General discussion
6. General conclusion
The results of this Ph.D. thesis showed that porcine B. bronchiseptica isolates carry resistance genes on mobile genetic elements. Some of the identified resistance genes or similar genes have been described in Enterobacteriaceae, but most of them not yet in porcine respiratory tract pathogens. In conclusion this study showed, that porcine B. bronchiseptica isolates carry resistance genes on large conjugative plasmids. Horizontal transfer to a different species was shown, the plasmids replicated in E. coli and conferred resistance to the recipients. The resistance genes harboured by B. bronchiseptica were identical or similar to isolates from the gastro-intestinal tract or from the environment, but differed from the resistance genes occurring in Pasteurellaceae. Based on the mobile character of the identified resistance genes, it is likely that B. bronchiseptica has acquired these genes from enterobacterial hosts, in which these genes commonly occur.
References
1. Adrian PV, Thomson CJ, Klugman KP, Amyes SG. New gene cassettes for trimethoprim resistance, dfr13, and Streptomycin-spectinomycin resistance, aadA4, inserted on a class 1 integron. Antimicrob Agents Chemother 2000; 44: 355-61.
2. Ahmed AM, Nakano H, Shimamoto T. Molecular characterization of integrons in non-typhoid Salmonella serovars isolated in Japan: description of an unusual class 2 integron. J Antimicrob Chemother 2005; 55:
371-4.
3. Allmeier H, Cresnar B, Greck M, Schmitt R. Complete nucleotide sequence of Tn1721: gene organization and a novel gene product with features of a chemotaxis protein. Gene 1992; 111: 11-20.
4. Altrock A von. [Occurrence of bacterial agents in lungs of pigs and evaluation of their resistance to antibiotics]. Berl Münch Tierärztl Wochenschr 1998; 111: 164-172.
5. Antunes P, Machado J, Sousa JC, Peixe L. Dissemination amongst humans and food products of animal origin of a Salmonella typhimurium clone expressing an integron-borne OXA-30 beta-lactamase. J Antimicrob Chemother 2004; 54: 429-34.
6. Appelbaum PC, Tamim J, Pankuch GA, Aber RC. Susceptibility of 324 nonfermentative gram-negative rods to 6 cephalosporins and azthreonam. Chemotherapy 1983; 29: 337-44.
7. Appelbaum PC, Tamim J, Stavitz J, Aber RC, Pankuch GA. Sensitivity of 341 non-fermentative gram-negative bacteria to seven beta-lactam antibiotics. Eur J Clin Microbiol 1982; 1: 159-65.
8. Bartkus JM, Juni BA, Ehresmann K, Miller CA, Sanden GN, Cassiday PK, Saubolle M, Lee B, Long J, Harrison AR, Jr., Besser JM. Identification of a mutation associated with erythromycin resistance in Bordetella pertussis: implications for surveillance of antimicrobial resistance. J Clin Microbiol 2003; 41:
1167-72.
9. Baucheron S, Tyler S, Boyd D, Mulvey MR, Chaslus-Dancla E, Cloeckaert A. AcrAB-TolC directs efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium DT104. Antimicrob Agents Chemother 2004; 48: 3729-35.
10. Berger-Bachi B. Genetic basis of methicillin resistance in Staphylococcus aureus. Cell Mol Life Sci 1999;
56: 764-70.
11. Binder S, Le NB, Berner H, Bauer J. [The effectiveness of tilmicosin in respiratory diseases of swine]. Berl Münch Tierärztl Wochenschr 1993; 106: 6-9.
12. Bischoff KM, White DG, Hume ME, Poole TL, Nisbet DJ. The chloramphenicol resistance gene cmlA is disseminated on transferable plasmids that confer multiple-drug resistance in swine Escherichia coli. FEMS Microbiol Lett 2005; 243: 285-91.
13. Blanco M, Gutierrez-Martin CB, Rodriguez-Ferri EF, Roberts MC, Navas J. Distribution of tetracycline resistance genes in Actinobacillus pleuropneumoniae isolates from Spain. Antimicrob Agents Chemother 2006; 50: 702-8.
14. Bozdogan B, Tristram S, Appelbaum PC. Combination of altered PBPs and expression of cloned extended-spectrum beta-lactamases confers cefotaxime resistance in Haemophilus influenzae. J Antimicrob Chemother 2006; 57: 747-9.
15. Bradford PA. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev 2001; 14: 933-51.
16. Braibant M, Chevalier J, Chaslus-Dancla E, Pages JM, Cloeckaert A. Structural and functional study of the phenicol-specific efflux pump FloR belonging to the major facilitator superfamily. Antimicrob Agents Chemother 2005; 49: 2965-71.
17. Brockmeier S, Halbur P, Thacker E. Porcine respiratory disease complex. In: Brogden KA, Guthmiller JM, eds. Polymicrobial Diseases. Washington DC: ASM Press, 2002; 231-58.
General discussion chapter 7
18. Burton PJ, Thornsberry C, Cheung Yee Y, Watts JL, Yancey RJ, Jr. Interpretive criteria for antimicrobial susceptibility testing of ceftiofur against bacteria associated with swine respiratory disease. J Vet Diagn Invest 1996; 8: 464-8.
19. Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 1995; 39: 1211-33.
20. Butaye P, Cloeckaert A, Schwarz S. Mobile genes coding for efflux-mediated antimicrobial resistance in Gram-positive and Gram-negative bacteria. Int J Antimicrob Agents 2003 ; 22: 205-10.
21. Cagliero C, Mouline C, Payot S, Cloeckaert A. Involvement of the CmeABC efflux pump in the macrolide resistance of Campylobacter coli. J Antimicrob Chemother 2005; 56: 948-50.
22. Carattoli A. Importance of integrons in the diffusion of resistance. Vet Res 2001; 32: 243-59.
23. Chiou CS, Jones AL. Nucleotide sequence analysis of a transposon (Tn5393) carrying streptomycin resistance genes in Erwinia amylovora and other gram-negative bacteria. J Bacteriol 1993; 175: 732-40.
24. Chollet R, Chevalier J, Bryskier A, Pages JM. The AcrAB-TolC pump is involved in macrolide resistance but not in telithromycin efflux in Enterobacter aerogenes and Escherichia coli. Antimicrob Agents Chemother 2004; 48: 3621-4.
25. Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev 2001; 65: 232-60
26. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals - Second edition: Approved standard - 2nd edition.
CLSI document M31-A2. CLSI, Wayne, PA, USA, 2002.
27. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals; informational supplement M31-S31. CLSI, Wayne, PA, USA, 2002.
28. Cloeckaert A, Baucheron S, Flaujac G, Schwarz S, Kehrenberg C, Martel JL, Chaslus-Dancla E. Plasmid-mediated florfenicol resistance encoded by the floR gene in Escherichia coli isolated from cattle.
Antimicrob Agents Chemother 2000; 44: 2858-60.
29. Coleman DC, Chopra I, Shales SW, Howe TG, Foster TJ. Analysis of tetracycline resistance encoded by transposon Tn10: deletion mapping of tetracycline-sensitive point mutations and identification of two structural genes. J Bacteriol 1983; 153: 921-9.
30. DeRosa DC, Veenhuizen MF, Bade DJ, Shryock TR. In vitro susceptibility of porcine respiratory pathogens to tilmicosin. J Vet Diagn Invest 2000; 12: 541-6.
31. Doublet B, Schwarz S, Kehrenberg C, Cloeckaert A. Florfenicol resistance gene floR is part of a novel transposon. Antimicrob Agents Chemother 2005; 49: 2106-8.
32. Fournier PE, Vallenet D, Barbe V, Audic S, Ogata H, Poirel L, Richet H, Robert C, Mangenot S, Abergel C, Nordmann P, Weissenbach J, Raoult D, Claverie JM. Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet 2006; 2: e7.
33. Frech G, Schwarz S. Molecular analysis of tetracycline resistance in Salmonella enterica subsp. enterica serovars Typhimurium, Enteritidis, Dublin, Choleraesuis, Hadar and Saintpaul: construction and application of specific gene probes. J Appl Microbiol 2000; 89: 633-41.
34. Frech G, Schwarz S. Plasmid-encoded tetracycline resistance in Salmonella enterica subsp. enterica serovars choleraesuis and typhimurium: identification of complete and truncated Tn1721 elements. FEMS Microbiol Lett 1999; 176: 97-103.
35. Gaze WH, Abdouslam N, Hawkey PM, Wellington EM. Incidence of class 1 integrons in a quaternary ammonium compound-polluted environment. Antimicrob Agents Chemother 2005; 49: 1802-7.
36. Gebreyes WA, Altier C. Molecular characterization of multidrug-resistant Salmonella enterica subsp.
enterica serovar Typhimurium isolates from swine. J Clin Microbiol 2002; 40: 2813-22.
37. Graham AC, Abruzzo GK. Occurrence and characterization of plasmids in field isolates of Bordetella bronchiseptica. Am J Vet Res 1982; 43: 1852-5.
38. Gutierrez-Martin CB, del Blanco NG, Blanco M, Navas J, Rodriguez-Ferri EF. Changes in antimicrobial susceptibility of Actinobacillus pleuropneumoniae isolated from pigs in Spain during the last decade. Vet Microbiol 2006; 115: 218-22.
39. Hammerum AM, Sandvang D, Andersen SR, Seyfarth AM, Porsbo LJ, Frimodt-Moller N, Heuer OE.
Detection of sul1, sul2 and sul3 in sulphonamide resistant Escherichia coli isolates obtained from healthy humans, pork and pigs in Denmark. Int J Food Microbiol 2006; 106: 235-7.
40. Harada K, Asai T, Kojima A, Ishihara K, Takahashi T. Role of coresistance in the development of resistance to chloramphenicol in Escherichia coli isolated from sick cattle and pigs. Am J Vet Res 2006; 67:
230-5.
41. Heuer C, Hickman RK, Curiale MS, Hillen W, Levy SB. Constitutive expression of tetracycline resistance mediated by a Tn10-like element in Haemophilus parainfluenzae results from a mutation in the repressor gene. J Bacteriol 1987; 169: 990-4.
42. Hoflack G, Maes D, Mateusen B, Verdonck M, de Kruif A. Efficacy of tilmicosin phosphate (Pulmotil premix) in feed for the treatment of a clinical outbreak of Actinobacillus pleuropneumoniae infection in growing-finishing pigs. J Vet Med B Infect Dis Vet Public Health 2001; 48: 655-64.
43. Hoppe JE, Haug A. Antimicrobial susceptibility of Bordetella pertussis (Part I). Infection 1988; 16: 126-30.
44. Hörmansdorfer S, Bauer J. [Resistance of bovine and porcine Pasteurella to florfenicol and other antibiotics]. Berl Münch Tierärztl Wochenschr 1998; 111: 422-6.
45. Hotomi M, Fujihara K, Sakai A, Billal DS, Shimada J, Suzumoto M, Yamanaka N. Antimicrobial resistance of Haemophilus influenzae isolated from the nasopharynx of Japanese children with acute otitis media. Acta Otolaryngol 2006; 126: 240-7.
46. Hunt ML, Adler B, Townsend KM. The molecular biology of Pasteurella multocida. Vet Microbiol 2000;
72: 3-25.
47. Ito H, Ishii H, Akiba M. Analysis of the complete nucleotide sequence of an Actinobacillus pleuropneumoniae streptomycin-sulfonamide resistance plasmid, pMS260. Plasmid 2004; 51: 41-7.
48. Jackwood MW, Saif YM, Coplin DL. Isolation and characterization of Bordetella avium plasmids. Avian Dis 1987; 31: 782-6.
49. Katzenstein DA, Ciofalo L, Jordan MC. Bordetella bronchiseptica bacteremia. West J Med 1984; 140: 96-8.
50. Kehrenberg C, Meunier D, Targant H, Cloeckaert A, Schwarz S, Madec JY. Plasmid-mediated florfenicol resistance in Pasteurella trehalosi. J Antimicrob Chemother 2006; 58: 13-7.
51. Kehrenberg C, Schwarz S. Distribution of florfenicol resistance genes fexA and cfr among chloramphenicol-resistant Staphylococcus isolates. Antimicrob Agents Chemother 2006; 50: 1156-63.
52. Kehrenberg C, Schwarz S. Plasmid-borne florfenicol resistance in Pasteurella multocida. J Antimicrob Chemother 2005; 55: 773-5.
53. Kehrenberg C, Schwarz S. dfrA20, A novel trimethoprim resistance gene from Pasteurella multocida.
Antimicrob Agents Chemother 2005; 49: 414-7.
54. Kehrenberg C, Schwarz S, Jacobsen L, Hansen LH, Vester B. A new mechanism for chloramphenicol, florfenicol and clindamycin resistance: methylation of 23S ribosomal RNA at A2503. Mol Microbiol 2005;
57: 1064-73.
55. Kehrenberg C, Mumme J, Wallmann J, Verspohl J, Tegeler R, Kühn T, Schwarz S. Monitoring of florfenicol susceptibility among bovine and porcine respiratory tract pathogens collected in Germany during the years 2002 and 2003. J Antimicrob Chemother 2004; 54: 572-4.
General discussion chapter 7
56. Kehrenberg C, Schwarz S. fexA, a novel Staphylococcus lentus gene encoding resistance to florfenicol and chloramphenicol. Antimicrob Agents Chemother 2004; 48: 615-8.
57. Kehrenberg C, Salmon SA, Watts JL, Schwarz S. Tetracycline resistance genes in isolates of Pasteurella multocida, Mannheimia haemolytica, Mannheimia glucosida and Mannheimia varigena from bovine and swine respiratory disease: intergeneric spread of the tet(H) plasmid pMHT1. J Antimicrob Chemother 2001;
48: 631-40.
58. Kehrenberg C, Schulze-Tanzil G, Martel JL, Chaslus-Dancla E, Schwarz S. Antimicrobial resistance in Pasteurella and Mannheimia: epidemiology and genetic basis. Vet Res 2001; 32: 323-39.
59. Kehrenberg C, Schwarz S. Molecular analysis of tetracycline resistance in Pasteurella aerogenes.
Antimicrob Agents Chemother 2001; 45: 2885-90.
60. Köfer J, Hinterdorfer F, Awad-Masalmeh M. [Occurrence and drug resistance of bacteria pathogenic to the lungs from autopsy material of swine]. Tierärztl Prax 1992; 20: 600-4.
61. Kubota T, Higa F, Kusano N, Nakasone I, Haranage S, Tateyama M, Yamane N, Fujita J. Genetic analyses of beta-lactamase negative ampicillin-resistant strains of Haemophilus influenzae isolated in Okinawa, Japan. Jpn J Infect Dis 2006 ; 59: 36-41.
62. Lancashire JF, Terry TD, Blackall PJ, Jennings MP. Plasmid-encoded Tet B tetracycline resistance in Haemophilus parasuis. Antimicrob Agents Chemother 2005; 49: 1927-31.
63. Lartigue MF, Poirel L, Fortineau N, Nordmann P. Chromosome-borne class A BOR-1 beta-Lactamase of Bordetella bronchiseptica and Bordetella parapertussis. Antimicrob Agents Chemother 2005; 49: 2565-7.
64. Lax AJ, Walker CA. Plasmids related to RSF1010 from Bordetella bronchiseptica. Plasmid 1986; 15: 210-6.
65. Levy SB, Buu-Hoi A, Marshall B. Transposon Tn10-like tetracycline resistance determinants in Haemophilus parainfluenzae. J Bacteriol 1984; 160: 87-94.
66. Li XZ, Nikaido H. Efflux-mediated drug resistance in bacteria. Drugs 2004; 64: 159-204.
67. Markowska-Daniel I, Pejsak Z. Efficacy of a combination of amoxicillin and clavulanic acid in the treatment of pneumonia of pigs. Dtsch Tierärztl Wochenschr 1999; 106: 518-22.
68. Maynard C, Fairbrother JM, Bekal S, Sanschagrin F, Levesque RC, Brousseau R, Masson L, Lariviere S, Harel J. Antimicrobial resistance genes in enterotoxigenic Escherichia coli O149:K91 isolates obtained over a 23-year period from pigs. Antimicrob Agents Chemother 2003; 47: 3214-21.
69. Mengelers MJ, van Klingeren B, van Miert AS. In vitro susceptibility of some porcine respiratory tract pathogens to aditoprim, trimethoprim, sulfadimethoxine, sulfamethoxazole, and combinations of these agents. Am J Vet Res 1990; 51: 1860-4.
70. Miko A, Pries K, Schroeter A, Helmuth R. Multiple-drug resistance in D-tartrate-positive Salmonella enterica serovar Paratyphi B isolates from poultry is mediated by class 2 integrons inserted into the bacterial chromosome. Antimicrob Agents Chemother 2003; 47: 3640-3.
71. Nikaido H. Role of permeability barriers in resistance to beta-lactam antibiotics. Pharmacol Ther 1985; 27:
197-231.
72. Ojo KK, Kehrenberg C, Odelola HA, Schwarz S. Structural analysis of the tetracycline resistance gene region of a small multiresistance plasmid from uropathogenic Escherichia coli isolated in Nigeria. J Antimicrob Chemother 2003; 52: 1043-4.
73. Paulsen IT, Brown MH, Skurray RA. Proton-dependent multidrug efflux systems. Microbiol Rev 1996; 60:
575-608.
74. Perreten V, Boerlin P. A new sulfonamide resistance gene (sul3) in Escherichia coli is widespread in the pig population of Switzerland. Antimicrob Agents Chemother 2003; 47: 1169-72.
75. Petersen A, Guardabassi L, Dalsgaard A, Olsen JE. Class I integrons containing a dhfrI trimethoprim resistance gene cassette in aquatic Acinetobacter spp. FEMS Microbiol Lett 2000; 182: 73-6.
76. Pijpers A, Van Klingeren B, Schoevers EJ, Verheijden JH, Van Miert AS. In vitro activity of five tetracyclines and some other antimicrobial agents against four porcine respiratory tract pathogens. J Vet Pharmacol Ther 1989; 12: 267-76.
77. Poole K. Resistance to β-lactam antibiotics. Cell Mol Life Sci 2004; 61: 2200-23.
78. Post KW, Cole NA, Raleigh RH. In vitro antimicrobial susceptibility of Pasteurella haemolytica and Pasteurella multocida recovered from cattle with bovine respiratory disease complex. J Vet Diagn Invest 1991; 3: 124-6.
79. Priebe S, Schwarz S. In vitro activities of florfenicol against bovine and porcine respiratory tract pathogens.
Antimicrob Agents Chemother 2003; 47: 2703-5.
80. Raemdonck DL, Tanner AC, Tolling ST, Michener SL. Antimicrobial susceptibility of Actinobacillus pleuropneumoniae, Pasteurella multocida and Salmonella choleraesuis isolates from pigs. Vet Rec 1994;
134: 5-7.
81. Ramirez MS, Quiroga C, Centron D. Novel rearrangement of a class 2 integron in two non-epidemiologically related isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 2005; 49:
5179-81.
82. Roe MT, Vega E, Pillai SD. Antimicrobial resistance markers of class 1 and class 2 integron-bearing Escherichia coli from irrigation water and sediments. Emerg Infect Dis 2003; 9: 822-6.
83. Rosser SJ, Young HK. Identification and characterization of class 1 integrons in bacteria from an aquatic environment. J Antimicrob Chemother 1999; 44: 11-8.
84. Salmon SA, Watts JL, Case CA, Hoffman LJ, Wegener HC, Yancey RJ, Jr. Comparison of MICs of ceftiofur and other antimicrobial agents against bacterial pathogens of swine from the United States, Canada, and Denmark. J Clin Microbiol 1999; 533: 2435-44.
85. Sanchez L, Pan W, Vinas M, Nikaido H. The acrAB homolog of Haemophilus influenzae codes for a functional multidrug efflux pump. J Bacteriol 1997; 179: 6855-7.
86. Sandvang D. Novel streptomycin and spectinomycin resistance gene as a gene cassette within a class 1 integron isolated from Escherichia coli. Antimicrob Agents Chemother 1999; 43: 3036-8.
87. Schwarz S. 2006. personal communication.
88. Schwarz S, Kehrenberg C, Doublet B, Cloeckaert A. Molecular basis of bacterial resistance to chloramphenicol and florfenicol. FEMS Microbiol Rev 2004; 28: 519-42.
89. Schwarz S, Böttner A, Hafez HM, Kehrenberg C, Kietzmann M, Klarmann D, Klein G, Krabisch P, Kühn T, Luhofer G, Richter A, Traeder W, Waldmann KH, Wallmann J, Werckenthin C. [Antimicrobial susceptibility testing of bacteria isolated from animals: methods for in-vitro susceptibility testing and their suitability with regard to the generation of the most useful data for therapeutic applications]. Berl Münch Tierärztl Wochenschr 2003; 116: 353-61.
90. Shimizu M, Kuninori K, Inoue M, Mitsuhashi S. Drug resistance and R plasmids in Bordetella bronchiseptica isolates from pigs. Microbiol Immunol 1981; 25: 773-86.
91. Shimoni Z, Niven M, Mosenkis M, Greif J. Fatal pneumonia due to Bordetella bronchiseptica. Isr Med Assoc J 2000; 2: 402-3.
92. Shin SJ, Kang SG, Nabin R, Kang ML, Yoo HS. Evaluation of the antimicrobial activity of florfenicol against bacteria isolated from bovine and porcine respiratory disease. Vet Microbiol 2005; 106: 73-7.
93. Shryock TR, Staples JM, DeRosa DC. Minimum inhibitory concentration breakpoints and disk diffusion inhibitory zone interpretive criteria for tilmicosin susceptibility testing against Pasteurella multocida and Actinobacillus pleuropneumoniae associated with porcine respiratory disease. J Vet Diagn Invest 2002; 14:
389-95.
94. Speakman AJ, Dawson S, Corkill JE, Binns SH, Hart CA, Gaskell RM. Antibiotic susceptibility of canine Bordetella bronchiseptica isolates. Vet Microbiol 2000; 71: 193-200.
General discussion chapter 7
95. Speakman AJ, Binns SH, Osborn AM, Corkill JE, Kariuki S, Saunders JR, Dawson S, Gaskell RM, Hart CA. Characterization of antibiotic resistance plasmids from Bordetella bronchiseptica. J Antimicrob Chemother 1997; 40: 811-6.
96. Stokes HW, O'Gorman DB, Recchia GD, Parsekhian M, Hall RM. Structure and function of 59-base element recombination sites associated with mobile gene cassettes. Mol Microbiol 1997; 26: 731-45.
97. Sulavik MC, Houseweart C, Cramer C, Jiwani N, Murgolo N, Greene J, DiDomenico B, Shaw KJ, Miller GH, Hare R, Shimer G. Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes. Antimicrob Agents Chemother 2001; 45: 1126-36.
98. Sunde M. Prevalence and characterization of class 1 and class 2 integrons in Escherichia coli isolated from meat and meat products of Norwegian origin. J Antimicrob Chemother 2005; 56: 1019-24.
99. Sunde M, Sørum H. Self-transmissible multidrug resistance plasmids in Escherichia coli of the normal intestinal flora of healthy swine. Microb Drug Resist 2001; 7: 191-6.
100. Sunde M, Sørum H. Characterization of integrons in Escherichia coli of the normal intestinal flora of swine. Microb Drug Resist 1999; 5: 279-87.
101. Tennstedt T, Szczepanowski R, Braun S, Pühler A, Schlüter A. Occurrence of integron-associated resistance gene cassettes located on antibiotic resistance plasmids isolated from a wastewater treatment plant. FEMS Microbiol Ecol 2003; 45: 239-52.
102. Terakado N, Araki S, Mori Y, Sekizaki T, Hashimoto K. Non-conjugative R plasmid with five drug resistance from Bordetella bronchiseptica of pig origin. Nippon Juigaku Zasshi 1981; 43: 971-4.
103. Terakado N, Mitsuhashi S. Properties of R factors from Bordetella bronchiseptica. Antimicrob Agents Chemother 1974; 6: 836-40.
104. Terakado N, Azechi H, Ninomiya K, Shimizu T. Demonstration of R factors in Bordetella bronchiseptica isolated from pigs. Antimicrob Agents Chemother 1973; 3: 555-8.
105. Tortola MT, Lavilla S, Miro E, Gonzalez JJ, Larrosa N, Sabate M, Navarro F, Prats G. First detection of a carbapenem-hydrolyzing metalloenzyme in two Enterobacteriaceae isolates in Spain. Antimicrob Agents Chemother 2005; 49: 3492-4.
106. Tosini F, Visca P, Luzzi I, Dionisi AM, Pezzella C, Petrucca A, Carattoli A. Class 1 integron-borne multiple-antibiotic resistance carried by IncFI and IncL/M plasmids in Salmonella enterica serotype Typhimurium. Antimicrob Agents Chemother 1998; 42: 3053-8.
107. Tozzi AE, Celentano LP, Ciofi degli Atti ML, Salmaso S. Diagnosis and management of pertussis. CMAJ 2005; 172: 509-15.
108. Vester B, Douthwaite S. Macrolide resistance conferred by base substitutions in 23S rRNA. Antimicrob Agents Chemother 2001; 45: 1-12.
109. Wallmann J, Kaspar H, Kroker R. [The prevalence of antimicrobial susceptibility of veterinary pathogens isolated from cattle and pigs: national antibiotic resistance monitoring 2002/2003 of the BVL]. Berl Münch Tierärztl Wochenschr 2004; 117: 480-92.
110. Waters SH, Rogowsky P, Grinsted J, Altenbuchner J, Schmitt R. The tetracycline resistance determinants of RP1 and Tn1721: nucleotide sequence analysis. Nucleic Acids Res 1983; 11: 6089-105.
111. Waturangi DE, Schwarz S, Suwanto A, Kehrenberg C, Erdelen W. Identification of a truncated Tn1721-like transposon located on a small plasmid of Escherichia coli isolated from Varanus indicus. J Vet Med B Infect Dis Vet Public Health 2003; 50: 86-9.
112. Wettstein K, Frey J. [Comparison of antimicrobial resistance pattern of selected respiratory tract pathogens isolated from different animal species]. Schweiz Arch Tierheilkd 2004; 146: 417-22.
113. Wettstein K. Vergleich der antimikrobiellen Reistenz von ausgewählten Infektionserregern des Respirationstraktes bei verschiedenen Tierarten. Veterinär-Bakteriologie. Universität Bern: Bern. 2000; 66.
114. White PA, McIver CJ, Rawlinson WD. Integrons and gene cassettes in the Enterobacteriaceae. Antimicrob Agents Chemother 2001; 45: 2658-61.
115. Wiegand I. Molekulare und biochemische Grundlagen der Beta-Lactam-Resistenz durch Beta-Lactamasen.
Chemother J 2003; 12: 151-64.
116. Wissing A, Nicolet J, Boerlin P. [The current antimicrobial resistance situation in Swiss veterinary medicine]. Schweiz Arch Tierheilkd 2001; 143: 503-10.
117. Wu JR, Shieh HK, Shien JH, Gong SR, Chang PC. Molecular characterization of plasmids with antimicrobial resistant genes in avian isolates of Pasteurella multocida. Avian Dis 2003; 47: 1384-92.
118. Yaginuma S, Terakado N, Mitsuhashi S. Biochemical properties of a penicillin beta-lactamase mediated by R factor from Bordetella bronchiseptica. Antimicrob Agents Chemother 1975; 8: 238-42.
119. Yoshimura H, Ishimaru M, Endoh YS, Kojima A. Antimicrobial susceptibility of Pasteurella multocida isolated from cattle and pigs. J Vet Med B Infect Dis Vet Public Health 2001; 48: 555-60.
Summary chapter 8
Chapter 8
Summary
Summary chapter 8
Kristina Kadlec: Detection and Organization of antimicrobial resistance genes in Bordetella bronchiseptica isolates from pigs
Bordetella bronchiseptica is a Gram-negative respiratory tract pathogen. In pigs, it causes various symptoms ranging from mild rhinitis to severe pneumonia. Moreover, B.
bronchiseptica infections predispose pigs to infections with other pathogens, e.g. toxigenic Pasteurella multocida. Antimicrobial agents are frequently used to control respiratory tract infections in swine production. In contrast to other well-studied respiratory tact pathogens, little is known about antimicrobial resistance and resistance genes in B. bronchiseptica. The aims of this study were to 1) provide an overview on antimicrobial resistance of German B.
bronchiseptica isolates from pigs, 2) detect genes that confer resistance to selected antimicrobial agents in B. bronchiseptica, and 3) identify their localization on mobile genetic elements and their transferability.
In the first part of the study 349 B. bronchiseptica isolates, which had been collected from pigs with respiratory tract disease between 2000 and 2003, were investigated for their susceptibility to 15 antimicrobial agents or combinations of agents by microdilution according to CLSI recommendations [chapter 2]. Interpretation of these results was hampered by the lack of breakpoints for a classification of the minimum inhibitory concentrations (MICs) into one of the three categories “susceptible”, “intermediate” or “resistant”. Such approved B.
bronchiseptica-specific breakpoints are currently available only for a single antimicrobial agent, namely florfenicol. For florfenicol, 2.9% of the isolates were resistant and 17.5% were classified as intermediately susceptible. The B. bronchiseptica isolates differed in their antimicrobial susceptibility from other porcine respiratory tract pathogens, such as Pasteurella multocida or Actinobacillus pleuropneumoniae.
For the following parts of the study, isolates were chosen for further investigations on the basis of their MICs [chapters 3-6]. Six isolates showed high MICs to trimethoprim and genes coding for trimethoprim-resistant dihydrofolate reductases (dfr genes) were identified
For the following parts of the study, isolates were chosen for further investigations on the basis of their MICs [chapters 3-6]. Six isolates showed high MICs to trimethoprim and genes coding for trimethoprim-resistant dihydrofolate reductases (dfr genes) were identified