Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/66462
標題: 不同沙門氏菌血清型之ramR及ramA突變株抗藥性流行病學研究
Epidemiology of Antimicrobial Resistance in Various Salmonella Serovars with ramR/ramA Mutation
作者: 余上昱
Yu, Shan-Yu
關鍵字: 沙門氏菌;Salmonella;幫浦;藥物抗藥性;ramR 基因;ramA 基因;efflux pump;Antimicrobial Resistance;ramR gene;ramA gene
出版社: 微生物暨公共衛生學研究所
引用: 1. Tauxe RV: Emerging foodborne diseases: an evolving public health challenge. Emerg Infect Dis 1997, 3(4):425-434. 2. Mead PS, Slutsker L, Dietz V, McCaig LF, Bresee JS, Shapiro C, Griffin PM, Tauxe RV: Food-related illness and death in the United States. Emerg Infect Dis 1999, 5(5):607-625. 3. Alley MR, Connolly JH, Fenwick SG, Mackereth GF, Leyland MJ, Rogers LE, Haycock M, Nicol C, Reed CE: An epidemic of salmonellosis caused by Salmonella Typhimurium DT160 in wild birds and humans in New Zealand. N Z Vet J 2002, 50(5):170-176. 4. Renter DG, Gnad DP, Sargeant JM, Hygnstrom SE: Prevalence and serovars of Salmonella in the feces of free-ranging white-tailed deer (Odocoileus virginianus) in Nebraska. J Wildl Dis 2006, 42(3):699-703. 5. Chang CH, Chen YS, Chiou MT, Su CH, Chen DS, Tsai CE, Yu B, Hsu YM: Application of Scutellariae radix, Gardeniae fructus, and Probiotics to Prevent Salmonella enterica Serovar Choleraesuis Infection in Swine. Evid Based Complement Alternat Med 2013, 2013:568528. 6. Gorski L, Jay-Russell MT, Liang AS, Walker S, Bengson Y, Govoni J, Mandrell RE: Diversity of Pulsed-Field Gel Electrophoresis Pulsotypes, Serovars, and Antibiotic Resistance Among Salmonella Isolates from Wild Amphibians and Reptiles in the California Central Coast. Foodborne Pathog Dis 2013, 10(6):540-548. 7. Hakanen A, Siitonen A, Kotilainen P, Huovinen P: Increasing fluoroquinolone resistance in Salmonella serotypes in Finland during 1995-1997. J Antimicrob Chemother 1999, 43(1):145-148. 8. Guard-Petter J: The chicken, the egg and Salmonella Enteritidis. Environ Microbiol 2001, 3(7):421-430. 9. Hanning IB, Nutt JD, Ricke SC: Salmonellosis outbreaks in the United States due to fresh produce: sources and potential intervention measures. Foodborne Pathog Dis 2009, 6(6):635-648. 10. Molbak K: Human health consequences of antimicrobial drug-resistant Salmonella and other foodborne pathogens. Clin Infect Dis 2005, 41(11):1613-1620. 11. Sirinavin S, Garner P: Antibiotics for treating Salmonella gut infections. Cochrane Database Syst Rev 2012, 11:CD001167. 12. Poirier E, Watier L, Espie E, Weill FX, De Valk H, Desenclos JC: Evaluation of the impact on human salmonellosis of control measures targeted to Salmonella Enteritidis and Typhimurium in poultry breeding using time-series analysis and intervention models in France. Epidemiol Infect 2008, 136(9):1217-1224. 13. Chen PL, Li CY, Hsieh TH, Chang CM, Lee HC, Lee NY, Wu CJ, Lee CC, Shih HI, Ko WC: Epidemiology, disease spectrum and economic burden of non-typhoidal Salmonella infections in Taiwan, 2006-2008. Epidemiol Infect 2012, 140(12):2256-2263. 14. Ahmed AM, Ishida Y, Shimamoto T: Molecular characterization of antimicrobial resistance in Salmonella isolated from animals in Japan. J Appl Microbiol 2009, 106(2):402-409. 15. Su LH, Chiu CH, Chu C, Ou JT: Antimicrobial resistance in nontyphoid Salmonella serotypes: a global challenge. Clin Infect Dis 2004, 39(4):546-551. 16. van den Bogaard AE, Stobberingh EE: Antibiotic usage in animals: impact on bacterial resistance and public health. Drugs 1999, 58(4):589-607. 17. Swartz MN: Human diseases caused by foodborne pathogens of animal origin. Clin Infect Dis 2002, 34 (Suppl 3):S111-122. 18. Weill FX, Guesnier F, Guibert V, Timinouni M, Demartin M, Polomack L, Grimont PA: Multidrug resistance in Salmonella enterica serotype Typhimurium from humans in France (1993 to 2003). J Clin Microbiol 2006, 44(3):700-708. 19. Molbak K, Baggesen DL, Aarestrup FM, Ebbesen JM, Engberg J, Frydendahl K, Gerner-Smidt P, Petersen AM, Wegener HC: An outbreak of multidrug-resistant, quinolone-resistant Salmonella enterica serotype Typhimurium DT104. N Engl J Med 1999, 341(19):1420-1425. 20. Threlfall EJ, Frost JA, Ward LR, Rowe B: Epidemic in cattle and humans of Salmonella Typhimurium DT 104 with chromosomally integrated multiple drug resistance. Vet Rec 1994, 134(22):577. 21. Akiyama T, Khan AA: Molecular characterization of strains of fluoroquinolone-resistant Salmonella enterica serovar Schwarzengrund carrying multidrug resistance isolated from imported foods. J Antimicrob Chemother 2012, 67(1):101-110. 22. Nikaido H: Multidrug efflux pumps of gram-negative bacteria. J Bacteriol 1996, 178(20):5853-5859. 23. Escribano I, Rodriguez JC, Cebrian L, Royo G: The importance of active efflux systems in the quinolone resistance of clinical isolates of Salmonella spp. Int J Antimicrob Agents 2004, 24(5):428-432. 24. Giraud E, Cloeckaert A, Kerboeuf D, Chaslus-Dancla E: Evidence for active efflux as the primary mechanism of resistance to ciprofloxacin in Salmonella enterica serovar Typhimurium. Antimicrob Agents Chemother 2000, 44(5):1223-1228. 25. Whitehead RN, Overton TW, Kemp CL, Webber MA: Exposure of Salmonella enterica serovar Typhimurium to high level biocide challenge can select multidrug resistant mutants in a single step. PLoS One 2011, 6(7):e22833. 26. Nikaido E, Yamaguchi A, Nishino K: AcrAB multidrug efflux pump regulation in Salmonella enterica serovar Typhimurium by RamA in response to environmental signals. J Biol Chem 2008, 283(35):24245-24253. 27. Eaves DJ, Ricci V, Piddock LJ: Expression of acrB, acrF, acrD, marA, and soxS in Salmonella enterica serovar Typhimurium: role in multiple antibiotic resistance. Antimicrob Agents Chemother 2004, 48(4):1145-1150. 28. Webber MA, Bailey AM, Blair JM, Morgan E, Stevens MP, Hinton JC, Ivens A, Wain J, Piddock LJ: The global consequence of disruption of the AcrAB-TolC efflux pump in Salmonella enterica includes reduced expression of SPI-1 and other attributes required to infect the host. J Bacteriol 2009, 191(13):4276-4285. 29. Nishino K, Latifi T, Groisman EA: Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium. Mol Microbiol 2006, 59(1):126-141. 30. Gayet S, Chollet R, Molle G, Pages JM, Chevalier J: Modification of outer membrane protein profile and evidence suggesting an active drug pump in Enterobacter aerogenes clinical strains. Antimicrob Agents Chemother 2003, 47(5):1555-1559. 31. Horiyama T, Yamaguchi A, Nishino K: TolC dependency of multidrug efflux systems in Salmonella enterica serovar Typhimurium. J Antimicrob Chemother 2010, 65(7):1372-1376. 32. Li XZ, Nikaido H: Efflux-mediated drug resistance in bacteria: an update. Drugs 2009, 69(12):1555-1623. 33. Baucheron S, Imberechts H, Chaslus-Dancla E, Cloeckaert A: The AcrB multidrug transporter plays a major role in high-level fluoroquinolone resistance in Salmonella enterica serovar Typhimurium phage type DT204. Microb Drug Resist 2002, 8(4):281-289. 34. 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(10):3729-3735. 35. Baucheron S, Chaslus-Dancla E, Cloeckaert A: Role of TolC and parC mutation in high-level fluoroquinolone resistance in Salmonella enterica serotype Typhimurium DT204. J Antimicrob Chemother 2004, 53(4):657-659. 36. Karatzas KA, Webber MA, Jorgensen F, Woodward MJ, Piddock LJ, Humphrey TJ: Prolonged treatment of Salmonella enterica serovar Typhimurium with commercial disinfectants selects for multiple antibiotic resistance, increased efflux and reduced invasiveness. J Antimicrob Chemother 2007, 60(5):947-955. 37. Yu EW, McDermott G, Zgurskaya HI, Nikaido H, Koshland DE, Jr.: Structural basis of multiple drug-binding capacity of the AcrB multidrug efflux pump. Science 2003, 300(5621):976-980. 38. Koronakis V: TolC--the bacterial exit duct for proteins and drugs. FEBS Lett 2003, 555(1):66-71. 39. Pos KM: Drug transport mechanism of the AcrB efflux pump. Biochim Biophys Acta 2009, 1794(5):782-793. 40. Nishino K, Nikaido E, Yamaguchi A: Regulation and physiological function of multidrug efflux pumps in Escherichia coli and Salmonella. Biochim Biophys Acta 2009, 1794(5):834-843. 41. Ramos JL, Martinez-Bueno M, Molina-Henares AJ, Teran W, Watanabe K, Zhang X, Gallegos MT, Brennan R, Tobes R: The TetR family of transcriptional repressors. Microbiol Mol Biol Rev 2005, 69(2):326-356. 42. Beier D, Gross R: Regulation of bacterial virulence by two-component systems. Curr Opin Microbiol 2006, 9(2):143-152. 43. Nishino K, Nikaido E, Yamaguchi A: Regulation of multidrug efflux systems involved in multidrug and metal resistance of Salmonella enterica serovar Typhimurium. J Bacteriol 2007, 189(24):9066-9075. 44. Abouzeed YM, Baucheron S, Cloeckaert A: ramR mutations involved in efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium. Antimicrob Agents Chemother 2008, 52(7):2428-2434. 45. Bailey AM, Paulsen IT, Piddock LJ: RamA confers multidrug resistance in Salmonella enterica via increased expression of acrB, which is inhibited by chlorpromazine. Antimicrob Agents Chemother 2008, 52(10):3604-3611. 46. George AM, Hall RM, Stokes HW: Multidrug resistance in Klebsiella pneumoniae: a novel gene, ramA, confers a multidrug resistance phenotype in Escherichia coli. Microbiology 1995, 141 ( Pt 8):1909-1920. 47. Zheng J, Tian F, Cui S, Song J, Zhao S, Brown EW, Meng J: Differential gene expression by RamA in ciprofloxacin-resistant Salmonella Typhimurium. PLoS One 2011, 6(7):e22161. 48. Rosenblum R, Khan E, Gonzalez G, Hasan R, Schneiders T: Genetic regulation of the ramA locus and its expression in clinical isolates of Klebsiella pneumoniae. Int J Antimicrob Agents 2011, 38(1):39-45. 49. Bailey AM, Ivens A, Kingsley R, Cottell JL, Wain J, Piddock LJ: RamA, a member of the AraC/XylS family, influences both virulence and efflux in Salmonella enterica serovar Typhimurium. J Bacteriol 2010, 192(6):1607-1616. 50. Zheng J, Cui S, Meng J: Effect of transcriptional activators RamA and SoxS on expression of multidrug efflux pumps AcrAB and AcrEF in fluoroquinolone-resistant Salmonella Typhimurium. J Antimicrob Chemother 2009, 63(1):95-102. 51. O''Regan E, Quinn T, Pages JM, McCusker M, Piddock L, Fanning S: Multiple regulatory pathways associated with high-level ciprofloxacin and multidrug resistance in Salmonella enterica serovar Enteritidis: involvement of RamA and other global regulators. Antimicrob Agents Chemother 2009, 53(3):1080-1087. 52. Baucheron S, Coste F, Canepa S, Maurel MC, Giraud E, Culard F, Castaing B, Roussel A, Cloeckaert A: Binding of the RamR repressor to wild-type and mutated promoters of the RamA gene involved in efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium. Antimicrob Agents Chemother 2012, 56(2):942-948. 53. Franca LT, Carrilho E, Kist TB: A review of DNA sequencing techniques. Q Rev Biophys 2002, 35(2):169-200. 54. Xu H, Lee HY, Ahn J: Growth and virulence properties of biofilm-forming Salmonella enterica serovar Typhimurium under different acidic conditions. Appl Environ Microbiol 2010, 76(24):7910-7917. 55. Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001, 25(4):402-408. 56. Kehrenberg C, Cloeckaert A, Klein G, Schwarz S: Decreased fluoroquinolone susceptibility in mutants of Salmonella serovars other than Typhimurium: detection of novel mutations involved in modulated expression of ramA and soxS. J Antimicrob Chemother 2009, 64(6):1175-1180. 57. Hentschke M, Christner M, Sobottka I, Aepfelbacher M, Rohde H: Combined ramR mutation and presence of a Tn1721-associated tet(A) variant in a clinical isolate of Salmonella enterica serovar Hadar resistant to tigecycline. Antimicrob Agents Chemother 2010, 54(3):1319-1322. 58. Ricci V, Busby SJ, Piddock LJ: Regulation of RamA by RamR in Salmonella enterica serovar Typhimurium: isolation of a RamR superrepressor. Antimicrob Agents Chemother 2012, 56(11):6037-6040. 59. Giraud E, Baucheron S, Virlogeux-Payant I, Nishino K, Cloeckaert A: Effects of natural mutations in the ramRA locus on invasiveness of epidemic fluoroquinolone-resistant Salmonella enterica serovar Typhimurium isolates. J Infect Dis 2013, 207(5):794-802. 60. Masi M, Pages JM: Structure, Function and Regulation of Outer Membrane Proteins Involved in Drug Transport in Enterobactericeae: the OmpF/C - TolC Case. Open Microbiol J 2013, 7:22-33. 61. Zhang A, Rosner JL, Martin RG: Transcriptional activation by MarA, SoxS and Rob of two tolC promoters using one binding site: a complex promoter configuration for tolC in Escherichia coli. Mol Microbiol 2008, 69(6):1450-1455. 62. Eguchi Y, Oshima T, Mori H, Aono R, Yamamoto K, Ishihama A, Utsumi R: Transcriptional regulation of drug efflux genes by EvgAS, a two-component system in Escherichia coli. Microbiology 2003, 149(Pt 10):2819-2828. 63. Martin RG, Rosner JL: Genomics of the marA/soxS/rob regulon of Escherichia coli: identification of directly activated promoters by application of molecular genetics and informatics to microarray data. Mol Microbiol 2002, 44(6):1611-1624. 64. Swick MC, Morgan-Linnell SK, Carlson KM, Zechiedrich L: Expression of multidrug efflux pump genes acrAB-tolC, mdfA, and norE in Escherichia coli clinical isolates as a function of fluoroquinolone and multidrug resistance. Antimicrob Agents Chemother 2011, 55(2):921-924. 65. Chu C., Chiu CH, Su LH, Chu CH: Resistance to fluroquinolones linked to gyrA and parC mutations and overexpression of acrAB efflux pump in Salmonella enterica serovar Choleraesuis. Microbial Drug Resistance 2005, 11:238-244.
摘要: 
Multi-drug resistant (MDR) Salmonella has been the major issue in animals and humans, which comprises resistance of ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, tetracycline (ACSSuT), and quinolones. The expression of AcrAB-TolC efflux pump is an important antimicrobial-resistant factor, which may be associated with MDR development of Salmonella. The expression of transcriptional activator RamA regulates the promoter strength of acrA, acrB and tolC genes and affects AcrAB-TolC expression. The ramA-deleted or -removed mutants would decrease AcrAB-TolC expression and resistant levels to multiple drugs. The ramR gene is located upstream of ramA, which is a transcriptional repressor of ramA and negatively regulates ramA expression. RamR binding site is overlapped with ramA promoter region. Mutation, insertion or deletion of ramR gene or RamR binding site could significantly increase ramA expression. In this study, a total of 463 isolates of nine Salmonella serovars are molecular typed by ramR (including ramR-A intergenic region) and ramA sequences to study the individual role of these mutants in MDR of ACSSuT and quinolone resistance. Real time two-step RT-PCR by SYBR green was applied to measure relative expression of ramA, acrA, acrB and tolC genes. Our results indicated that a total of 27 ramR genotypes and 3 ramA genotypes were found in the Salmonella isolates, and most of which were firstly reported worldwide. Only mutants with partially deleted ramR gene, with more than one amino acid change or insertion subsequently causing a premature stop codon were associated with higher ramA expression. The ramA mutants themselves were not associated with higher acrA, acrB and tolC expressions, but isolates with higher expression of ramA were significantly associated with higher acrA and acrB expressions. Comparing to non-MDR isolates, higher acrA and acrB expressions were identified in MDR isolates. Moreover, in serovars of Typhimurium, Choleraesuis, Albany and Newport, proportions of isolates with higher acrA and acrB expression were significantly higher in MDR and quinolone-resistant (QR) groups, respectively.
URI: http://hdl.handle.net/11455/66462
其他識別: U0005-2207201311031800
Appears in Collections:微生物暨公共衛生學研究所

Show full item record
 

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.