RamA, a member of the AraC/XylS family, influences both virulence and efflux in Salmonella enterica serovar typhimurium

Journal of Bacteriology

Volumn 192, Issue 6, 2010, Pages 1607-1616

  Bailey, Andrew M ^a   Ivens, Al ^b   Kingsley, Rob ^a,c   Cottell, Jennifer L ^a   Wain, John ^b,d   Piddock, Laura J V ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^c Fios Genomics Ltd   (United Kingdom)

^d PUBLIC HEALTH ENGLAND   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSCRIPTOME;

ACRAB GENE; ACREF GENE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BACTERIAL GENE; BACTERIAL SURVIVAL; BACTERIAL VIRULENCE; CAENORHABDITIS ELEGANS; CONSENSUS SEQUENCE; CONTROLLED STUDY; FEMALE; GENE INACTIVATION; GENE OVEREXPRESSION; ILVM GENE; MACROPHAGE; MOUSE; MULTIDRUG RESISTANCE; NONHUMAN; PATHOGENICITY ISLAND; PCKA GENE; PLASMID; PRIORITY JOURNAL; PROMOTER REGION; RAMA GENE; RAMR GENE; REGULON; SALMONELLA TYPHIMURIUM; SIPABC GENE; SSRA GENE; TOLC GENE; TRANSCRIPTION INITIATION;

ANIMALS; BACTERIAL PROTEINS; CAENORHABDITIS ELEGANS; CARRIER PROTEINS; CELL LINE; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, BACTERIAL; MACROPHAGES; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PORINS; SALMONELLA INFECTIONS; SALMONELLA TYPHIMURIUM; TRANS-ACTIVATORS; VIRULENCE;

CAENORHABDITIS ELEGANS; SALMONELLA; SALMONELLA ENTERICA SUBSP. ENTERICA SEROVAR TYPHIMURIUM;

EID: 77949383631     PISSN: 00219193     EISSN: None     Source Type: Journal    
DOI: 10.1128/JB.01517-09     Document Type: Article

References (73)

1. Aballay, A., and F. M. Ausubel. 2001. Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella typhimurium-mediated killing. Proc. Natl. Acad. Sci. U. S. A. 98:2735-2739.
2. Aballay, A., P. Yorgey, and F. M. Ausubel. 2000. Salmonella typhimurium proliferates and establishes a persistent infection in the intestine of Caenorhabditis elegans. Curr. Biol. 10:1539-1542.
3. Abouzeed, Y. M., S. Baucheron, and A. Cloeckaert. 2008. ramR mutations involved in efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium. Antimicrob. Agents Chemother. 52:2428-2434.
4. Aono, R., N. Tsukagoshi, and M. Yamamoto. 1998. Involvement of outer membrane protein TolC, a possible member of the mar-sox regulon, in maintenance and improvement of organic solvent tolerance of Escherichia coli K-12. J. Bacteriol. 180:938-944.
5. Ariza, R. R., Z. Li, N. Ringstad, and B. Demple. 1995. Activation of multiple antibiotic resistance and binding of stress-inducible promoters by Escherichia coli Rob protein. J. Bacteriol. 177:1655-1661.
6. Bailey, A. M., I. T. Paulsen, and L. J. Piddock. 2008. RamA confers multidrug resistance in Salmonella enterica via increased expression of acrB, which is inhibited by chlorpromazine. Antimicrob. Agents Chemother. 52:3604-3611.
7. Bailey, A. M., M. A. Webber, and L. J. Piddock. 2006. Medium plays a role in determining expression of acrB, marA, and soxS in Escherichia coli. Antimicrob. Agents Chemother. 50:1071-1074.
8. Barbosa, T. M., and S. B. Levy. 2000. Differential expression of over 60 chromosomal genes in Escherichia coli by constitutive expression of MarA. J. Bacteriol. 182:3467-3474.
9. Baucheron, S., H. Imberechts, E. Chaslus-Dancla, and A. Cloeckaert. 2002. The AcrB multidrug transporter plays a major role in high-level fluoroquinolone resistance in Salmonella enterica serovar typhimurium phage type DT204. Microb. Drug Resist. 8:281-289.
10. Baucheron, S., C. Mouline, K. Praud, E. Chaslus-Dancla, and A. Cloeckaert. 2005. TolC but not AcrB is essential for multidrug-resistant Salmonella enterica serotype Typhimurium colonization of chicks. J. Antimicrob. Chemother. 55:707-712.
11. Bina, X. R., C. L. Lavine, M. A. Miller, and J. E. Bina. 2008. The AcrAB RND efflux system from the live vaccine strain of Francisella tularensis is a multiple drug efflux system that is required for virulence in mice. FEMS Microbiol. Lett. 279:226-233.
12. Bowden, S. D., G. Rowley, J. C. Hinton, and A. Thompson. 2009. Glucose and glycolysis are required for the successful infection of macrophages and mice by Salmonella enterica serovar Typhimurium. Infect. Immun. 77:3117-3126.
13. Brenner, S. 1974. The genetics of Caenorhabditis elegans. Genetics 77: 71-94.
14. Buckley, A. M., M. A. Webber, S. Cooles, L. P. Randall, R. M. La Ragione, M. J. Woodward, and L. J. Piddock. 2006. The AcrAB-TolC efflux system of Salmonella enterica serovar Typhimurium plays a role in pathogenesis. Cell Microbiol. 8:847-856.
15. Bunikis, I., K. Denker, Y. Ostberg, C. Andersen, R. Benz, and S. Bergstrom. 2008. An RND-type efflux system in Borrelia burgdorferi is involved in virulence and resistance to antimicrobial compounds. PLoS Pathog. 4:e1000009.
16. Burse, A., H. Weingart, and M. S. Ullrich. 2004. The phytoalexin-inducible multidrug efflux pump AcrAB contributes to virulence in the fire blight pathogen, Erwinia amylovora. Mol. Plant Microbe. Interact. 17:43-54.
17. Chaudhuri, R. R., N. J. Loman, L. A. S. Snyder, C. M. Bailey, D. J. Stekel, and M. J. Pallen. 2008. xBASE2: a comprehensive resource for comparative bacterial genomics. Nucleic Acids Res. 36:D543-546.
18. Chaudhuri, R. R., S. E. Peters, S. J. Pleasance, H. Northen, C. Willers, G. K. Paterson, D. B. Cone, A. G. Allen, P. J. Owen, G. Shalom, D. J. Stekel, I. G. Charles, and D. J. Maskell. 2009. Comprehensive identification of Salmonella enterica serovar Typhimurium genes required for infection of BALB/c mice. PLoS Pathog. 5:e1000529.
19. Chollet, R., J. Chevalier, C. Bollet, J. M. Pages, and A. Davin-Regli. 2004. RamA is an alternate activator of the multidrug resistance cascade in Enterobacter aerogenes. Antimicrob. Agents Chemother. 48:2518-2523.
20. Cohen, S. P., H. Hachler, and S. B. Levy. 1993. Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli. J. Bacteriol. 175:1484-1492.
21. Cohen, S. P., L. M. McMurry, and S. B. Levy. 1988. marA locus causes decreased expression of OmpF porin in multiple-antibiotic-resistant (Mar) mutants of Escherichia coli. J. Bacteriol. 170:5416-5422.
22. Datsenko, K. A., and B. L. Wanner. 2000. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc. Natl. Acad. Sci. U. S. A. 97:6640-6645.
23. Demple, B., and C. F. Amábile-Cuevas. 1991. Redox redux: The control of oxidative stress responses. Cell 67:837-839.
24. Eaves, D. J., V. Ricci, and L. J. V. Piddock. 2004. Expression of acrB, acrF, acrD, marA, and soxS in Salmonella enterica serovar Typhimurium: role in multiple antibiotic resistance. Antimicrob. Agents Chemother. 48:1145-1150.
25. Eriksson, S., S. Lucchini, A. Thompson, M. Rhen, and J. C. Hinton. 2003. Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica. Mol. Microbiol. 47:103-118.
26. Fass, E., and E. A. Groisman. 2009. Control of Salmonella pathogenicity island-2 gene expression. Curr. Opin. Microbiol. 12:199-204.
27. Fralick, J. A. 1996. Evidence that TolC is required for functioning of the Mar/AcrAB efflux pump of Escherichia coli. J. Bacteriol. 178:5803-5805.
28. George, A. M., R. M. Hall, and H. W. Stokes. 1995. Multidrug resistance in Klebsiella pneumoniae: a novel gene, ramA, confers a multidrug resistance phenotype in Escherichia coli. Microbiology 141(Pt. 8):1909-1920.
29. Giraud, E., A. Cloeckaert, D. Kerboeuf, and E. Chaslus-Dancla. 2000. Evidence for active efflux as the primary mechanism of resistance to ciprofloxacin in Salmonella enterica serovar Typhimurium. Antimicrob. Agents Chemother. 44:1223-1228.
30. Griffith, K. L., and R. E. Wolf, Jr. 2001. Systematic mutagenesis of the DNA binding sites for SoxS in the Escherichia coli zwf and fpr promoters: identifying nucleotides required for DNA binding and transcription activation. Mol. Microbiol. 40:1141-1154.
31. Hachler, H., S. P. Cohen, and S. B. Levy. 1991. marA, a regulated locus which controls expression of chromosomal multiple antibiotic resistance in Escherichia coli. J. Bacteriol. 173:5532-5538.
32. Hernandez-Urzua, E., D. S. Zamorano-Sanchez, J. Ponce-Coria, E. Morett, S. Grogan, R. K. Poole, and J. Membrillo-Hernandez. 2007. Multiple regulators of the flavohaemoglobin (hmp) gene of Salmonella enterica serovar Typhimurium include RamA, a transcriptional regulator conferring the multidrug resistance phenotype. Arch. Microbiol. 187:67-77.
33. Hope, I. A. (ed.). 1999. C. elegans: a practical approach. Oxford University Press, Oxford, United Kingdom.
34. Hulbert, R. R., and R. K. Taylor. 2002. Mechanism of ToxT-dependent transcriptional activation at the Vibrio cholerae tcpA promoter. J. Bacteriol. 184:5533-5544.
35. Jair, K. W., X. Yu, K. Skarstad, B. Thony, N. Fujita, A. Ishihama, and R. E. Wolf, Jr. 1996. Transcriptional activation of promoters of the superoxide and multiple antibiotic resistance regulons by Rob, a binding protein of the Escherichia coli origin of chromosomal replication. J. Bacteriol. 178:2507-2513.
36. Kaniga, K., J. C. Bossio, and J. E. Galan. 1994. The Salmonella typhimurium invasion genes invF and invG encode homologues of the AraC and PulD family of proteins. Mol. Microbiol. 13:555-568.
37. Karp, P. D., S. Paley, and P. Romero. 2002. The Pathway Tools software. Bioinformatics 18:S225-232.
38. Keeney, D., A. Ruzin, and P. A. Bradford. 2007. RamA, a transcriptional regulator, and AcrAB, an RND-type efflux pump, are associated with decreased susceptibility to tigecycline in Enterobacter cloacae. Microb. Drug Resist. 13:1-6.
39. Kingsley, R. A., A. D. Humphries, E. H. Weening, M. R. de Zoete, S. Winter, A. Papaconstantinopoulou, G. Dougan, and A. J. Baumler. 2003. Molecular and phenotypic analysis of the CS54 island of Salmonella enterica serotype Typhimurium: identification of intestinal colonization and persistence determinants. Infect. Immun. 71:629-640.
40. Linehan, S. A., A. Rytkonen, X.-J. Yu, M. Liu, and D. W. Holden. 2005. SlyA regulates function of Salmonella pathogenicity island 2 (SPI-2) and expression of SPI-2-associated genes. Infect. Immun. 73:4354-4362.
41. Martin, R. G., E. S. Bartlett, J. L. Rosner, and M. E. Wall. 2008. Activation of the Escherichia coli marA/soxS/rob regulon in response to transcriptional activator concentration. J. Mol. Biol. 380:278-284.
42. Martin, R. G., W. K. Gillette, and J. L. Rosner. 2000. Promoter discrimination by the related transcriptional activators MarA and SoxS: differential regulation by differential binding. Mol. Microbiol. 35:623-634.
43. Martin, R. G., K. W. Jair, R. E. Wolf, Jr., and J. L. Rosner. 1996. Autoactivation of the marRAB multiple antibiotic resistance operon by the MarA transcriptional activator in Escherichia coli. J. Bacteriol. 178:2216-2223.
44. Martin, R. G., and J. L. Rosner. 2002. 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. 44:1611-1624.
45. McClelland, M., K. E. Sanderson, J. Spieth, S. W. Clifton, P. Latreille, L. Courtney, S. Porwollik, J. Ali, M. Dante, F. Du, S. Hou, D. Layman, S. Leonard, C. Nguyen, K. Scott, A. Holmes, N. Grewal, E. Mulvaney, E. Ryan, H. Sun, L. Florea, W. Miller, T. Stoneking, M. Nhan, R. Waterston, and R. K. Wilson. 2001. Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413:852-856.
46. McMurry, L. M., M. Oethinger, and S. B. Levy. 1998. Overexpression of marA, soxS, or acrAB produces resistance to triclosan in laboratory and clinical strains of Escherichia coli. FEMS Microbiol. Lett. 166:305-309.
47. Morgan, E., A. J. Bowen, S. C. Carnell, T. S. Wallis, and M. P. Stevens. 2007. SiiE Is Secreted by the Salmonella enterica serovar Typhimurium pathogenicity island 4-encoded secretion system and contributes to intestinal colonization in cattle. Infect. Immun. 75:1524-1533.
48. Nikaido, E., A. Yamaguchi, and K. Nishino. 2008. AcrAB multidrug efflux pump regulation in Salmonella enterica serovar Typhimurium by RamA in response to environmental signals. J. Biol. Chem. 283:24245-24253.
49. Nikaido, H., M. Basina, V. Nguyen, and E. Y. Rosenberg. 1998. Multidrug efflux pump AcrAB of Salmonella typhimurium excretes only those betalactam antibiotics containing lipophilic side chains. J. Bacteriol. 180:4686-4692.
50. Perez, J. C., D. Shin, I. Zwir, T. Latifi, T. J. Hadley, and E. A. Groisman. 2009. Evolution of a bacterial regulon controlling virulence and Mg2 homeostasis. PLoS Genet 5:e1000428.
51. Piddock, L. J., D. G. White, K. Gensberg, L. Pumbwe, and D. J. Griggs. 2000. Evidence for an efflux pump mediating multiple antibiotic resistance in Salmonella enterica serovar Typhimurium. Antimicrob. Agents Chemother. 44:3118-3121.
52. Pomposiello, P. J., M. H. J. Bennik, and B. Demple. 2001. Genome-Wide Transcriptional Profiling of the Escherichia coli Responses to Superoxide Stress and Sodium Salicylate. J. Bacteriol. 183:3890-3902.
53. Prieto, A. I., S. B. Hernandez, I. Cota, M. G. Pucciarelli, Y. Orlov, F. Ramos-Morales, F. Garcia-del Portillo, and J. Casadesus. 2009. Roles of the outer membrane protein AsmA of Salmonella enterica in control of marRAB expression and invasion of epithelial cells. J. Bacteriol. 191:3615-3622.
54. Prouty, A. M., I. E. Brodsky, S. Falkow, and J. S. Gunn. 2004. Bile-saltmediated induction of antimicrobial and bile resistance in Salmonella typhimurium. Microbiology 150:775-783.
55. Ramos, J. L., F. Rojo, L. Zhou, and K. N. Timmis. 1990. A family of positive regulators related to the Pseudomonas putida TOL plasmid XylS and the Escherichia coli AraC activators. Nucleic Acids Res. 18:2149-2152.
56. Reimers, M., and V. J. Carey. 2006. Bioconductor: an open source framework for bioinformatics and computational biology. Methods Enzymol. 411: 119-134.
57. Ricci, V., and L. J. V. Piddock. 2009. Ciprofloxacin selects for multidrug resistance in Salmonella enterica serovar Typhimurium mediated by at least two different pathways. J. Antimicrob. Chemother. 63:909-916.
58. Ricci, V., P. Tzakas, A. Buckley, N. C. Coldham, and L. J. V. Piddock. 2006. Ciprofloxacin-resistant Salmonella enterica serovar Typhimurium strains are difficult to select in the absence of AcrB and TolC. Antimicrob. Agents Chemother. 50:38-42.
59. Rice, P., I. Longden, and A. Bleasby. 2000. EMBOSS: The European Molecular Biology open software suite. Trends Genet. 16:276-277.
60. Schneiders, T., S. G. B. Amyes, and S. B. Levy. 2003. Role of AcrR and RamA in fluoroquinolone resistance in clinical Klebsiella pneumoniae isolates from Singapore. Antimicrob. Agents Chemother. 47:2831-2837.
61. Stiernagle, T. 1999. Maintenance of C. elegans, p. 53-55. In I. A. Hope (ed.), C. elegans: a practical approach. Oxford University Press, Oxford, United Kingdom.
62. Sulavik, M. C., L. F. Gambino, and P. F. Miller. 1995. The MarR repressor of the multiple antibiotic resistance (mar) operon in Escherichia coli: prototypic member of a family of bacterial regulatory proteins involved in sensing phenolic compounds. Mol. Med. 1:436-446.
63. Tenor, J. L., B. A. McCormick, F. M. Ausubel, and A. Aballay. 2004. Caenorhabditis elegans-based screen identifies Salmonella virulence factors required for conserved host-pathogen interactions. Curr. Biol. 14:1018-1024.
64. Thanassi, D. G., L. W. Cheng, and H. Nikaido. 1997. Active efflux of bile salts by Escherichia coli. J. Bacteriol. 179:2512-2518.
65. Tibbetts, R. J., T. L. Lin, and C. C. Wu. 2003. Phenotypic evidence for inducible multiple antimicrobial resistance in Salmonella choleraesuis. FEMS Microbiol. Lett. 218:333-338.
66. Tobin, J. F., and R. F. Schleif. 1987. Positive regulation of the Escherichia coli L-rhamnose operon is mediated by the products of tandemly repeated regulatory genes. J. Mol. Biol. 196:789-799.
67. van der Straaten, T., R. Janssen, D. J. Mevius, and J. T. van Dissel. 2004. Salmonella gene rma (ramA) and multiple-drug-resistant Salmonella enterica serovar typhimurium. Antimicrob. Agents Chemother. 48:2292-2294.
68. Warner, D., J. Folster, W. Shafer, and A. Jerse. 2007. Regulation of the MtrC-MtrD-MtrE efflux pump system modulates the in vivo fitness of Neisseria gonorrhoeae. J. Infect. Dis. 196:1804-1812.
69. Warner, D. M., W. M. Shafer, and A. E. Jerse. 2008. Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrDMtrE efflux pump system confer different levels of antimicrobial resistance and in vivo fitness. Mol. Microbiol. 70:462-478.
70. Webber, M. A., A. M. Bailey, J. M. A. Blair, E. Morgan, M. P. Stevens, J. C. D. Hinton, A. Ivens, J. Wain, and L. J. V. Piddock. 2009. 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. 191:4276-4285.
71. White, D. G., J. D. Goldman, B. Demple, and S. B. Levy. 1997. Role of the acrAB locus in organic solvent tolerance mediated by expression of marA, soxS, or robA in Escherichia coli. J. Bacteriol. 179:6122-6126.
72. Wray, C., and W. J. Sojka. 1978. Experimental Salmonella typhimurium infection in calves. Res. Vet. Sci. 25:139-143.
73. Zheng, J., S. Cui, and J. Meng. 2009. Effect of transcriptional activators RamA and SoxS on expression of multidrug efflux pumps AcrAB and AcrEF in fluoroquinolone-resistant Salmonella Typhimurium. J. Antimicrob. Chemother. 63:95-102.