An in vivo high-throughput screening approach targeting the type IV secretion system component VirB8 identified inhibitors of Brucella abortus 2308 proliferation

Infection and Immunity

Volumn 79, Issue 3, 2011, Pages 1033-1043

  Paschos, Athanasios ^a   Den Hartigh, Andreas ^b   Smith, Mark A ^c   Atluri, Vidya L ^b   Sivanesan, Durga ^c   Tsolis, Renée M ^b   Baron, Christian ^c  

^a MCMASTER UNIVERSITY   (Canada)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; B8I1; B8I10; B8I11; B8I12; B8I13; B8I14; B8I15; B8I16; B8I17; B8I18; B8I19; B8I2; B8I20; B8I3; B8I4; B8I5; B8I6; B8I7; B8I8; B8I9; BACTERIAL PROTEIN; BTB 01692; GK 02122; PROTEIN VIRB8; SEW 05753; SPB 05636; UNCLASSIFIED DRUG; XBX 00150;

ANIMAL CELL; ARTICLE; BACTERIAL GENE; BRUCELLA ABORTUS; CONTROLLED STUDY; DRUG DETERMINATION; DRUG STRUCTURE; DRUG TARGETING; MACROPHAGE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN INTERACTION; SCREENING; TYPE IV SECRETION SYSTEM;

EID: 79952287929     PISSN: 00199567     EISSN: 10985522     Source Type: Journal    
DOI: 10.1128/IAI.00993-10     Document Type: Article

References (52)

1. Altman, E., and G. Segal. 2008. The response regulator CpxR directly regulates expression of several Legionella pneumophila icm/dot components as well as new translocated substrates. J. Bacteriol. 190:1985-1996. (Pubitemid 351355321)
2. Ariza, J., et al. 2007. Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations. PLoS Med. 4:e317.
3. Backert, S., and T. F. Meyer. 2006. Type IV secretion systems and their effectors in bacterial pathogenesis. Curr. Opin. Microbiol. 9:207-217.
4. Baron, C. 2010. Antivirulence drugs to target bacterial secretion systems. Curr. Opin. Microbiol. 13:100-105.
5. Baron, C. 2005. From bioremediation to biowarfare: on the impact and mechanism of type IV secretion systems. FEMS Microbiol. Lett. 253:163-170.
6. Baron, C. 2006. VirB8: a conserved type IV secretion system assembly factor and drug target. Biochem. Cell Biol. 84:890-899.
7. Baron, C., and B. Coombes. 2007. Targeting bacterial secretion systems: benefits of disarmament in the microcosm. Infect. Disord. Drug Targets 7:19-27.
8. Bayliss, R., et al. 2007. NMR structure of a complex between the VirB9/ VirB7 interaction domains of the pKM101 type IV secretion system. Proc. Natl. Acad. Sci. U. S. A. 104:1673-1678.
9. Begg, Y. A., J. N. Whyte, and B. A. Haddock. 1977. The identification of mutants of Escherichia coli deficient in formate dehydrogenase and nitrate reductase activities using dye indicator plates. FEMS Microbiol. Lett. 2:47-50.
10. Boschiroli, M. L., V. Foulongne, and D. O'Callaghan. 2001. Brucellosis: a worldwide zoonosis. Curr. Opin. Microbiol. 4:58-64.
11. Cascales, E., and P. J. Christie. 2004. Definition of a bacterial type IV secretion pathway for a DNA substrate. Science 304:1170-1173.
12. Celli, J., and J. P. Gorvel. 2004. Organelle robbery: Brucella interactions with the endoplasmic reticulum. Curr. Opin. Microbiol. 7:93-97.
13. Chandran, V., et al. 2009. Structure of the outer membrane complex of a type IV secretion system. Nature 29:29.
14. Charpentier, X., et al. 2009. Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila. PLoS Pathog. 5:e1000501.
15. Christie, P. J., K. Atmakuri, V. Krishnamoorthy, S. Jakubowski, and E. Cascales. 2005. Biogenesis, architecture, and function of bacterial type IV secretion systems. Annu. Rev. Microbiol. 59:415-485.
16. Clatworthy, A. E., E. Pierson, and D. T. Hung. 2007. Targeting virulence: a new paradigm for antimicrobial therapy. Nat. Chem. Biol. 3:541-548.
17. Cowie, A., et al. 2006. An integrated approach to functional genomics: construction of a novel reporter gene fusion library for Sinorhizobium meliloti. Appl. Environ. Microbiol. 72:7156-7167. (Pubitemid 44748429)
18. Das, A., and Y.-H. Xie. 2000. The Agrobacterium T-DNA transport pore proteins VirB8, VirB9 and VirB10 interact with one another. J. Bacteriol. 182:758-763.
19. Delrue, R. M., et al. 2005. A quorum-sensing regulator controls expression of both the type IV secretion system and the flagellar apparatus of Brucella melitensis. Cell. Microbiol. 7:1151-1161.
20. den Hartigh, A. B., H. G. Rolan, M. F. de Jong, and R. M. Tsolis. 2008. VirB3 to VirB6 and VirB8 to VirB11, but not VirB7, are essential for mediating persistence of Brucella in the reticuloendothelial system. J. Bacteriol. 190: 4427-4436.
21. den Hartigh, A. B., et al. 2004. Differential requirements for VirB1 and VirB2 during Brucella abortus infection. Infect. Immun. 72:5143-5149.
22. Felise, H. B., et al. 2008. An inhibitor of gram-negative bacterial virulence protein secretion. Cell Host Microbe 4:325-336.
23. Fernandez-Lopez, R., et al. 2005. Unsaturated fatty acids are inhibitors of bacterial conjugation. Microbiology 151:3517-3526. (Pubitemid 41632065)
24. Fronzes, R., P. J. Christie, and G. Waksman. 2009. The structural biology of type IV secretion systems. Nat. Rev. Microbiol. 7:703-714.
25. Fronzes, R., et al. 2009. Structure of a type IV secretion system core complex. Science 323:266-268.
26. Gomis-Rüth, F. X., et al. 2001. The bacterial conjugation protein TrwB resembles ring helicases and F1-ATPase. Nature 409:637-641. (Pubitemid 32154818)
27. Hare, S., R. Bayliss, C. Baron, and G. Waksman. 2006. A large domain swap in the VirB11 ATPase of Brucella suis leaves the hexameric assembly intact. J. Mol. Biol. 360:56-66.
28. Hilleringmann, M., et al. 2006. Inhibitors of Helicobacter pylori ATPase Cagalpha block CagA transport and cag virulence. Microbiology 152:2919-2930. (Pubitemid 44542373)
29. Hughes, D. 2003. Exploiting genomics, genetics and chemistry to combat antibiotic resistance. Nat. Rev. Genet. 4:432-441.
30. Hung, D. T., E. A. Shakhnovich, E. Pierson, and J. J. Mekalanos. 2005. Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization. Science 310:670-674.
31. Judd, P. K., R. B. Kumar, and A. Das. 2005. Spatial location and requirements for the assembly of the Agrobacterium tumefaciens type IV secretion apparatus. Proc. Natl. Acad. Sci. U. S. A. 102:11498-11503.
32. Karimova, G., Nathalie Dautin, and Daniel Ladant. 2005. Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis. J. Bacteriol. 187:2233-2243.
33. Kauppi, A. M., R. Nordfelth, H. Uvell, H. Wolf-Watz, and M. Elofsson. 2003. Targeting bacterial virulence: inhibitors of type III secretion in Yersinia. Chem. Biol. 10:241-249.
34. Keyser, P., M. Elofsson, S. Rosell, and H. Wolf-Watz. 2008. Virulence blockers as alternatives to antibiotics: type III secretion inhibitors against Gram-negative bacteria. J. Intern. Med. 264:17-29.
35. Kulakov, Y. K., P. G. Guigue-Talet, M. R. Ramuz, and D. O'Callaghan. 1997. Response of Brucella suis 1330 and B. canis RM6/66 to growth at acid pH and induction of an adaptive acid tolerance response. Res. Microbiol. 148: 145-151.
36. Levy, S. B., and B. Marshall. 2004. Antibacterial resistance worldwide: causes, challenges and responses. Nat. Med. 10:S122-S129.
37. Muschiol, S., et al. 2006. A small-molecule inhibitor of type III secretion inhibits different stages of the infectious cycle of Chlamydia trachomatis. Proc. Natl. Acad. Sci. U. S. A. 103:14566-14571. (Pubitemid 44484790)
38. Negrea, A., et al. 2007. Salicylidene acylhydrazides that affect type III protein secretion in Salmonella enterica serovar typhimurium. Antimicrob. Agents Chemother. 51:2867-2876.
39. Nordfelth, R., A. M. Kauppi, H. A. Norberg, H. Wolf-Watz, and M. Elofsson. 2005. Small-molecule inhibitors specifically targeting type III secretion. Infect. Immun. 73:3104-3114.
40. Paschos, A., et al. 2006. Dimerization and interactions of Brucella suis VirB8 with VirB4 and VirB10 are required for its biological activity. Proc. Natl. Acad. Sci. U. S. A. 103:7252-7257.
41. Patey, G., Z. Qi, G. Bourg, C. Baron, and D. O'Callaghan. 2006. Swapping of periplasmic domains between Brucella suis VirB8 and pSB102 VirB8 homologue allows heterologous complementation. Infect. Immun. 74:4945-4949.
42. Rambow-Larsen, A. A., E. M. Petersen, C. R. Gourley, and G. A. Splitter. 2009. Brucella regulators: self-control in a hostile environment. Trends Microbiol. 17:371-377.
43. Seleem, M. N., S. M. Boyle, and N. Sriranganathan. 2010. Brucellosis: a re-emerging zoonosis. Vet. Microbiol. 140:392-398.
44. Sivanesan, D., M. A. Hancock, A. M. Villamil Giraldo, and C. Baron. 2010. Quantitative analysis of VirB8-VirB9-VirB10 interactions provides a dynamic model of type IV secretion system core complex assembly. Biochemistry 49:4483-4493.
45. Terradot, L., et al. 2005. Crystal structures of the periplasmic domains of two core subunits of the bacterial type IV secretion system, VirB8 from Brucella suis and ComB10 from Helicobacter pylori. Proc. Natl. Acad. Sci. U. S. A. 102:4596-4601. (Pubitemid 40397157)
46. Veenendaal, A. K., C. Sundin, and A. J. Blocker. 2009. Small-molecule type III secretion system inhibitors block assembly of the Shigella type III secreton. J. Bacteriol. 191:563-570.
47. Walsh, C. 2003. Where will new antibiotics come from? Nat. Rev. Microbiol. 1:65-70.
48. Yagupsky, P., and E. J. Baron. 2005. Laboratory exposures to brucellae and implications for bioterrorism. Emerg. Infect. Dis. 11:1180-1185.
49. Yeo, H.-J., Q. Yuan, M. R. Beck, C. Baron, and G. Waksman. 2003. Structural and functional characterization of the VirB5 protein from the type IV secretion system encoded by the conjugative plasmid pKM101. Proc. Natl. Acad. Sci. U. S. A. 100:15947-15962.
50. Yeo, H. J., S. N. Savvides, A. B. Herr, E. Lanka, and G. Waksman. 2000. Crystal structure of the hexameric traffic ATPase of the Helicobacter pylori type IV secretion system. Mol. Cell 6:1461-1472. (Pubitemid 32045937)
51. Young, E. J. 1995. An overview of human brucellosis. Clin. Infect. Dis. 21:283-289.
52. Zhang, J. H., T. D. Chung, and K. R. Oldenburg. 1999. A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J. Biomol. Screen. 4:67-73.