The Bacterial Type III Secretion System as a Target for Developing New Antibiotics

Chemical Biology and Drug Design

Volumn 85, Issue 1, 2015, Pages 30-42

  McShan, Andrew C ^a   De Guzman, Roberto N ^a  

^a UNIVERSITY OF KANSAS   (United States)

Author keywords

antibiotic resistance; antibiotics; salicylidene acylhydrazides; small molecule inhibitors; thiazolidinones; type III secretion system; virulence

Indexed keywords

ANTIBIOTIC AGENT; BENZIMIDAZOLE DERIVATIVE; BILE SALT; CHAPERONE; CHENODEOXYCHOLIC ACID; DEOXYCHOLIC ACID; POLYMER; POLYPEPTIDE; SALICYLALDEHYDE; SALICYLANILIDE DERIVATIVE; SPHINGOLIPID; STEROL DERIVATIVE; STRUCTURAL PROTEIN; THIAZOLE DERIVATIVE; ANTIINFECTIVE AGENT;

ANTIBIOTIC RESISTANCE; ARTICLE; CYTOPLASM; DRUG DESIGN; DRUG FORMULATION; DRUG TARGETING; GENE EXPRESSION; GENE LOCUS; GENETIC TRANSCRIPTION; HOST CELL; MOLECULE; NONHUMAN; PATHOGENESIS; PATHOGENICITY ISLAND; PROTEIN ASSEMBLY; SALMONELLA; STRUCTURE ACTIVITY RELATION; TYPE III SECRETION SYSTEM; BACTERIAL SECRETION SYSTEM; BIOLOGICAL MODEL; DRUG DELIVERY SYSTEM; PHYSIOLOGY;

BACTERIA (MICROORGANISMS); EUKARYOTA; NEGIBACTERIA;

ANTI-BACTERIAL AGENTS; BACTERIAL SECRETION SYSTEMS; DRUG DELIVERY SYSTEMS; DRUG DESIGN; MODELS, BIOLOGICAL;

EID: 84918818955     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/cbdd.12422     Document Type: Article

References (133)

1. CDC (2013) Antibiotic resistance threats in the United States.
2. Allen H.K., Donato J., Wang H.H., Cloud-Hansen K.A., Davies J., Handelsman J., (2010) Call of the wild: antibiotic resistance genes in natural environments. Nat Rev Microbiol; 8: 251-259.
3. Wellington E.M., Boxall A.B., Cross P., Feil E.J., Gaze W.H., Hawkey P.M., Johnson-Rollings A.S., Jones D.L., Lee N.M., Otten W., Thomas C.M., Williams A.P., (2013) The role of the natural environment in the emergence of antibiotic resistance in Gram-negative bacteria. Lancet Infect Dis; 13: 155-165.
4. Davies J., Davies D., (2010) Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev; 74: 417.
5. Gilbert D.N., Guidos R.J., Boucher H.W., Talbot G.H., Spellberg B., Edwards J.E., Scheld W.M., Bradley J.S., Bartlett J.G., (2010) The 10 x '20 initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin Infect Dis; 50: 1081-1083.
6. Payne D.J., Gwynn M.N., Holmes D.J., Pompliano D.L., (2007) Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov; 6: 29-40.
7. Butler M.S., Blaskovich M.A., Cooper M.A., (2013) Antibiotics in the clinical pipeline in 2013. J Antibiot (Tokyo); 66: 571-591.
8. Schaberle T.F., Hack I.M., (2014) Overcoming the current deadlock in antibiotic research. Trends Microbiol; 22: 165-167.
9. Bassetti M., Merelli M., Temperoni C., Astilean A., (2013) New antibiotics for bad bugs: where are we? Ann Clin Microbiol Antimicrob; 12: 22-37.
10. Lee J.H., Jeong S.H., Cha S.S., Lee S.H., (2007) A lack of drugs for antibiotic-resistant gram-negative bacteria. Nat Rev Drug Discovery; 6: 938-939.
11. Coates A.R.M., Halls G., Hu Y.M., (2011) Novel classes of antibiotics or more of the same? Br J Pharmacol; 163: 184-194.
12. Projan S.J., (2003) Why is big Pharma getting out of antibacterial drug discovery? Curr Opin Microbiol; 6: 427-430.
13. Baron C., (2010) Antivirulence drugs to target bacterial secretion systems. Curr Opin Microbiol; 13: 100-105.
14. Keyser P., Elofsson M., Rosell S., Wolf-Watz H., (2008) Virulence blockers as alternatives to antibiotics: type III secretion inhibitors against Gram-negative bacteria. J Intern Med; 264: 17-29.
15. Allen R.C., Popat R., Diggle S.P., Brown S.P., (2014) Targeting virulence: can we make evolution-proof drugs? Nat Rev Microbiol; 12: 300-308.
16. Clatworthy A.E., Pierson E., Hung D.T., (2007) Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol; 3: 541-548.
17. Duncan M.C., Linington R.G., Auerbuch V., (2012) Chemical inhibitors of the type three secretion system: disarming bacterial pathogens. Antimicrob Agents Chemother; 56: 5433-5441.
18. Cornelis G.R., (2006) The type III secretion injectisome. Nat Rev Microbiol; 4: 811-825.
19. Kubori T., Matsushima Y., Nakamura D., Uralil J., Lara-Tejero M., Sukhan A., Galan J.E., Aizawa S., (1998) Supramolecular structure of the Salmonella typhimurium type III protein secretion system. Science; 280: 602-605.
20. Chatterjee S., Chaudhury S., McShan A.C., Kaur K., De Guzman R.N., (2013) Structure and biophysics of type III secretion in bacteria. Biochemistry; 52: 2508-2517.
21. Izore T., Job V., Dessen A., (2011) Biogenesis, regulation, and targeting of the type III secretion system. Structure; 19: 603-612.
22. Abrusci P., McDowell M.A., Lea S.M., Johnson S., (2014) Building a secreting nanomachine: a structural overview of the T3SS. Curr Opin Struct Biol; 25C: 111-117.
23. Dean P., (2011) Functional domains and motifs of bacterial type III effector proteins and their roles in infection. FEMS Microbiol Rev; 35: 1100-1125.
24. Rosqvist R., Hakansson S., Forsberg A., Wolf-Watz H., (1995) Functional conservation of the secretion and translocation machinery for virulence proteins of yersiniae, salmonellae and shigellae. EMBO J; 14: 4187-4195.
25. Hermant D., Menard R., Arricau N., Parsot C., Popoff M.Y., (1995) Functional conservation of the salmonella and shigella effectors of entry into epithelial-cells. Mol Microbiol; 17: 781-789.
26. Demers J.P., Sgourakis N.G., Gupta R., Loquet A., Giller K., Riedel D., Laube B., Kolbe M., Baker D., Becker S., Lange A., (2013) The common structural architecture of Shigella flexneri and Salmonella typhimurium type three secretion needles. PLoS Pathog; 9: e1003245-e1003256.
27. Spreter T., Yip C.K., Sanowar S., Andre I., Kimbrough T.G., Vuckovic M., Pfuetzner R.A., Deng W.Y., Yu A.C., Finlay B.B., Baker D., Miller S.I., Strynadka N.C.J., (2009) A conserved structural motif mediates formation of the periplasmic rings in the type III secretion system. Nat Struct Mol Biol; 16: 468-476.
28. Abrusci P., Vergara-Irigaray M., Johnson S., Beeby M.D., Hendrixson D.R., Roversi P., Friede M.E., Deane J.E., Jensen G.J., Tang C.M., Lea S.M., (2013) Architecture of the major component of the type III secretion system export apparatus. Nat Struct Mol Biol; 20: 99-104.
29. Zarivach R., Vuckovic M., Deng W.Y., Finlay B.B., Strynadka N.C.J., (2007) Structural analysis of a prototypical ATPase from the type III secretion system. Nat Struct Mol Biol; 14: 131-137.
30. Veenendaal A.K.J., Hodgkinson J.L., Schwarzer L., Stabat D., Zenk S.F., Blocker A.J., (2007) The type III secretion system needle tip complex mediates host cell sensing and translocon insertion. Mol Microbiol; 63: 1719-1730.
31. Mattei P.J., Faudry E., Job V., Izore T., Attree I., Dessen A., (2011) Membrane targeting and pore formation by the type III secretion system translocon. FEBS J; 278: 414-426.
32. Deeds E.J., Bachman J.A., Fontana W., (2012) Optimizing ring assembly reveals the strength of weak interactions. Proc Natl Acad Sci USA; 109: 2348-2353.
33. Galan J.E., Curtiss R., (1989) Cloning and molecular characterization of genes whose products allow salmonella typhimurium to penetrate tissue-culture cells. Proc Natl Acad Sci USA; 86: 6383-6387.
34. Egan F., Barret M., O'Gara F., (2014) The SPI-1-like Type III secretion system: more roles than you think. Frontiers in Plant Science; 5: 34-41.
35. Figueira R., Holden D.W., (2012) Functions of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system effectors. Microbiology-Sgm; 158: 1147-1161.
36. Barret M., Egan F., O'Gara F., (2013) Distribution and diversity of bacterial secretion systems across metagenomic datasets. Environ Microbiol Rep; 5: 117-126.
37. Galan J.E., (2007) SnapShot: effector proteins of type III secretion systems. Cell; 130: 192 -e1.
38. Zhou D.G., Galan J., (2001) Salmonella entry into host cells: the work in concert of type III secreted effector proteins. Microbes Infect; 3: 1293-1298.
39. Figueira R., Watson K.G., Holden D.W., Helaine S., (2013) Identification of salmonella pathogenicity island-2 type III secretion system effectors involved in intramacrophage replication of S. enterica serovar typhimurium: implications for rational vaccine design. Mbio; 4: e00065-13.
40. Kidwai A.S., Mushamiri I., Niemann G.S., Brown R.N., Adkins J.N., Heffron F., (2013) Diverse secreted effectors are required for salmonella persistence in a mouse infection model. PLoS ONE; 8: e70753-e70763.
41. Coburn B., Sekirov I., Finlay B.B., (2007) Type III secretion systems and disease. Clin Microbiol Rev; 20: 535.
42. Akeda Y., Galan J.E., (2005) Chaperone release and unfolding of substrates in type III secretion. Nature; 437: 911-915.
43. Lee S.H., Galan J.E., (2004) Salmonella type III secretion-associated chaperones confer secretion-pathway specificity. Mol Microbiol; 51: 483-495.
44. Boyd A.P., Lambermont I., Cornelis G.R., (2000) Competition between the Yops of Yersinia enterocolitica for delivery into eukaryotic cells: role of the SycE chaperone binding domain of YopE. J Bacteriol; 182: 4811-4821.
45. Ellermeier J.R., Slauch J.M., (2007) Adaptation to the host environment: regulation of the SPI1 type III secretion system in Salmonella enterica serovar Typhimurium. Curr Opin Microbiol; 10: 24-29.
46. Osborne S.E., Coombes B.K., (2011) Transcriptional priming of salmonella pathogenicity island-2 precedes cellular invasion. PLoS ONE; 6: e21648-e21656.
47. Yahr T.L., Wolfgang M.C., (2006) Transcriptional regulation of the Pseudomonas aeruginosa type III secretion system. Mol Microbiol; 62: 631-640.
48. Li L., Yan H., Feng L., Li Y., Lu P., Hu Y., Chen S., (2014) LcrQ blocks the role of LcrF in regulating the Ysc-Yop Type III secretion genes in Yersinia pseudotuberculosis. PLoS ONE; 9: e92243-e92254.
49. Dorman C.J., Porter M.E., (1998) The Shigella virulence gene regulatory cascade: a paradigm of bacterial gene control mechanisms. Mol Microbiol; 29: 677-684.
50. Sukhan A., Kubori T., Wilson J., Galan J.E., (2001) Genetic analysis of assembly of the Salmonella enterica serovar typhimurium type III secretion-associated needle complex. J Bacteriol; 183: 1159-1167.
51. Kauppi A.M., Nordfelth R., Uvell H., Wolf-Watz H., Elofsson M., (2003) Targeting bacterial virulence: inhibitors of type III secretion in Yersinia. Chem Biol; 10: 241-249.
52. Nordfelth R., Kauppi A.M., Norberg H.A., Wolf-Watz H., Elofsson M., (2005) Small-molecule inhibitors specifically targeting type III secretion. Infect Immun; 73: 3104-3114.
53. Kauppi A.M., Andersson C.D., Norberg H.A., Sundin C., Linusson A., Elofsson M., (2007) Inhibitors of type III secretion in Yersinia: design, synthesis and multivariate QSAR of 2-arylsulfonylamino-benzanilides. Bioorg Med Chem; 15: 6994-7011.
54. Muschiol S., Normark S., Henriques-Normark B., Subtil A., (2009) Small molecule inhibitors of the Yersinia type III secretion system impair the development of Chlamydia after entry into host cells. BMC Microbiol; 9: 75-82.
55. Slepenkin A., Chu H., Elofsson M., Keyser P., Peterson E.M., (2011) Protection of Mice From a Chlamydia trachomatis Vaginal Infection Using a Salicylidene Acylhydrazide, a Potential Microbicide. J Infect Dis; 204: 1313-1320.
56. Bailey L., Gylfe A., Sundin C., Muschiol S., Elofsson M., Nordstrom P., Henriques-Normark B., Lugert R., Waldenstrom A., Wolf-Watz H., Bergstrom S., (2007) Small molecule inhibitors of type III secretion in Yersinia block the Chlamydia pneumoniae infection cycle. FEBS Lett; 581: 587-595.
57. Muschiol S., Bailey L., Gylfe A., Sundin C., Hultenby K., Bergstrom S., Elofsson M., Wolf-Watz H., Normark S., Henriques-Normark B., (2006) A small-molecule inhibitor of type III secretion inhibits different stages of the infectious cycle of Chlamydia trachomatis. Proc Natl Acad Sci USA; 103: 14566-14571.
58. Veenendaal A.K.J., Sundin C., Blocker A.J., (2009) Small-molecule type III secretion system inhibitors block assembly of the shigella type III secreton. J Bacteriol; 191: 563-570.
59. Martinez-Argudo I., Veenendaal A.K., Liu X., Roehrich A.D., Ronessen M.C., Franzoni G., van Rietschoten K.N., Morimoto Y.V., Saijo-Hamano Y., Avison M.B., Studholme D.J., Namba K., Minamino T., Blocker A.J., (2013) Isolation of salmonella mutants resistant to the inhibitory effect of salicylidene acylhydrazides on flagella-mediated motility. PLoS ONE; 8: e52179.
60. Negrea A., Bjur E., Ygberg S.E., Elofsson M., Wolf-Watz H., Rhen M., (2007) Salicylidene acylhydrazides that affect type III protein secretion in Salmonella enterica serovar Typhimurium. Antimicrob Agents Chemother; 51: 2867-2876.
61. Hudson D.L., Layton A.N., Field T.R., Bowen A.J., Wolf-Watz H., Elofsson M., Stevens M.P., Galyov E.E., (2007) Inhibition of type III secretion in Salmonella enterica serovar typhimurium by small-molecule inhibitors. Antimicrob Agents Chemother; 51: 2631-2635.
62. Puiac S., Sem X.H., Negrea A., Rhen M., (2011) Small-molecular virulence inhibitors show divergent and immunomodulatory effects in infection models of Salmonella enterica serovar Typhimurium. Int J Antimicrob Agents; 38: 409-416.
63. Layton A.N., Hudson D.L., Thompson A., Hinton J.C., Stevens J.M., Galyov E.E., Stevens M.P., (2010) Salicylidene acylhydrazide-mediated inhibition of type III secretion system-1 in Salmonella enterica serovar Typhimurium is associated with iron restriction and can be reversed by free iron. FEMS Microbiol Lett; 302: 114-122.
64. Gauthier A., Robertson M.L., Lowden M., Ibarra J.A., Puente J.L., Finlay B.B., (2005) Transcriptional inhibitor of virulence factors in enteropathogenic Escherichia coli. Antimicrob Agents Chemother; 49: 4101-4109.
65. Tree J.J., Wang D., McInally C., Mahajan A., Layton A., Houghton I., Elofsson M., Stevens M.P., Gally D.L., Roe A.J., (2009) Characterization of the effects of salicylidene acylhydrazide compounds on type III secretion in Escherichia coli O157:H7. Infect Immun; 77: 4209-4220.
66. Wang D., Zetterstrom C.E., Gabrielsen M., Beckham K.S.H., Tree J.J., Macdonald S.E., Byron O., et al,. (2011) Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds. J Biol Chem; 286: 29922-29931.
67. Gabrielsen M., Beckham K.S., Feher V.A., Zetterstrom C.E., Wang D., Muller S., Elofsson M., Amaro R.E., Byron O., Roe A.J., (2012) Structural characterisation of Tpx from Yersinia pseudotuberculosis reveals insights into the binding of salicylidene acylhydrazide compounds. PLoS ONE; 7: e32217.
68. Slepenkin A., Enquist P.A., Hagglund U., de la Maza L.M., Elofsson M., Peterson E.M., (2007) Reversal of the antichlamydial activity of putative type III secretion inhibitors by iron. Infect Immun; 75: 3478-3489.
69. Engstrom P., Nguyen B.D., Normark J., Nilsson I., Bastidas R.J., Gylfe A., Elofsson M., Fields K.A., Valdivia R.H., Wolf-Watz H., Bergstrom S., (2013) Mutations in hemG mediate resistance to salicylidene acylhydrazides, demonstrating a novel link between protoporphyrinogen oxidase (HemG) and Chlamydia trachomatis infectivity. J Bacteriol; 195: 4221-4230.
70. Rzhepishevska O., Hakobyan S., Ekstrand-Hammarstrom B., Nygren Y., Karlsson T., Bucht A., Elofsson M., Boily J.F., Ramstedt M., (2014) The gallium(III)-salicylidene acylhydrazide complex shows synergistic anti-biofilm effect and inhibits toxin production by Pseudomonas aeruginosa. J Inorg Biochem; 138C: 1-8.
71. Felise H.B., Nguyen H.V., Pfuetzner R.A., Barry K.C., Jackson S.R., Blanc M.P., Bronstein P.A., Kline T., Miller S.I., (2008) An inhibitor of gram-negative bacterial virulence protein secretion. Cell Host Microbe; 4: 325-336.
72. Kline T., Barry K.C., Jackson S.R., Felise H.B., Nguyen H.V., Miller S.I., (2009) Tethered thiazolidinone dimers as inhibitors of the bacterial type III secretion system. Bioorg Med Chem Lett; 19: 1340-1343.
73. Jessen D.L., Bradley D.S., Nilles M.L., (2014) A type III secretion system inhibitor targets YopD while revealing differential regulation of secretion in calcium-blind mutants of Yersinia pestis. Antimicrob Agents Chemother; 58: 839-850.
74. Aiello D., Williams J.D., Majgier-Baranowska H., Patel I., Peet N.P., Huang J., Lory S., Bowlin T.L., Moir D.T., (2010) Discovery and characterization of inhibitors of Pseudomonas aeruginosa type III secretion. Antimicrob Agents Chemother; 54: 1988-1999.
75. Bowlin N.O., Williams J.D., Knoten C.A., Torhan M.C., Tashjian T.F., Li B., Aiello D., Mecsas J., Hauser A.R., Peet N.P., Bowlin T.L., Moir D.T., (2014) Mutations in the Pseudomonas aeruginosa needle protein gene pscF confer resistance to phenoxyacetamide inhibitors of the type III secretion system. Antimicrob Agents Chemother; 58: 2211-2220.
76. 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., Alekshun M.N., (2009) N-hydroxybenzimidazole inhibitors of the transcription factor LcrF in Yersinia: novel antivirulence agents. J Med Chem; 52: 5626-5634.
77. 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., 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.
78. 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., Kim O.K., (2010) N-Hydroxybenzimidazole inhibitors of ExsA MAR transcription factor in Pseudomonas aeruginosa: In vitro anti-virulence activity and metabolic stability. Bioorg Med Chem Lett; 20: 3380-3383.
79. Koppolu V., Osaka I., Skredenske J.M., Kettle B., Hefty P.S., Li J.Q., Egan S.M., (2013) Small-molecule inhibitor of the shigella flexneri master virulence regulator VirF. Infect Immun; 81: 4220-4231.
80. Swietnicki W., Carmany D., Retford M., Guelta M., Dorsey R., Bozue J., Lee M.S., Olson M.A., (2011) Identification of small-molecule inhibitors of yersinia pestis type III secretion system YscN ATPase. PLoS ONE; 6: e19716-e19729.
81. Puiac S., Negrea A., Richter-Dahlfors A., Plant L., Rhen M., (2009) Omeprazole antagonizes virulence and inflammation in Salmonella enterica-infected RAW264.7 cells. Antimicrob Agents Chemother; 53: 2402-2409.
82. Lee V.T., Pukatzki S., Sato H., Kikawada E., Kazimirova A.A., Huang J., Li X.H., Arm J.P., Frank D.W., Lory S., (2007) Pseudolipasin A is a specific inhibitor for phospholipase A(2) activity of Pseudomonas aeruginosa cytotoxin ExoU. Infect Immun; 75: 1089-1098.
83. Harmon D.E., Davis A.J., Castillo C., Mecsas J., (2010) Identification and characterization of small-molecule inhibitors of Yop translocation in Yersinia pseudotuberculosis. Antimicrob Agents Chemother; 54: 3241-3254.
84. Kimura K., Iwatsuki M., Nagai T., Matsumoto A., Takahashi Y., Shiomi K., Omura S., Abe A., (2011) A small-molecule inhibitor of the bacterial type III secretion system protects against in vivo infection with Citrobacter rodentium. J Antibiot (Tokyo); 64: 197-203.
85. Iwatsuki M., Uchida R., Yoshijima H., Ui H., Shiomi K., Kim Y.P., Hirose T., Sunazuka T., Abe A., Tomoda H., Omura S., (2008) Guadinomines, Type III secretion system inhibitors, produced by streptomyces sp K01-0509. J Antibiot; 61: 230-236.
86. Li J.F., Lv C., Sun W.Y., Li Z.Y., Han X.W., Li Y.Y., Shen Y.M., (2013) Cytosporone B, an inhibitor of the type III secretion system of Salmonella enterica serovar typhimurium. Antimicrob Agents Chemother; 57: 2191-2198.
87. Vikram A., Jayaprakasha G.K., Jesudhasan P.R., Pillai S.D., Patil B.S., (2010) Suppression of bacterial cell-cell signalling, biofilm formation and type III secretion system by citrus flavonoids. J Appl Microbiol; 109: 515-527.
88. Kauppi A.M., Nordfelth R., Hagglund U., Wolf-Watz H., Elofsson M., (2003) Salicylanilides are potent inhibitors of type III secretion in Yersinia. Adv Exp Med Biol; 529: 97-100.
89. Ohgita T., Hayashi N., Hama S., Tsuchiya H., Gotoh N., Kogure K., (2013) A novel effector secretion mechanism based on proton-motive force-dependent type III secretion apparatus rotation. FASEB J; 27: 2862-2872.
90. Ohgita T., Hayashi N., Gotoh N., Kogure K., (2013) Suppression of type III effector secretion by polymers. Open Biol; 3: 130133.
91. Strickley R.G., (2004) Solubilizing excipients in oral and injectable formulations. Pharm Res; 21: 201-230.
92. Ochoa T.J., Clearly T.G., (2004) Lactoferrin disruption of bacterial type III secretion systems. Biometals; 17: 257-260.
93. Ochoa T.J., Noguera-Obenza M., Ebel F., Guzman C.A., Gomez H.F., Cleary T.G., (2003) Lactoferrin impairs type III secretory system function in enteropathogenic Escherichia coli. Infect Immun; 71: 5149-5155.
94. Gomez H.F., Ochoa T.J., Carlin L.G., Cleary T.G., (2003) Human lactoferrin impairs virulence of Shigella flexneri. J Infect Dis; 187: 87-95.
95. Mosquito S., Ochoa T.J., Cok J., Cleary T.G., (2010) Effect of bovine lactoferrin in Salmonella ser. Typhimurium infection in mice. Biometals; 23: 515-521.
96. Yekta M.A., Verdonck F., Van Den Broeck W., Goddeeris B.M., Cox E., Vanrompay D., (2010) Lactoferrin inhibits E. coli O157:H7 growth and attachment to intestinal epithelial cells. Vet Med; 55: 359-368.
97. Ochoa T.J., Cleary T.G., (2009) Effect of lactoferrin on enteric pathogens. Biochimie; 91: 30-34.
98. Stone C.B., Bulir D.C., Emdin C.A., Pirie R.M., Porfilio E.A., Slootstra J.W., Mahony J.B., (2011) Chlamydia Pneumoniae CdsL Regulates CdsN ATPase Activity, and Disruption with a Peptide Mimetic Prevents Bacterial Invasion. Front Microbiol; 2: 21.
99. Hayward R.D., Hume P.J., McGhie E.J., Koronakis V., (2002) A Salmonella SipB-derived polypeptide blocks the 'trigger' mechanism of bacterial entry into eukaryotic cells. Mol Microbiol; 45: 1715-1727.
100. Larzabal M., Mercado E.C., Vilte D.A., Salazar-Gonzalez H., Cataldi A., Navarro-Garcia F., (2010) Designed coiled-coil peptides inhibit the type three secretion system of enteropathogenic Escherichia coli. PLoS ONE; 5: e9046.
101. Olive A.J., Kenjale R., Espina M., Moore D.S., Picking W.L., Picking W.D., (2007) Bile salts stimulate recruitment of IpaB to the Shigella flexneli surface, where it colocalizes with IpaD at the tip of the type III secretion needle. Infect Immun; 75: 2626-2629.
102. Pope L.M., Reed K.E., Payne S.M., (1995) Increased protein secretion and adherence to HeLa cells by Shigella spp. following growth in the presence of bile salts. Infect Immun; 63: 3642-3648.
103. Prouty A.M., Gunn J.S., (2000) Salmonella enterica serovar typhimurium invasion is repressed in the presence of bile. Infect Immun; 68: 6763-6769.
104. Wang Y., Nordhues B.A., Zhong D., De Guzman R.N., (2010) NMR characterization of the interaction of the Salmonella type III secretion system protein SipD and bile salts. Biochemistry; 49: 4220-4226.
105. Dickenson N.E., Zhang L., Epler C.R., Adam P.R., Picking W.L., Picking W.D., (2011) Conformational changes in IpaD from Shigella flexneri upon binding bile salts provide insight into the second step of type III secretion. Biochemistry; 50: 172-180.
106. Chatterjee S., Zhong D., Nordhues B.A., Battaile K.P., Lovell S., De Guzman R.N., (2011) The crystal structures of the Salmonella type III secretion system tip protein SipD in complex with deoxycholate and chenodeoxycholate. Protein Sci; 20: 75-86.
107. Barta M.L., Guragain M., Adam P., Dickenson N.E., Patil M., Geisbrecht B.V., Picking W.L., Picking W.D., (2012) Identification of the bile salt binding site on IpaD from Shigella flexneri and the influence of ligand binding on IpaD structure. Proteins; 80: 935-945.
108. Lafont F., Tran Van Nhieu G., Hanada K., Sansonetti P., van der Goot F.G., (2002) Initial steps of Shigella infection depend on the cholesterol/sphingolipid raft-mediated CD44-IpaB interaction. EMBO J; 21: 4449-4457.
109. Epler C.R., Dickenson N.E., Olive A.J., Picking W.L., Picking W.D., (2009) Liposomes Recruit IpaC to the Shigella flexneri Type III Secretion Apparatus Needle as a Final Step in Secretion Induction. Infect Immun; 77: 2754-2761.
110. Mounier J., Boncompain G., Senerovic L., Lagache T., Chretien F., Perez F., Kolbe M., Olivo-Marin J.C., Sansonetti P.J., Sauvonnet N., (2012) Shigella effector IpaB-induced cholesterol relocation disrupts the Golgi complex and recycling network to inhibit host cell secretion. Cell Host Microbe; 12: 381-389.
111. Hayward R.D., Cain R.J., McGhie E.J., Phillips N., Garner M.J., Koronakis V., (2005) Cholesterol binding by the bacterial type III translocon is essential for virulence effector delivery into mammalian cells. Mol Microbiol; 56: 590-603.
112. Schoehn G., Di Guilmi A.M., Lemaire D., Attree I., Weissenhorn W., Dessen A., (2003) Oligomerization of type III secretion proteins PopB and PopD precedes pore formation in Pseudomonas. EMBO J; 22: 4957-4967.
113. Kayath C.A., 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.
114. Nawabi P., Catron D.M., Haldar K., (2008) Esterification of cholesterol by a type III secretion effector during intracellular Salmonella infection. Mol Microbiol; 68: 173-185.
115. Dickenson N.E., Arizmendi O., Patil M.K., Toth R.T.t., Middaugh C.R., Picking W.D., Picking W.L., (2013) N-Terminus of IpaB Provides a Potential Anchor to the Shigella Type III Secretion System Tip Complex Protein IpaD. Biochemistry; 52: 8790-8799.
116. Rathinavelan T., Tang C., De Guzman R.N., (2011) Characterization of the Interaction between the Salmonella Type III Secretion System Tip Protein SipD and the Needle Protein PrgI by Paramagnetic Relaxation Enhancement. J Biol Chem; 286: 4922-4930.
117. Andricopulo A.D., Montanari C.A., (2005) Structure-activity relationships for the design of small-molecule inhibitors. Mini Rev Med Chem; 5: 585-593.
118. Dahlgren M.K., Zetterstrom C.E., Gylfe S., Linusson A., Elofsson M., (2010) Statistical molecular design of a focused salicylidene acylhydrazide library and multivariate QSAR of inhibition of type III secretion in the Gram-negative bacterium Yersinia. Bioorg Med Chem; 18: 2686-2703.
119. Enquist P.A., Gylfe A., Hagglund U., Lindstom P., Norberg-Scherman H., Sundin C., Elofsson M., (2012) Derivatives of 8-hydroxyquinoline-antibacterial agents that target intra- and extracellular Gram-negative pathogens. Bioorg Med Chem Lett; 22: 3550-3553.
120. Ur-Rehman T., Slepenkin A., Chu H., Blomgren A., Dahlgren M.K., Zetterstrom C.E., Peterson E.M., Elofsson M., Gylfe A., (2012) Pre-clinical pharmacokinetics and anti-chlamydial activity of salicylidene acylhydrazide inhibitors of bacterial type III secretion. J Antibiot (Tokyo); 65: 397-404.
121. Ur-Rehman T., Nordfelth R., Blomgren A., Zetterstrom C.E., Elofsson M., Gylfe A., (2012) Preliminary pharmacokinetics of the bacterial virulence inhibitor N '-(3,5-Dibromo-2-Hydroxy-Benzylidenene)-Nicotinic acid hydrazide. Adv Yersinia Res; 954: 349-356.
122. Hughes J.P., Rees S., Kalindjian S.B., Philpott K.L., (2011) Principles of early drug discovery. Br J Pharmacol; 162: 1239-1249.
123. Zetterstrom C.E., Hasselgren J., Salin O., Davis R.A., Quinn R.J., Sundin C., Elofsson M., (2013) The resveratrol tetramer (-)-hopeaphenol inhibits type III secretion in the gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa. PLoS ONE; 8: e81969.
124. Kline T., Felise H.B., Barry K.C., Jackson S.R., Nguyen H.V., Miller S.I., (2008) Substituted 2-Imino-5-arylidenethiazolidin-4-one Inhibitors of Bacterial Type III Secretion. J Med Chem; 51: 7065-7074.
125. Linington R.G., Robertson M., Gauthier A., Finlay B.B., van Soes R., Andersen R.J., (2002) Caminoside A, an antimicrobial glycolipid isolated from the marine sponge Caminus sphaeroconia. Org Lett; 4: 4089-4092.
126. Linington R.G., Robertson M., Gauthier A., Finlay B.B., MacMillan J.B., Molinski T.F., van Soest R., Andersen R.J., (2006) Caminosides B-D, antimicrobial glycolipids isolated from the marine sponge Caminus sphaeroconia. J Nat Prod; 69: 173-177.
127. Duncan M.C., Wong W.R., Dupzyk A.J., Bray W.M., Linington R.G., Auerbuch V., (2014) An NF-kappa B-based high-throughput screen identifies piericidins as inhibitors of the Yersinia pseudotuberculosis type III secretion system. Antimicrob Agents Chemother; 58: 1118-1126.
128. Yin S., Davis R.A., Shelper T., Sykes M.L., Avery V.M., Elofsson M., Sundin C., Quinn R.J., (2011) Pseudoceramines A-D, new antibacterial bromotyrosine alkaloids from the marine sponge Pseudoceratina sp. Org Biomol Chem; 9: 6755-6760.
129. Dahlgren M.K., Kauppi A.M., Olsson I.M., Linusson A., Elofsson M., (2007) Design, synthesis, and multivariate quantitative structure-activity relationship of salicylanilides-potent inhibitors of type III secretion in Yersinia. J Med Chem; 50: 6177-6188.
130. Wolf K., Betts H.J., Chellas-Gery B., Hower S., Linton C.N., Fields K.A., (2006) Treatment of Chlamydia trachomatis with a small molecule inhibitor of the Yersinia type III secretion system disrupts progression of the chlamydial developmental cycle. Mol Microbiol; 61: 1543-1555.
131. Zigangirova N.A., Zayakin E.S., Kapotina L.N., Kost E.A., Didenko L.V., Davydova D.Y., Rumyanceva J.P., Gintsburg A.L., (2012) Development of chlamydial type III secretion system inhibitors for suppression of acute and chronic forms of chlamydial infection. Acta Naturae; 4: 87-97.
132. Pan N., Lee C., Goguen J., (2007) High throughput screening for small-molecule inhibitors of type III secretion in Yersinia pestis. Genus Yersinia: From Genomics to Function; 603: 367-375.
133. Pan N.J., Brady M.J., Leong J.M., Goguen J.D., (2009) Targeting type III secretion in Yersinia pestis. Antimicrob Agents Chemother; 53: 385-392.