Identification of a small-molecule inhibitor of bacterial AraC family activators

Journal of Biomolecular Screening

Volumn 18, Issue 5, 2013, Pages 588-598

  Skredenske, Jeff M ^a   Koppolu, Veerendra ^a   Kolin, Ana ^a   Deng, James ^a   Kettle, Bria ^a   Taylor, Byron ^a   Egan, Susan M ^a  

^a UNIVERSITY OF KANSAS   (United States)

Author keywords

antibacterial agents; AraC family activators; cell based assays; high throughput screening; inhibitor

Indexed keywords

ARAC PROTEIN; C REACTIVE PROTEIN; VIRULENCE FACTOR;

ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL GROWTH; BINDING SITE; CONTROLLED STUDY; DNA BINDING; DOSE RESPONSE; DRUG IDENTIFICATION; ENZYME ACTIVITY; GROWTH CURVE; HIGH THROUGHPUT SCREENING; IC 50; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PH; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN PURIFICATION; TRANSCRIPTION INITIATION;

ANTIBACTERIAL AGENTS; ARAC FAMILY ACTIVATORS; CELL-BASED ASSAYS; HIGH-THROUGHPUT SCREENING; INHIBITOR;

ANTI-BACTERIAL AGENTS; ARAC TRANSCRIPTION FACTOR; DNA, BACTERIAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; ESCHERICHIA COLI; ESCHERICHIA COLI PROTEINS; GENE EXPRESSION REGULATION, BACTERIAL; HIGH-THROUGHPUT SCREENING ASSAYS; MICROBIAL SENSITIVITY TESTS; MODELS, BIOLOGICAL; MULTIGENE FAMILY; PROTEIN BINDING; QUINOLINES; SMALL MOLECULE LIBRARIES; TRANS-ACTIVATORS;

EID: 84878203628     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057112474690     Document Type: Article

References (30)

1. Rasko D. A., Sperandio V.. Anti-Virulence Strategies to Combat Bacteria-Mediated Disease. Nat. Rev. Drug Discov. 2010 ; 9: 117-128
2. Gallegos M. T., Schleif R., Bairoch A., Hofmann K., Ramos J. L.. AraC/XylS Family of Transcriptional Regulators. Microbiol. Mol. Biol. Rev. 1997 ; 61: 393-410 (Pubitemid 28006953)
3. Francis M. S., Wolf-Watz H., Forsberg A.. Regulation of Type III Secretion Systems. Curr. Opin. Microbiol. 2002 ; 5: 166-172 (Pubitemid 34289924)
4. Yang J., Tauschek M., Robins-Browne R. M.. Control of Bacterial Virulence by AraC-like Regulators That Respond to Chemical Signals. Trends Microbiol. 2011 ; 19: 128-135
5. Casaz P., Garrity-Ryan L. K., McKenney D., Jackson C., Levy S. B., Tanaka S. K., Alekshun M. N.. MarA, SoxS and Rob Function as Virulence Factors in an Escherichia coli Murine Model of Ascending Pyelonephritis. Microbiology. 2006 ; 152: 3643-3650 (Pubitemid 46040685)
6. Champion G. A., Neely M. N., Brennan M. A., DiRita V. J.. A Branch in the ToxR Regulatory Cascade of Vibrio cholerae Revealed by Characterization of toxT Mutant Strains. Mol. Microbiol. 1997 ; 23: 323-331 (Pubitemid 27049185)
7. Coburn P. S., Baghdayan A. S., Dolan G. T., Shankar N.. An AraC-Type Transcriptional Regulator Encoded on the Enterococcus faecalis Pathogenicity Island Contributes to Pathogenesis and Intracellular Macrophage Survival. Infect. Immun. 2008 ; 76: 5668-5676
8. Darwin A. J., Miller V. L.. Identification of Yersinia enterocolitica Genes Affecting Survival in an Animal Host Using Signature-Tagged Transposon Mutagenesis. Mol. Microbiol. 1999 ; 32: 51-62 (Pubitemid 29164133)
9. Frota C. C., Papavinasasundaram K. G., Davis E. O., Colston M. J.. The AraC Family Transcriptional Regulator Rv1931c Plays a Role in the Virulence of Mycobacterium Tuberculosis. Infect. Immun. 2004 ; 72: 5483-5486 (Pubitemid 39223440)
10. Hauser A. R., Kang P. J., Engel J. N.. PepA, a Secreted Protein of Pseudomonas aeruginosa, Is Necessary for Cytotoxicity and Virulence. Mol. Microbiol. 1998 ; 27: 807-818 (Pubitemid 28081989)
11. Hava D. L., Camilli A.. Large-Scale Identification of Serotype 4 Streptococcus pneumoniae Virulence Factors. Mol. Microbiol. 2002 ; 45: 1389-1406
12. Bowser T. E., Bartlett V. J., Grier M. C., Verma A. K., Warchol T., Levy S. B., Alekshun M. N.. Novel Anti-Infection Agents: Small-Molecule Inhibitors of Bacterial Transcription Factors. Bioorg. Med. Chem. Lett. 2007 ; 17: 5652-5655 (Pubitemid 47391304)
13. 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., et al. Small Molecule Inhibitors of LcrF, a Yersinia pseudotuberculosis Transcription Factor, Attenuate Virulence and Limit Infection in a Murine Pneumonia Model. Infect. Immun. 2010 ; 78: 4683-4690
14. Grier M. C., Garrity-Ryan L. K., Bartlett V. J., Klausner K. A., Donovan P. J., Dudley C., Alekshun M. N., Tanaka S. K., Draper M. P., Levy S. B., et al. N-hydroxybenzimidazole Inhibitors of ExsA MAR Transcription Factor in Pseudomonas aeruginosa: In Vitro Anti-Virulence Activity and Metabolic Stability. Bioorg. Med. Chem. Lett. 2010 ; 20: 3380-3383
15. Hung D. T., Shakhnovich E. A., Pierson E., Mekalanos J. J.. Small-Molecule Inhibitor of Vibrio cholerae Virulence and Intestinal Colonization. Science. 2005 ; 310: 670-674 (Pubitemid 41528158)
16. Hurt J. K., McQuade T. J., Emanuele A., Larsen M. J., Garcia G. A.. High-Throughput Screening of the Virulence Regulator VirF: A Novel Antibacterial Target for Shigellosis. J. Biomol. Screen. 2010 ; 15: 379-387
17. Kim O. K., Garrity-Ryan L. K., Bartlett V. J., Grier M. C., Verma A. K., Medjanis G., Donatelli J. E., Macone A. B., Tanaka S. K., Levy S. B., et al. N-hydroxybenzimidazole Inhibitors of the Transcription Factor LcrF in Yersinia: Novel Antivirulence Agents. J. Med. Chem. 2009 ; 52: 5626-5634
18. Kolin A., Balasubramaniam V., Skredenske J. M., Wickstrum J. R., Egan S. M.. Differences in the Mechanism of the Allosteric l-rhamnose Responses of the AraC/XylS Family Transcription Activators RhaS and RhaR. Mol. Microbiol. 2008 ; 68: 448-461 (Pubitemid 351422965)
19. Alksne L. E., Burgio P., Hu W., Feld B., Singh M. P., Tuckman M., Petersen P. J., Labthavikul P., McGlynn M., Barbieri L., et al. Identification and Analysis of Bacterial Protein Secretion Inhibitors Utilizing a SecA-LacZ Reporter Fusion System. Antimicrob. Agents Chemother. 2000 ; 44: 1418-1427 (Pubitemid 30340773)
20. Zhang J. H., Chung T. D., Oldenburg K. R.. A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J. Biomol. Screen. 1999 ; 4: 67-73 (Pubitemid 29278954)
21. Simons R. W., Houman F., Kleckner N.. Improved Single and Multicopy lac-Based Cloning Vectors for Protein and Operon Fusions. Gene. 1987 ; 53: 85-96 (Pubitemid 17090099)
22. Powell B. S., Rivas M. P., Court D. L., Nakamura Y., Turnbough C. L.. Rapid Confirmation of Single Copy Lambda Prophage Integration by PCR. Nucleic Acids Res. 1994 ; 22: 5765-5766
23. Jubete Y., Maurizi M. R., Gottesman S.. Role of the Heat Shock Protein DnaJ in the Lon-Dependent Degradation of Naturally Unstable Proteins. J. Biol. Chem. 1996 ; 271: 30798-30803 (Pubitemid 26404100)
24. Wickstrum J. R., Egan S. M.. Ni+-Affinity Purification of Untagged cAMP Receptor Protein. Biotechniques. 2002 ; 33: 728-730 (Pubitemid 35168051)
25. Zhan H., Swint-Kruse L., Matthews K. S.. Extrinsic Interactions Dominate Helical Propensity in Coupled Binding and Folding of the Lactose Repressor Protein Hinge Helix. Biochemistry. 2006 ; 45: 5896-5906
26. Wickstrum J. R., Skredenske J. M., Balasubramaniam V., Jones K., Egan S. M.. The AraC/XylS Family Activator RhaS Negatively Autoregulates rhaSR Expression by Preventing Cyclic AMP Receptor Protein Activation. J. Bacteriol. 2010 ; 192: 225-232
27. Wickstrum J. R., Skredenske J. M., Kolin A., Jin D. J., Fang J., Egan S. M.. Transcription Activation by the DNA-Binding Domain of the AraC Family Protein RhaS in the Absence of Its Effector-Binding Domain. J. Bacteriol. 2007 ; 189: 4984-4993 (Pubitemid 47076043)
28. Egan S. M., Schleif R. F.. DNA-Dependent Renaturation of an Insoluble DNA Binding Protein: Identification of the RhaS Binding Site at rhaBAD. J. Mol. Biol. 1994 ; 243: 821-829
29. Zhou P., Wagner G.. Overcoming the Solubility Limit with Solubility-Enhancement Tags: Successful Applications in Biomolecular NMR Studies. J. Biomol. NMR. 2010 ; 46: 23-31
30. Childers B. M., Cao X., Weber G. G., Demeler B., Hart P. J., Klose K. E.. N-terminal Residues of the Vibrio cholerae Virulence Regulatory Protein ToxT Involved in Dimerization and Modulation by Fatty Acids. J. Biol. Chem. 2011 ; 286: 28644-28655