Disarming bacterial virulence through chemical inhibition of the DNA binding domain of an AraC-like transcriptional activator protein

Journal of Biological Chemistry

Volumn 288, Issue 43, 2013, Pages 31115-31126

  Yang, Ji ^a   Hocking, Dianna M ^a   Cheng, Catherine ^a   Dogovski, Con ^b   Perugini, Matthew A ^b,c   Holien, Jessica K ^d   Parker, Michael W ^c,d   Hartland, Elizabeth L ^a,e   Tauschek, Marija ^a   Robins Browne, Roy M ^a,e  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b LA TROBE UNIVERSITY   (Australia)

^c ST VINCENT'S INSTITUTE OF MEDICAL RESEARCH   (Australia)

^d UNIVERSITY OF MELBOURNE   (Australia)

^e ROYAL CHILDREN'S HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC RESISTANCE; BACTERIAL INFECTIONS; CHEMICAL OPTIMIZATIONS; COMPUTATIONAL ANALYSIS; POTENTIAL DRUG TARGETS; TRANSCRIPTIONAL ACTIVATORS; TRANSCRIPTIONAL LEVELS; TRANSCRIPTIONAL REGULATOR;

AMINO ACIDS; ANTIBIOTICS; CHEMICAL COMPOUNDS; CHEMOTHERAPY; COMPLEXATION; MAMMALS; PROTEINS; TRANSCRIPTION;

PATHOGENS;

5 [(2,5 DICHLOROBENZYL)THIO] 1,3,4 THIADIAZOL 2 AMINE; ANTIINFECTIVE AGENT; ARAC PROTEIN; MEMBRANE PROTEIN; REGA PROTEIN; REGACIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BACTERIAL COLONIZATION; BACTERIAL VIRULENCE; CITROBACTER RODENTIUM; CITROBACTER RODENTIUM INFECTION; CONTROLLED STUDY; DIMERIZATION; DNA BINDING DOMAIN; DRUG BINDING SITE; DRUG SCREENING; DRUG STRUCTURE; ENTEROBACTERIACEAE INFECTION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN DNA BINDING; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN SYNTHESIS INHIBITION; TRANSCRIPTION INITIATION;

ANTIBIOTICS; ARAC-LIKE REGULATOR; BACTERIAL INFECTION; BACTERIAL PATHOGENESIS; ENTERIC PATHOGEN; GENE REGULATION; INFECTIOUS DISEASES; SMALL MOLECULE INHIBITORS; SMALL MOLECULES; VIRULENCE GENE REGULATION;

ANIMALS; ANTI-BACTERIAL AGENTS; ARAC TRANSCRIPTION FACTOR; CITROBACTER RODENTIUM; ENTEROBACTERIACEAE INFECTIONS; GENE DELETION; GENE EXPRESSION REGULATION, BACTERIAL; HELA CELLS; HUMANS; INTESTINES; MICE; PROTEIN STRUCTURE, TERTIARY; VIRULENCE FACTORS;

EID: 84886692148     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.503912     Document Type: Article

References (62)

1. Petri, W. A., Jr., Miller, M., Binder, H. J., Levine, M. M., Dillingham, R., and Guerrant, R. L. (2008) Enteric infections, diarrhea, and their impact on function and development. J. Clin. Invest. 118, 1277-1290
2. Rasko, D. A., and Sperandio, V. (2010) Anti-virulence strategies to combat bacteria-mediated disease. Nat. Rev. Drug. Discov. 9, 117-128
3. Clatworthy, A. E., Pierson, E., and Hung, D. T. (2007) Targeting virulence. A new paradigm for antimicrobial therapy. Nat. Chem. Biol. 3, 541-548
4. Gallegos, M. T., Schleif, R., Bairoch, A., Hofmann, K., and Ramos, J. L. (1997) Arac/XylS family of transcriptional regulators. Microbiol. Mol. Biol. Rev. 61, 393-410
5. Yang, J., Tauschek, M., and Robins-Browne, R. M. (2011) Control of bacterial virulence by AraC-like regulators that respond to chemical signals. Trends Microbiol. 19, 128-135
6. Dorman, C. J. (2004) H-NS. A universal regulator for a dynamic genome. Nat. Rev. Microbiol. 2, 391-400
7. Bender, J. K., Praszkier, J., Wakefield, M. J., Holt, K., Tauschek, M., Robins-Browne, R. M., and Yang, J. (2012) Involvement of PatE, a prophageencoded AraC-like regulator, in the transcriptional activation of acid resistance pathways of enterohemorrhagic Escherichia coli strain EDL933. Appl. Environ. Microbiol. 78, 5083-5092
8. Hacker, J., and Kaper, J. B. (2000) Pathogenicity islands and the evolution of microbes. Annu. Rev. Microbiol. 54, 641-679
9. Gómez-Duarte, O. G., and Kaper, J. B. (1995) A plasmid-encoded regulatory region activates chromosomal eaeA expression in enteropathogenic Escherichia coli. Infect. Immun. 63, 1767-1776
10. Srikhanta, Y. N., Hocking, D. M., Praszkier, J., Wakefield, M. J., Robins-Browne, R. M., Yang, J., and Tauschek, M. (2013) RegR virulence regulon of rabbit-specific enteropathogenic Escherichia coli strain E22. Infect. Immun. 81, 1078-1089
11. Murphree, D., Froehlich, B., and Scott, J. R. (1997) Transcriptional control of genes encoding CS1 pili. Negative regulation by a silencer and positive regulation by Rns. J. Bacteriol. 179, 5736-5743
12. Nataro, J. P., Yikang, D., Yingkang, D., and Walker, K. (1994) AggR, a transcriptional activator of aggregative adherence fimbria I expression in enteroaggregative Escherichia coli. J. Bacteriol. 176, 4691-4699
13. Di Rita, V. J., Parsot, C., Jander, G., and Mekalanos, J. J. (1991) Regulatory cascade controls virulence in Vibrio cholerae. Proc. Natl. Acad. Sci. U. S. A. 88, 5403-5407
14. Mundy, R., MacDonald, T. T., Dougan, G., Frankel, G., and Wiles, S. (2005) Citrobacter rodentium of mice and man. Cell. Microbiol. 7, 1697-1706
15. Deng, W., Puente, J. L., Gruenheid, S., Li, Y., Vallance, B. A., Vázquez, A., Barba, J., Ibarra, J. A., O'Donnell, P., Metalnikov, P., Ashman, K., Lee, S., Goode, D., Pawson, T., and Finlay, B. B. (2004) Dissecting virulence. Systematic and functional analyses of a pathogenicity island. Proc. Natl. Acad. Sci. U. S. A. 101, 3597-3602
16. Yang, J., Tauschek, M., Hart, E., Hartland, E. L., and Robins-Browne, R. M. (2010) Virulence regulation in Citrobacter rodentium. The art of timing. Microb. Biotechnol. 3, 259-268
17. Hart, E., Yang, J., Tauschek, M., Kelly, M., Wakefield, M. J., Frankel, G., Hartland, E. L., and Robins-Browne, R. M. (2008) RegA, an AraC-like protein, is a global transcriptional regulator that controls virulence gene expression in Citrobacter rodentium. Infect. Immun. 76, 5247-5256
18. Tauschek, M., Yang, J., Hocking, D., Azzopardi, K., Tan, A., Hart, E., Praszkier, J., and Robins-Browne, R. M. (2010) Transcriptional analysis of the grlRA virulence operon from Citrobacter rodentium. J. Bacteriol. 192, 3722-3734
19. Ghaem-Maghami, M., Simmons, C. P., Daniell, S., Pizza, M., Lewis, D., Frankel, G., and Dougan, G. (2001) Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium. Infect. Immun. 69, 5597-5605
20. Marchès, O., Nougayrède, J. P., Boullier, S., Mainil, J., Charlier, G., Raymond, I., Pohl, P., Boury, M., De Rycke, J., Milon, A., and Oswald, E. (2000) Role of Tir and intimin in the virulence of rabbit enteropathogenic Escherichia coli serotype O103:H2. Infect. Immun. 68, 2171-2182
21. Evans, D. G., Evans, D. J., Jr., and Pierce, N. F. (1973) Differences in the response of rabbit small intestine to heat-labile and heat-stable enterotoxins of Escherichia coli. Infect. Immun. 7, 873-880
22. Nataro, J. P., Deng, Y., Cookson, S., Cravioto, A., Savarino, S. J., Guers, L. D., Levine, M. M., and Tacket, C. O. (1995) Heterogeneity of enteroaggregative Escherichia coli virulence demonstrated in volunteers. J. Infect. Dis. 171, 465-468
23. Salim, A., Lan, R., and Reeves, P. R. (2005) Vibrio cholerae pathogenic clones. Emerg. Infect. Dis. 11, 1758-1760
24. Casadaban, M. J. (1976) Transposition and fusion of the lac genes to selected promoters in Escherichia coli using bacteriophage λand μ. J. Mol. Biol. 104, 541-555
25. Yang, J., Ganesan, S., Sarsero, J., and Pittard, A. J. (1993) A genetic analysis of various functions of the TyrR protein of Escherichia coli. J. Bacteriol. 175, 1767-1776
26. Chang, A. C., and Cohen, S. N. (1978) Construction and characterization of amplifiable multicopy DNA cloning vehicles derived from the P15A cryptic miniplasmid. J. Bacteriol. 134, 1141-1156
27. Yang, J., Hart, E., Tauschek, M., Price, G. D., Hartland, E. L., Strugnell, R. A., and Robins-Browne, R. M. (2008) Bicarbonate-mediated transcriptional activation of divergent operons by the virulence regulatory protein, RegA, from Citrobacter rodentium. Mol. Microbiol. 68, 314-327
28. Yang, J., Murakami, K., Camakaris, H., Fujita, N., Ishihama, A., and Pittard, A. J. (1997) Amino acid residues in the α-subunit C-terminal domain of Escherichia coli RNA polymerase involved in activation of transcription from the mtr promoter. J. Bacteriol. 179, 6187-6191
29. Argaet, V. P., Wilson, T. J., and Davidson, B. E. (1994) Purification of the Escherichia coli regulatory protein TyrR and analysis of its interactions with ATP, tyrosine, phenylalanine, and tryptophan. J. Biol. Chem. 269, 5171-5178
30. Sambrook, J., and Russell, D. W. (2001) Molecular Cloning: A Laboratory Manual, 3rd Ed., pp. A2.2, Cold Spring Harbour Laboratory Press, Cold Spring Harbour, NY
31. Miller, J. H. (1974) Experiments in Molecular Genetics, Cold Spring Harbour Laboratory Press, Plainview, NY
32. Laue, T. M., Shah, B. D., Ridgeway, T. M., and Pelletier, S. L. (1992) in Analytical Ultracentrifugation in Biochemistry and Polymer Sciences (Harding, S. E., Rowe, A. J., and Horton, J. C., eds) pp. 90-125, The Royal Society of Chemistry, Cambridge, UK
33. Schuck, P. (2000) Size-distribution analysis of macromolecules by sedimentation velocity ultracentrifugation and lamm equation modeling. Biophys. J. 78, 1606-1619
34. Söding, J., Biegert, A., and Lupas, A. N. (2005) The HHpred interactive server for protein homology detection and structure prediction. Nucleic Acids Res. 33, W244-W248
35. Lowden, M. J., Skorupski, K., Pellegrini, M., Chiorazzo, M. G., Taylor, R. K., and Kull, F. J. (2010) Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes. Proc. Natl. Acad. Sci. U. S. A. 107, 2860-2865
36. Sali, A., Potterton, L., Yuan, F., van Vlijmen, H., and Karplus, M. (1995) Evaluation of comparative protein modeling by MODELLER. Proteins 23, 318-326
37. Laskowski, R. A., MacArthur, M. W., Moss, D. S., and Thornton, J. M. (1993) PROCHECK. A program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26, 283-291
38. Jain, A. N. (2003) Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine. J. Med. Chem. 46, 499-511
39. Pittard, J., Camakaris, H., and Yang, J. (2005) The TyrR regulon. Mol. Microbiol. 55, 16-26
40. Yang, J., Dogovski, C., Hocking, D., Tauschek, M., Perugini, M., and Robins-Browne, R. M. (2009) Bicarbonate-mediated stimulation of RegA, the global virulence regulator from Citrobacter rodentium. J. Mol. Biol. 394, 591-599
41. Levy, S. B., and Marshall, B. (2004) Antibacterial resistance worldwide. Causes, challenges, and responses. Nat. Med. 10, S122-S129
42. Wong, C. S., Jelacic, S., Habeeb, R. L., Watkins, S. L., and Tarr, P. I. (2000) The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N. Engl. J. Med. 342, 1930-1936
43. Kollef, M. H., Golan, Y., Micek, S. T., Shorr, A. F., and Restrepo, M. I. (2011) Appraising contemporary strategies to combat multidrug resistant gram-negative bacterial infections. Proceedings and data from the Gramnegative resistance summit. Clin. Infect. Dis. 53, S33-S55
44. Talbot, G. H., Bradley, J., Edwards, J. E., Jr., Gilbert, D., Scheld, M., and Bartlett, J. G. (2006) Bad bugs need drugs. An update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin. Infect. Dis. 42, 657-668
45. Stanton, T. B. (2013) A call for antibiotic alternatives research. Trends Microbiol. 21, 111-113
46. Sun, F., Zhou, L., Zhao, B. C., Deng, X., Cho, H., Yi, C., Jian, X., Song, C. X., Luan, C. H., Bae, T., Li, Z., and He, C. (2011) Targeting MgrA-mediated virulence regulation in Staphylococcus aureus. Chem. Biol. 18, 1032-1041
47. Hung, D. T., Shakhnovich, E. A., Pierson, E., and Mekalanos, J. J. (2005) Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization. Science 310, 670-674
48. Kimura, K., Iwatsuki, M., Nagai, T., Matsumoto, A., Takahashi, Y., Shiomi, K., Omura, S., and Abe, A. (2011) A small-molecule inhibitor of the bacterial type III secretion system protects against in vivo infection with Citrobacter rodentium. J. Antibiot. 64, 197-203
49. Garrity-Ryan, L. K., Kim, O. K., Balada-Llasat, J. M., Bartlett, V. J., Verma, A. K., Fisher, M. L., Castillo, C., Songsungthong, W., Tanaka, S. K., Levy, S. B., Mecsas, J., and Alekshun, M. N. (2010) Small molecule inhibitors of LcrF, a Yersinia pseudotuberculosis transcription factor, attenuate virulence and limit infection in a murine pneumonia model. Infect. Immun. 78, 4683-4690
50. Gauthier, A., Puente, J. L., and Finlay, B. B. (2003) Secretin of the enteropathogenic Escherichia coli type III secretion system requires components of the type III apparatus for assembly and localization. Infect. Immun. 71, 3310-3319
51. Rasko, D. A., Moreira, C. G., Li de, R., Reading, N. C., Ritchie, J. M., Waldor, M. K., Williams, N., Taussig, R., Wei, S., Roth, M., Hughes, D. T., Huntley, J. F., Fina, M. W., Falck, J. R., and Sperandio, V. (2008) Targeting QseC signaling and virulence for antibiotic development. Science 321, 1078-1080
52. Shakhnovich, E. A., Hung, D. T., Pierson, E., Lee, K., and Mekalanos, J. J. (2007) Virstatin inhibits dimerization of the transcriptional activator ToxT. Proc. Natl. Acad. Sci. U. S. A. 104, 2372-2377
53. Childers, B. M., Weber, G. G., Prouty, M. G., Castaneda, M. M., Peng, F., and Klose, K. E. (2007) Identification of residues critical for the function of the Vibrio cholerae virulence regulator ToxT by scanning alanine mutagenesis. J. Mol. Biol. 367, 1413-1430
54. Chang, J. Y., Antonopoulos, D. A., Kalra, A., Tonelli, A., Khalife, W. T., Schmidt, T. M., and Young, V. B. (2008) Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J. Infect. Dis. 197, 435-438
55. Blaser, M. (2011) Antibiotic overuse. Stop the killing of beneficial bacteria. Nature 476, 393-394
56. Sheikh, J., Czeczulin, J. R., Harrington, S., Hicks, S., Henderson, I. R., Le Bouguénec, C., Gounon, P., Phillips, A., and Nataro, J. P. (2002) A novel dispersin protein in enteroaggregative Escherichia coli. J. Clin. Invest. 110, 1329-1337
57. Lee, J. H., and Isaacson, R. E. (1995) Expression of the gene cluster associated with the Escherichia coli pilus adhesin K99. Infect. Immun. 63, 4143-4149
58. Deng, W., Vallance, B. A., Li, Y., Puente, J. L., and Finlay, B. B. (2003) Citrobacter rodentium translocated intimin receptor (Tir) is an essential virulence factor needed for actin condensation, intestinal colonization, and colonic hyperplasia in mice. Mol. Microbiol. 48, 95-115
59. Croxen, M. A., and Finlay, B. B. (2010) Molecular mechanisms of Escherichia coli pathogenicity. Nat. Rev. Microbiol. 8, 26-38
60. Koya, G., Kosakai, N., Kono, M., Mori, M., and Fukasawa, Y. (1954) Observations on the multiplication of Escherichia coli 0-111 B4 in the intestinal tract of adult volunteers in feeding experiments, the intubation study with Miller-Abbott's double lumen tube. Jpn. J. Med. Sci. Biol. 7, 197-203
61. Mekalanos, J. J. (1992) Environmental signals controlling expression of virulence determinants in bacteria. J. Bacteriol. 174, 1-7
62. Buchholz, U., Bernard, H., Werber, D., Böhmer, M. M., Remschmidt, C., Wilking, H., Deleré, Y., an der Heiden, M., Adlhoch, C., Dreesman, J., Ehlers, J., Ethelberg, S., Faber, M., Frank, C., Fricke, G., Greiner, M., Höhle, M., Ivarsson, S., Jark, U., Kirchner, M., Koch, J., Krause, G., Luber, P., Rosner, B., Stark, K., and Kühne, M. (2011) German outbreak of Escherichia coli O104:H4 associated with sprouts. N. Engl. J. Med. 365, 1763-1770