Small-molecule inhibitor of the shigella flexneri master virulence regulator VirF

Infection and Immunity

Volumn 81, Issue 11, 2013, Pages 4220-4231

  Koppolu, Veerendra ^a   Osaka, Ichie ^a   Skredenske, Jeff M ^a   Kettle, Bria ^a   Hefty, P Scott ^a   Li, Jiaqin ^a   Egan, Susan M ^a  

^a UNIVERSITY OF KANSAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPICILLIN; ANTIBIOTIC AGENT; ARAC PROTEIN; BACTERIAL PROTEIN; COMPLEMENTARY DNA; DNA; GENTAMICIN; KANAMYCIN; MESSENGER RNA; NALIDIXIC ACID; PROTEIN VIRF; SE 1; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL GENE; BACTERIAL GROWTH; BACTERIAL VIRULENCE; BACTERIUM CULTURE; CONTROLLED STUDY; DNA BINDING; ESCHERICHIA COLI; GENE EXPRESSION; HOST CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FAMILY; REAL TIME POLYMERASE CHAIN REACTION; REPORTER GENE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SHIGELLA FLEXNERI; TRANSCRIPTION INITIATION; TYPE III SECRETION SYSTEM;

EID: 84886770381     PISSN: 00199567     EISSN: 10985522     Source Type: Journal    
DOI: 10.1128/IAI.00919-13     Document Type: Article

References (98)

1. Jennison AV, Verma NK. 2004. Shigella flexneri infection: pathogenesis and vaccine development. FEMS Microbiol. Rev. 28:43-58.
2. Kotloff KL, Winickoff JP, Ivanoff B, Clemens JD, Swerdlow DL, Sansonetti PJ, Adak GK, Levine MM. 1999. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull. World Health Organ. 77:651-666.
3. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O'Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM. 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382:209-222.
4. DuPont HL, Levine MM, Hornick RB, Formal SB. 1989. Inoculum size in shigellosis and implications for expected mode of transmission. J. Infect. Dis. 159:1126-1128.
5. Sansonetti PJ, Kopecko DJ, Formal SB. 1982. Involvement of a plasmid in the invasive ability of Shigella flexneri. Infect. Immun. 35:852-860.
6. Blocker A, Jouihri N, Larquet E, Gounon P, Ebel F, Parsot C, Sansonetti P, Allaoui A. 2001. Structure and composition of the Shigella flexneri "needle complex", a part of its type III secreton. Mol. Microbiol. 39:652- 663.
7. High N, Mounier J, Prevost MC, Sansonetti PJ. 1992. IpaB of Shigella flexneri causes entry into epithelial cells and escape from the phagocytic vacuole. EMBO J. 11:1991-1999.
8. Zychlinsky A, Kenny B, Menard R, Prevost MC, Holland IB, Sansonetti PJ. 1994. IpaB mediates macrophage apoptosis induced by Shigella flexneri. Mol. Microbiol. 11:619-627.
9. Sakai T, Sasakawa C, Yoshikawa M. 1988. Expression of four virulence antigens of Shigella flexneri is positively regulated at the transcriptional level by the 30 kilodalton VirF protein. Mol. Microbiol. 2:589-597.
10. Tran CN, Giangrossi M, Prosseda G, Brandi A, Di Martino ML, Colonna B, Falconi M. 2011. A multifactor regulatory circuit involving H-NS, VirF and an antisense RNA modulates transcription of the virulence gene icsA of Shigella flexneri. Nucleic Acids Res. 39:8122-8134.
11. Tobe T, Yoshikawa M, Mizuno T, Sasakawa C. 1993. Transcriptional control of the invasion regulatory gene virB of Shigella flexneri: activation by VirF and repression by H-NS. J. Bacteriol. 175:6142-6149.
12. Sakai T, Sasakawa C, Makino S, Kamata K, Yoshikawa M. 1986. Molecular cloning of a genetic determinant for Congo red binding ability which is essential for the virulence of Shigella flexneri. Infect. Immun. 51:476-482.
13. DuPont HL, Hornick RB, Snyder MJ, Libonati JP, Formal SB, Gangarosa EJ. 1972. Immunity in shigellosis. I. Response of man to attenuated strains of Shigella. J. Infect. Dis. 125:5-11.
14. Mel DM, Terzin AL, Vuksic L. 1965. Studies on vaccination against bacillary dysentery. 3. Effective oral immunization against Shigella flexneri 2a in a field trial. Bull. World Health Organ. 32:647-655.
15. Sansonetti PJ, Arondel J, Fontaine A, d'Hauteville H, Bernardini ML. 1991. ompB (osmo-regulation) and icsA (cell-to-cell spread) mutants of Shigella flexneri: vaccine candidates and probes to study the pathogenesis of shigellosis. Vaccine 9:416-422.
16. Dentchev V, Marinova S, Vassilev T, Bratoyeva M, Linde K. 1990. Live Shigella flexneri 2a and Shigella sonnei I vaccine candidate strains with two attenuating markers. II. Preliminary results of vaccination of adult volunteers and children aged 2-17 years. Vaccine 8:30-34.
17. Pickering LK. 2004. Antimicrobial resistance among enteric pathogens. Semin. Pediatr. Infect. Dis. 15:71-77.
18. Walsh C. 2003. Where will new antibiotics come from? Nat. Rev. Microbiol. 1:65-70.
19. Coates A, Hu Y, Bax R, Page C. 2002. The future challenges facing the development of new antimicrobial drugs. Nat. Rev. Drug Discov. 1:895- 910.
20. Projan SJ, Bradford PA. 2007. Late stage antibacterial drugs in the clinical pipeline. Curr. Opin. Microbiol. 10:441-446.
21. Talbot GH, Bradley J, Edwards JE, Jr, Gilbert D, Scheld M, Bartlett JG, Antimicrobial Availability Task Force of the Infectious Diseases Society of America. 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.
22. Rasko DA, Sperandio V. 2010. Anti-virulence strategies to combat bacteria- mediated disease. Nat. Rev. Drug Discov. 9:117-128.
23. Blaser M. 2011. Antibiotic overuse: stop the killing of beneficial bacteria. Nature 476:393-394.
24. Champion GA, Neely MN, Brennan MA, DiRita VJ. 1997. A branch in the ToxR regulatory cascade of Vibrio cholerae revealed by characterization of toxT mutant strains. Mol. Microbiol. 23:323-331.
25. Coburn PS, Baghdayan AS, Dolan GT, Shankar N. 2008. An AraC-type transcriptional regulator encoded on the Enterococcus faecalis pathogenicity island contributes to pathogenesis and intracellular macrophage survival. Infect. Immun. 76:5668-5676.
26. Casaz P, Garrity-Ryan LK, McKenney D, Jackson C, Levy SB, Tanaka SK, Alekshun MN. 2006. MarA, SoxS and Rob function as virulence factors in an Escherichia coli murine model of ascending pyelonephritis. Microbiology 152:3643-3650.
27. Frota CC, Papavinasasundaram KG, Davis EO, Colston MJ. 2004. The AraC family transcriptional regulator Rv1931c plays a role in the virulence of Mycobacterium tuberculosis. Infect. Immun. 72:5483-5486.
28. Hauser AR, Kang PJ, Engel JN. 1998. PepA, a secreted protein of Pseudomonas aeruginosa, is necessary for cytotoxicity and virulence. Mol. Microbiol. 27:807-818.
29. Gallegos MT, Schleif R, Bairoch A, Hofmann K, Ramos JL. 1997. AraC/XylS family of transcriptional regulators. Microbiol. Mol. Biol. Rev. 61:393-410.
30. Ibarra JA, Perez-Rueda E, Segovia L, Puente JL. 2008. The DNA-binding domain as a functional indicator: the case of the AraC/XylS family of transcription factors. Genetica 133:65-76.
31. Flashner Y, Mamroud E, Tidhar A, Ber R, Aftalion M, Gur D, Lazar S, Zvi A, Bino T, Ariel N, Velan B, Shafferman A, Cohen S. 2004. Generation of Yersinia pestis attenuated strains by signature-tagged mutagenesis in search of novel vaccine candidates. Infect. Immun. 72:908- 915.
32. Hughes D. 2003. Exploiting genomics, genetics and chemistry to combat antibiotic resistance. Nat. Rev. Genet. 4:432-441.
33. Knowles DJ. 1997. New strategies for antibacterial drug design. Trends Microbiol. 5:379-383.
34. Schmidt FR. 2004. The challenge of multidrug resistance: actual strategies in the development of novel antibacterials. Appl. Microbiol. Biotechnol. 63:335-343.
35. Buchrieser C, Glaser P, Rusniok C, Nedjari H, D'Hauteville H, Kunst F, Sansonetti P, Parsot C. 2000. The virulence plasmid pWR100 and the repertoire of proteins secreted by the type III secretion apparatus of Shigella flexneri. Mol. Microbiol. 38:760-771.
36. Falconi M, Colonna B, Prosseda G, Micheli G, Gualerzi CO. 1998. Thermoregulation of Shigella and Escherichia coli EIEC pathogenicity. A temperature-dependent structural transition of DNA modulates accessibility of virF promoter to transcriptional repressor H-NS. EMBO J. 17: 7033-7043.
37. Tobe T, Nagai S, Okada N, Adler B, Yoshikawa M, Sasakawa C. 1991. Temperature-regulated expression of invasion genes in Shigella flexneri is controlled through the transcriptional activation of the virB gene on the large plasmid. Mol. Microbiol. 5:887-893.
38. Prosseda G, Fradiani PA, Di Lorenzo M, Falconi M, Micheli G, Casalino M, Nicoletti M, Colonna B. 1998. A role for H-NS in the regulation of the virF gene of Shigella and enteroinvasive Escherichia coli. Res. Microbiol. 149:15-25.
39. Porter ME, Dorman CJ. 1997. Differential regulation of the plasmidencoded genes in the Shigella flexneri virulence regulon. Mol. Gen. Genet. 256:93-103.
40. Durand J.M., Dagberg B, Uhlin BE, Björk GR. 2000. Transfer RNA modification, temperature and DNA superhelicity have a common target in the regulatory network of the virulence of Shigella flexneri: the expression of the virF gene. Mol. Microbiol. 35:924-935.
41. Porter ME, Dorman CJ. 1994. A role for H-NS in the thermo-osmotic regulation of virulence gene expression in Shigella flexneri. J. Bacteriol. 176:4187-4191.
42. Sasakawa C, Komatsu K, Tobe T, Suzuki T, Yoshikawa M. 1993. Eight genes in region 5 that form an operon are essential for invasion of epithelial cells by Shigella flexneri 2a. J. Bacteriol. 175:2334-2346.
43. Dorman CJ. 1992. The VirF protein from Shigella flexneri is a member of the AraC transcription factor superfamily and is highly homologous to Rns, a positive regulator of virulence genes in enterotoxigenic Escherichia coli. Mol. Microbiol. 6:1575-1576.
44. Dorman CJ, Porter ME. 1998. The Shigella virulence gene regulatory cascade: a paradigm of bacterial gene control mechanisms. Mol. Microbiol. 29:677-684.
45. Egile C, Loisel TP, Laurent V, Li R, Pantaloni D, Sansonetti PJ, Carlier MF. 1999. Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility. J. Cell Biol. 146:1319-1332.
46. Suzuki T, Miki H, Takenawa T, Sasakawa C. 1998. Neural Wiskott- Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri. EMBO J. 17:2767-2776.
47. Suzuki T, Mimuro H, Suetsugu S, Miki H, Takenawa T, Sasakawa C. 2002. Neural Wiskott-Aldrich syndrome protein (N-WASP) is the specific ligand for Shigella VirG among the WASP family and determines the host cell type allowing actin-based spreading. Cell. Microbiol. 4:223-233.
48. Goldberg MB. 1997. Shigella actin-based motility in the absence of vinculin. Cell Motil. Cytoskeleton 37:44-53.
49. Beloin C, Dorman CJ. 2003. An extended role for the nucleoid structuring protein H-NS in the virulence gene regulatory cascade of Shigella flexneri. Mol. Microbiol. 47:825-838.
50. Kane CD, Schuch R, Day WA, Jr, Maurelli AT. 2002. MxiE regulates intracellular expression of factors secreted by the Shigella flexneri 2a type III secretion system. J. Bacteriol. 184:4409-4419.
51. Blocker A, Gounon P, Larquet E, Niebuhr K, Cabiaux V, Parsot C, Sansonetti P. 1999. The tripartite type III secreton of Shigella flexneri inserts IpaB and IpaC into host membranes. J. Cell Biol. 147:683-693.
52. Tran Van Nhieu G, Caron E, Hall A, Sansonetti PJ. 1999. IpaC induces actin polymerization and filopodia formation during Shigella entry into epithelial cells. EMBO J. 18:3249-3262.
53. Chen Y, Smith MR, Thirumalai K, Zychlinsky A. 1996. A bacterial invasin induces macrophage apoptosis by binding directly to ICE. EMBO J. 15:3853-3860.
54. Ménard R, Sansonetti P, Parsot C. 1994. The secretion of the Shigella flexneri Ipa invasins is activated by epithelial cells and controlled by IpaB and IpaD. EMBO J. 13:5293-5302.
55. Ogawa M, Yoshimori T, Suzuki T, Sagara H, Mizushima N, Sasakawa C. 2005. Escape of intracellular Shigella from autophagy. Science 307:727- 731.
56. Kayath CA, Hussey S, El hajjami N, Nagra K, Philpott D, Allaoui A. 2010. Escape of intracellular Shigella from autophagy requires binding to cholesterol through the type III effector, IcsB. Microbes Infect. 12:956- 966.
57. Sasakawa C, Kamata K, Sakai T, Makino S, Yamada M, Okada N, Yoshikawa M. 1988. Virulence-associated genetic regions comprising 31 kilobases of the 230-kilobase plasmid in Shigella flexneri 2a. J. Bacteriol. 170:2480-2484.
58. Mills JA, Venkatesan MM, Baron LS, Buysse JM. 1992. Spontaneous insertion of an IS1-like element into the virF gene is responsible for avirulence in opaque colonial variants of Shigella flexneri 2a. Infect. Immun. 60:175-182.
59. Hurt JK, McQuade TJ, Emanuele A, Larsen MJ, Garcia GA. 2010. High-throughput screening of the virulence regulator VirF: a novel antibacterial target for shigellosis. J. Biomol. Screen. 15:379-387.
60. Skredenske JM, Koppolu V, Kolin A, Deng J, Kettle B, Taylor B, Egan SM. 2013. Identification of a small molecule inhibitor of bacterial AraC family activators. J. Biomol. Screen. 18:588-598.
61. Stewart GS, Lubinsky-Mink S, Jackson CG, Cassel A, Kuhn J. 1986. pHG165: a pBR322 copy number derivative of pUC8 for cloning and expression. Plasmid 15:172-181.
62. Backman K, Chen Y-M, Magasanik B. 1981. Physical and genetic characterization of the glnA-glnG region of the Escherichia coli chromosome. Proc. Natl. Acad. Sci. U. S. A. 78:3743-3747.
63. Miller JH. 1972. Experiments in molecular genetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
64. Bhende PM, Egan SM. 1999. Amino acid-DNA contacts by RhaS: an AraC family transcription activator. J. Bacteriol. 181:5185-5192.
65. Gottesman ME, Yarmolinsky MB. 1968. The integration and excision of the bacteriophage lambda genome. Cold Spring Harbor Symp. Quant. Biol. 33:735-747.
66. Jubete Y, Maurizi MR, Gottesman S. 1996. Role of the heat shock protein DnaJ in the Lon-dependent degradation of naturally unstable proteins. J. Biol. Chem. 271:30798-30803.
67. Wickstrum JR, Skredenske JM, Balasubramaniam V, Jones K, Egan SM. 2010. The AraC/XylS family activator RhaS negatively autoregulates rhaSR expression by preventing cyclic AMP receptor protein activation. J. Bacteriol. 192:225-232.
68. Jullien N, Herman JP. 2011. LUEGO: a cost and time saving gel shift procedure. Biotechniques 51:267-269.
69. Pantoliano MW, Petrella EC, Kwasnoski JD, Lobanov VS, Myslik J, Graf E, Carver T, Asel E, Springer BA, Lane P, Salemme FR. 2001. High-density miniaturized thermal shift assays as a general strategy for drug discovery. J. Biomol. Screen. 6:429-440.
70. Ericsson UB, Hallberg BM, Detitta GT, Dekker N, Nordlund P. 2006. Thermofluor-based high-throughput stability optimization of proteins for structural studies. Anal. Biochem. 357:289-298.
71. Senisterra GA, Finerty PJ, Jr. 2009. High throughput methods of assessing protein stability and aggregation. Mol. Biosyst. 5:217-223.
72. Runyen-Janecky L, Dazenski E, Hawkins S, Warner L. 2006. Role and regulation of the Shigella flexneri sit and mntH systems. Infect. Immun. 74:4666-4672.
73. Broach WH, Egan N, Wing HJ, Payne SM, Murphy ER. 2012. VirFindependent regulation of Shigella virB transcription is mediated by the smallRNARyhB. PLoS One 7:e38592. doi:10.1371/journal.pone.0038592.
74. Bore E, Hebraud M, Chafsey I, Chambon C, Skjaeret C, Moen B, Moretro T, Langsrud O, Rudi K, Langsrud S. 2007. Adapted tolerance to benzalkonium chloride in Escherichia coli K-12 studied by transcriptome and proteome analyses. Microbiology 153:935-946.
75. Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2-δδCT method. Methods 25: 402-408.
76. Klimpel GR, Shaban R, Niesel DW. 1990. Bacteria-infected fibroblasts have enhanced susceptibility to the cytotoxic action of tumor necrosis factor. J. Immunol. 145:711-717.
77. Kapasi K, Inman RD. 1992. HLA-B27 expression modulates gramnegative bacterial invasion into transfected L cells. J. Immunol. 148:3554- 3559.
78. Okamura N, Nakaya R. 1977. Rough mutant of Shigella flexneri 2a that penetrates tissue culture cells but does not evoke keratoconjunctivitis in guinea pigs. Infect. Immun. 17:4-8.
79. Sandlin RC, Goldberg MB, Maurelli AT. 1996. Effect of O side-chain length and composition on the virulence of Shigella flexneri 2a. Mol. Microbiol. 22:63-73.
80. Elsinghorst EA. 1994. Measurement of invasion by gentamicin resistance. Methods Enzymol. 236:405-420.
81. Willard HH, Merritt LL, Dean JA. 1965. Instrumental methods of analysis, 4th ed, p 94-95. Van Nostrand, Princeton, NJ.
82. Rees DC, Congreve M, Murray CW, Carr R. 2004. Fragment-based lead discovery. Nat. Rev. Drug Discov. 3:660-672.
83. Nguyen CC, Saier MH, Jr. 1995. Phylogenetic, structural and functional analyses of the LacI-GalR family of bacterial transcription factors. FEBS Lett. 377:98-102.
84. Swint-Kruse L, Matthews KS. 2009. Allostery in the LacI/GalR family: variations on a theme. Curr. Opin. Microbiol. 12:129-137.
85. Körner H, Sofia HJ, Zumft WG. 2003. Phylogeny of the bacterial superfamily of Crp-Fnr transcription regulators: exploiting the metabolic spectrum by controlling alternative gene programs. FEMS Microbiol. Rev. 27:559-592.
86. Niesen FH, Berglund H, Vedadi M. 2007. The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat. Protoc. 2:2212-2221.
87. Lo MC, Aulabaugh A, Jin G, Cowling R, Bard J, Malamas M, Ellestad G. 2004. Evaluation of fluorescence-based thermal shift assays for hit identification in drug discovery. Anal. Biochem. 332:153-159.
88. Chi G, Manos-Turvey A, O'Connor PD, Johnston JM, Evans GL, Baker EN, Payne RJ, Lott JS, Bulloch EM. 2012. Implications of binding mode and active site flexibility for inhibitor potency against the salicylate synthase from Mycobacterium tuberculosis. Biochemistry 51:4868-4879.
89. Hau JC, Fontana P, Zimmermann C, De Pover A, Erdmann D, Chene P. 2011. Leveraging the contribution of thermodynamics in drug discovery with the help of fluorescence-based thermal shift assays. J. Biomol. Screen 16:552-556.
90. Allaoui A, Menard R, Sansonetti PJ, Parsot C. 1993. Characterization of the Shigella flexneri ipgD and ipgF genes, which are located in the proximal part of the mxi locus. Infect. Immun. 61:1707-1714.
91. Pendaries C, Tronchere H, Arbibe L, Mounier J, Gozani O, Cantley L, Fry MJ, Gaits-Iacovoni F, Sansonetti PJ, Payrastre B. 2006. PtdIns5P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri infection. EMBO J. 25:1024-1034.
92. Niebuhr K, Giuriato S, Pedron T, Philpott DJ, Gaits F, Sable J, Sheetz MP, Parsot C, Sansonetti PJ, Payrastre B. 2002. Conversion of PtdIns(4,5)P2 into PtdIns(5)P by the Shigella flexneri effector IpgD reorganizes host cell morphology. EMBO J. 21:5069-5078.
93. Nakayama GR, Caton MC, Nova MP, Parandoosh Z. 1997. Assessment of the Alamar Blue assay for cellular growth and viability in vitro. J. Immunol. Methods 204:205-208.
94. Maloy SR, Stewart VJ, Taylor RK. 1996. Genetic analysis of pathogenic bacteria: a laboratory manual. Cold Spring Harbor Laboratory Press, Plainview, NY.
95. Schroeder GN, Hilbi H. 2008. Molecular pathogenesis of Shigella spp.: controlling host cell signaling, invasion, and death by type III secretion. Clin. Microbiol. Rev. 21:134-156.
96. Schuch R, Sandlin RC, Maurelli AT. 1999. A system for identifying post-invasion functions of invasion genes: requirements for the Mxi-Spa type III secretion pathway of Shigella flexneri in intercellular dissemination. Mol. Microbiol. 34:675-689.
97. Casadaban M. 1976. Transposition and fusion of the lac genes to selected promoters in Escherichia coli using bacteriophage lambda and Mu. J. Mol. Biol. 104:541-555.
98. Silber KR, Keiler KC, Sauer RT. 1992. Tsp: a tail-specific protease that selectively degrades proteins with nonpolar C termini. Proc. Natl. Acad. Sci. U. S. A. 89:295-299.