals of the New York Academy of Sciences,1999,870(1):68-80
[97] Hall R.M. and Collis C.M., Mobile gene cassettes and integrons: capture and spread ofgenes by site‐specific recombination [J]. Molecular Microbiology,1995,15(4):593-600
[98] Hall R., Brookes D., and Stokes H. Site‐specific insertion of genes into integrons: roleof the59‐base element and determination of the recombination cross‐over point.Molecular Microbiology [J],1991,5(8):1941-1959
[99]刘利强,杜娟,刘彦威.细菌耐药性的分子机制[J].动物医学进展,2006,27(10):47-50
[100] Collis C.M., Kim M. J., Partridge S. R., et al. Characterization of the class3integronand the site-specific recombination system it determines [J]. Journal of Bacteriology,2002,184(11):3017-3026
[101] Correia M., Boavida F., Grosso F., et al., Molecular characterization of a new class3integron in Klebsiella pneumonia [J]. Antimicrobial Agents and Chemotherapy,2003,47(9):2838-2843
[102] McDonald L.C., Rossiter S., Mackinson C., et al. Quinupristin-dalfopristin–resistantEnterococcus faecium on chicken and in human stool specimens [J]. New EnglandJournal of Medicine,2001,345(16):1155-1160
[103] Recchia G.D. and Hall R.M. Gene cassettes: a new class of mobile element [J].Microbiology,1995,141(12):3015-3027
[104] Weldhagen G.F. Integrons and beta-lactamases-a novel perspective on resistance [J].International Journal of Antimicrob Agents,2004,23:556-562
[105]Walsh T.R.,The emergence and implications of metallo-beta-lactamases ingram-negative bacteria [J]. Clinical Microbiology and Infection,2005,11:2-9
[106] Depardieu F., Podglajen I., Leclercq, R., et al. Modes and modulations of antibioticresistance gene expression [J]. Clinical Microbiology Reviews,2007,20(1):79-114
[107] Collis C.M. and Hall R.M. Comparison of the structure–activity relationships of theintegron-associated recombination sites attI3and attI1reveals common features [J].Microbiology,2004,150(5):1591-1601
[108] Chiristina M.C., M.-J.K., Stokes H.W., et al. Integron-encoded intI integrasespreferentially recognize the adjacent attI cognate site in recombination with a59-be site[J]. Molecular Microbiology,2002,46(5):1415-1427
[109] Segal H., Francia M., Lobo J. M. G., et al. Reconstruction of an active integronrecombination site after integration of a gene cassette at a secondary site [J].Antimicrobial Agents and Chemotherapy,1999,43(10):2538-2541
[110] Collis C.M., Recchia G. D., Kim M. J., et al. Efficiency of recombination reactionscatalyzed by class1integron integrase IntI1[J]. Journal of Bacteriology,2001,183(8):2535-2542
[111] Partridge S.R., R.G.D., Scaramuzzi C., et al. Definition of the attIl site of class1integrons [J]. Microbiology,2000,146(11):2855-2864
[112] Denis C., Poirel L., Carricajo A., et al. Nosocomial transmission of NDM‐1‐producing Escherichia coli within a non‐endemic area in France [J]. ClinicalMicrobiology and Infection,2012,18(5):128-130
[113] Oteo J., Domingo-García D., Fernández-Romero S., et al. Abdominal abscess due toNDM-1-producing Klebsiella pneumoniae in Spain [J]. Journal of Medical Microbiology,2012
[114] Stanton T.B., Humphrey S.B., and Stoffregen W.C. Chlortetracycline-resistantintestinal bacteria in organically raised and feral swine [J]. Applied and EnvironmentalMicrobiology,2011,77(20):7167-7170
[115] Hayes F. Toxins-antitoxins: plasmid maintenance, programmed cell death, and cellcycle arrest [J]. Science,2003,301(5639):1496-1499
[116] Kruse H., Sorum H., Tenover F.C., et al. A transferable multiple drug resistanceplasmid from Vibrio cholerae O1[J]. Microbial Drug Resistance,1995,1(3):203-210
[117] Luo N., Pereira S., Sahin O., et al. Enhanced in vivo fitness offluoroquinolone-resistant Campylobacter jejuni in the absence of antibiotic selectionpressure [J]. Proceedings of the National Academy of Sciences of the United States ofAmerica,2005,102(3):541-546
[118] Zhang L., Kinkelaar D., Huang Y., et al. Acquired antibiotic resistance: are we bornwith it [J]? Applied and Environmental Microbiology,2011,77(20):7134-7141
[119] Chen S., Zhao S., White D. G., et al. Characterization ofmultiple-antimicrobial-resistant Salmonella serovars isolated from retail meats [J].Applied and Environmental Microbiology,2004,70(1):1-7
[120] Malhotra-Kumar S., Lammens C., Piessens J., et al. Multiplex PCR for simultaneousdetection of macrolide and tetracycline resistance determinants in streptococci [J].Antimicrobial Agents and Chemotherapy,2005,49(11):4798-4800
[121] Kozak G. K., Boerlin P., Janecko N., et al. Antimicrobial resistance in Escherichia coliisolates from swine and wild small mammals in the proximity of swine farms and innatural environments in Ontario, Canada [J]. Applied and Environmental Microbiology,2009,75(3):559-566
[122] Dallenne C., Da Costa A., Decre D., et al. Development of a set of multiplex PCRassays for the detection of genes encoding important β-lactamases inEnterobacteriaceae [J]. Journal of Antimicrobial Chemotherapy,2010,65(3):490-495
[123] Zhao S., White D. G., McDermott P. F. Identification and Expression ofCephamycinasebla CMY Genes in Escherichia coliand Salmonella Isolates from FoodAnimals and Ground Meat [J]. Antimicrobial Agents and Chemotherapy,2001,45(12):3647-3650
[124] Mugnaioli C., Luzzaro F., De Luca F., et al. CTX-M-type extended-spectrumβ-lactamases in Italy: molecular epidemiology of an emerging countrywide problem[J]. Antimicrobial Agents and Chemotherapy,2006,50(8):2700-2706