Advertisement

Strategies to Block Bacterial Pathogenesis by Interference with Motility and Chemotaxis

  • Marc ErhardtEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 398)

Abstract

Infections by motile, pathogenic bacteria, such as Campylobacter species, Clostridium species, Escherichia coli, Helicobacter pylori, Listeria monocytogenes, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Salmonella species, Vibrio cholerae, and Yersinia species, represent a severe economic and health problem worldwide. Of special importance in this context is the increasing emergence and spread of multidrug-resistant bacteria. Due to the shortage of effective antibiotics for the treatment of infections caused by multidrug-resistant, pathogenic bacteria, the targeting of novel, virulence-relevant factors constitutes a promising, alternative approach. Bacteria have evolved distinct motility structures for movement across surfaces and in aqueous environments. In this review, I will focus on the bacterial flagellum, the associated chemosensory system, and the type-IV pilus as motility devices, which are crucial for bacterial pathogens to reach a preferred site of infection, facilitate biofilm formation, and adhere to surfaces or host cells. Thus, those nanomachines constitute potential targets for the development of novel anti-infectives that are urgently needed at a time of spreading antibiotic resistance. Both bacterial flagella and type-IV pili (T4P) are intricate macromolecular complexes made of dozens of different proteins and their motility function relies on the correct spatial and temporal assembly of various substructures. Specific type-III and type-IV secretion systems power the export of substrate proteins of the bacterial flagellum and type-IV pilus, respectively, and are homologous to virulence-associated type-III and type-II secretion systems. Accordingly, bacterial flagella and T4P represent attractive targets for novel antivirulence drugs interfering with synthesis, assembly, and function of these motility structures.

Keywords

Motility Structure Bacterial Motility Chemosensory System Flagellar Motor Bacterial Flagellum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Marc Erhardt is supported by the Helmholtz Association Young Investigator grant VH-NG-932 and the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (grant 334030).

References

  1. Abby SS, Rocha EP (2012) The non-flagellar type III secretion system evolved from the bacterial flagellum and diversified into host-cell adapted systems. PLoS Genet 8(9):e1002983. doi: 10.1371/journal.pgen.1002983 PubMedPubMedCentralCrossRefGoogle Scholar
  2. Abrusci P, Vergara-Irigaray M, Johnson S, Beeby MD, Hendrixson DR, Roversi P, Friede ME, Deane JE, Jensen GJ, Tang CM, Lea SM (2013) Architecture of the major component of the type III secretion system export apparatus. Nat Struct Mol Biol 20(1):99–104. doi: 10.1038/nsmb.2452 PubMedCrossRefGoogle Scholar
  3. Aizawa SI (1996) Flagellar assembly in Salmonella typhimurium. Mol Microbiol 19(1):1–5PubMedCrossRefGoogle Scholar
  4. Akeda Y, Galan JE (2005) Chaperone release and unfolding of substrates in type III secretion. Nature 437(7060):911–915. doi: 10.1038/nature03992 PubMedCrossRefGoogle Scholar
  5. Allen-Vercoe E, Woodward MJ (1999) The role of flagella, but not fimbriae, in the adherence of Salmonella enterica serotype Enteritidis to chick gut explant. J Med Microbiol 48(8):771–780PubMedCrossRefGoogle Scholar
  6. Andersen-Nissen E, Smith KD, Strobe KL, Barrett SL, Cookson BT, Logan SM, Aderem A (2005) Evasion of Toll-like receptor 5 by flagellated bacteria. Proc Natl Acad Sci USA 102(26):9247–9252. doi: 10.1073/pnas.0502040102 PubMedPubMedCentralCrossRefGoogle Scholar
  7. Arora SK, Neely AN, Blair B, Lory S, Ramphal R (2005) Role of motility and flagellin glycosylation in the pathogenesis of Pseudomonas aeruginosa burn wound infections. Infect Immun 73(7):4395–4398. doi: 10.1128/IAI.73.7.4395-4398.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  8. Berg HC, Anderson RA (1973) Bacteria swim by rotating their flagellar filaments. Nature 245(5425):380–382PubMedCrossRefGoogle Scholar
  9. Black RE, Levine MM, Clements ML, Hughes TP, Blaser MJ (1988) Experimental Campylobacter jejuni infection in humans. J Infect Dis 157(3):472–479PubMedCrossRefGoogle Scholar
  10. Blair DF, Berg HC (1990) The MotA protein of E. coli is a proton-conducting component of the flagellar motor. Cell 60(3):439–449PubMedCrossRefGoogle Scholar
  11. Brown DA, Berg HC (1974) Temporal stimulation of chemotaxis in Escherichia coli. Proc Natl Acad Sci USA 71(4):1388–1392PubMedPubMedCentralCrossRefGoogle Scholar
  12. Burrows LL (2005) Weapons of mass retraction. Mol Microbiol 57(4):878–888. doi: 10.1111/j.1365-2958.2005.04703.x PubMedCrossRefGoogle Scholar
  13. Chadsey MS, Karlinsey JE, Hughes KT (1998) The flagellar anti-sigma factor FlgM actively dissociates Salmonella typhimurium sigma28 RNA polymerase holoenzyme. Genes Dev 12(19):3123–3136PubMedPubMedCentralCrossRefGoogle Scholar
  14. Chevance FF, Hughes KT (2008) Coordinating assembly of a bacterial macromolecular machine. Nat Rev Microbiol 6(6):455–465. doi: 10.1038/nrmicro1887 PubMedCrossRefGoogle Scholar
  15. Chun SY, Parkinson JS (1988) Bacterial motility: membrane topology of the Escherichia coli MotB protein. Science 239(4837):276–278PubMedCrossRefGoogle Scholar
  16. Claret L, Calder SR, Higgins M, Hughes C (2003) Oligomerization and activation of the FliI ATPase central to bacterial flagellum assembly. Mol Microbiol 48(5):1349–1355PubMedPubMedCentralCrossRefGoogle Scholar
  17. Dons L, Eriksson E, Jin Y, Rottenberg ME, Kristensson K, Larsen CN, Bresciani J, Olsen JE (2004) Role of flagellin and the two-component CheA/CheY system of Listeria monocytogenes in host cell invasion and virulence. Infect Immun 72(6):3237–3244. doi: 10.1128/IAI.72.6.3237-3244.2004 PubMedPubMedCentralCrossRefGoogle Scholar
  18. Erhardt M, Dersch P (2015) Regulatory principles governing Salmonella and Yersinia virulence. Front Microbiol 6:949. doi: 10.3389/fmicb.2015.00949 PubMedPubMedCentralCrossRefGoogle Scholar
  19. Erhardt M, Hirano T, Su Y, Paul K, Wee DH, Mizuno S, Aizawa S, Hughes KT (2010) The role of the FliK molecular ruler in hook-length control in Salmonella enterica. Mol Microbiol 75(5):1272–1284. doi: 10.1111/j.1365-2958.2010.07050.x PubMedPubMedCentralCrossRefGoogle Scholar
  20. Erhardt M, Singer HM, Wee DH, Keener JP, Hughes KT (2011) An infrequent molecular ruler controls flagellar hook length in Salmonella enterica. EMBO J 30(14):2948–2961. doi: 10.1038/emboj.2011.185 PubMedPubMedCentralCrossRefGoogle Scholar
  21. Erhardt M, Mertens ME, Fabiani FD, Hughes KT (2014) ATPase-independent type-III protein secretion in Salmonella enterica. PLoS Genet 10(11):e1004800. doi: 10.1371/journal.pgen.1004800 PubMedPubMedCentralCrossRefGoogle Scholar
  22. Felise HB, Nguyen HV, Pfuetzner RA, Barry KC, Jackson SR, Blanc MP, Bronstein PA, Kline T, Miller SI (2008) An inhibitor of gram-negative bacterial virulence protein secretion. Cell Host Microbe 4(4):325–336. doi: 10.1016/j.chom.2008.08.001 PubMedPubMedCentralCrossRefGoogle Scholar
  23. Fernandez-Lopez R, Machon C, Longshaw CM, Martin S, Molin S, Zechner EL, Espinosa M, Lanka E, de la Cruz F (2005) Unsaturated fatty acids are inhibitors of bacterial conjugation. Microbiology 151(Pt 11):3517–3526. doi: 10.1099/mic.0.28216-0 PubMedCrossRefGoogle Scholar
  24. Ferris HU, Minamino T (2006) Flipping the switch: bringing order to flagellar assembly. Trends Microbiol 14(12):519–526. doi: 10.1016/j.tim.2006.10.006 PubMedCrossRefGoogle Scholar
  25. Finlay BB, Falkow S (1989) Salmonella as an intracellular parasite. Mol Microbiol 3(12):1833–1841PubMedCrossRefGoogle Scholar
  26. Francez-Charlot A, Laugel B, Van Gemert A, Dubarry N, Wiorowski F, Castanie-Cornet MP, Gutierrez C, Cam K (2003) RcsCDB His-Asp phosphorelay system negatively regulates the flhDC operon in Escherichia coli. Mol Microbiol 49(3):823–832PubMedCrossRefGoogle Scholar
  27. Franchi L, Kamada N, Nakamura Y, Burberry A, Kuffa P, Suzuki S, Shaw MH, Kim YG, Nunez G (2012) NLRC4-driven production of IL-1beta discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat Immunol 13(5):449–456. doi: 10.1038/ni.2263 PubMedPubMedCentralCrossRefGoogle Scholar
  28. Francis NR, Irikura VM, Yamaguchi S, DeRosier DJ, Macnab RM (1992) Localization of the Salmonella typhimurium flagellar switch protein FliG to the cytoplasmic M-ring face of the basal body. Proc Natl Acad Sci USA 89(14):6304–6308PubMedPubMedCentralCrossRefGoogle Scholar
  29. Friedlander RS, Vlamakis H, Kim P, Khan M, Kolter R, Aizenberg J (2013) Bacterial flagella explore microscale hummocks and hollows to increase adhesion. Proc Natl Acad Sci USA 110(14):5624–5629. doi: 10.1073/pnas.1219662110 PubMedPubMedCentralCrossRefGoogle Scholar
  30. Fronzes R, Christie PJ, Waksman G (2009) The structural biology of type IV secretion systems. Nat Rev Microbiol 7(10):703–714. doi: 10.1038/nrmicro2218 PubMedCrossRefGoogle Scholar
  31. Garvis S, Munder A, Ball G, de Bentzmann S, Wiehlmann L, Ewbank JJ, Tummler B, Filloux A (2009) Caenorhabditis elegans semi-automated liquid screen reveals a specialized role for the chemotaxis gene cheB2 in Pseudomonas aeruginosa virulence. PLoS Pathog 5(8):e1000540. doi: 10.1371/journal.ppat.1000540 PubMedPubMedCentralCrossRefGoogle Scholar
  32. Gauthier A, Robertson ML, Lowden M, Ibarra JA, Puente JL, Finlay BB (2005) Transcriptional inhibitor of virulence factors in enteropathogenic Escherichia coli. Antimicrob Agents Chemother 49(10):4101–4109. doi: 10.1128/AAC.49.10.4101-4109.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  33. Giron JA, Torres AG, Freer E, Kaper JB (2002) The flagella of enteropathogenic Escherichia coli mediate adherence to epithelial cells. Mol Microbiol 44(2):361–379PubMedCrossRefGoogle Scholar
  34. Gold VA, Salzer R, Averhoff B, Kuhlbrandt W (2015) Structure of a type IV pilus machinery in the open and closed state. eLife 4. doi: 10.7554/eLife.07380
  35. Hahn HP (1997) The type-4 pilus is the major virulence-associated adhesin of Pseudomonas aeruginosa–a review. Gene 192(1):99–108PubMedCrossRefGoogle Scholar
  36. Haiko J, Westerlund-Wikstrom B (2013) The role of the bacterial flagellum in adhesion and virulence. Biology 2(4):1242–1267. doi: 10.3390/biology2041242 PubMedPubMedCentralCrossRefGoogle Scholar
  37. Hara N, Morimoto YV, Kawamoto A, Namba K, Minamino T (2012) Interaction of the extreme N-terminal region of FliH with FlhA is required for efficient bacterial flagellar protein export. J Bacteriol 194(19):5353–5360. doi: 10.1128/JB.01028-12 PubMedPubMedCentralCrossRefGoogle Scholar
  38. Harshey RM (2003) Bacterial motility on a surface: many ways to a common goal. Annu Rev Microbiol 57:249–273. doi: 10.1146/annurev.micro.57.030502.091014 PubMedCrossRefGoogle Scholar
  39. Hazelbauer GL, Falke JJ, Parkinson JS (2008) Bacterial chemoreceptors: high-performance signaling in networked arrays. Trends Biochem Sci 33(1):9–19. doi: 10.1016/j.tibs.2007.09.014 PubMedCrossRefGoogle Scholar
  40. Heroven AK, Sest M, Pisano F, Scheb-Wetzel M, Steinmann R, Bohme K, Klein J, Munch R, Schomburg D, Dersch P (2012) Crp induces switching of the CsrB and CsrC RNAs in Yersinia pseudotuberculosis and links nutritional status to virulence. Front Cell Infect Microbiol 2:158. doi: 10.3389/fcimb.2012.00158 PubMedPubMedCentralCrossRefGoogle Scholar
  41. Hilleringmann M, Pansegrau W, Doyle M, Kaufman S, MacKichan ML, Gianfaldoni C, Ruggiero P, Covacci A (2006) Inhibitors of Helicobacter pylori ATPase Cagalpha block CagA transport and cag virulence. Microbiology 152(Pt 10):2919–2930. doi: 10.1099/mic.0.28984-0 PubMedCrossRefGoogle Scholar
  42. Hughes KT, Gillen KL, Semon MJ, Karlinsey JE (1993) Sensing structural intermediates in bacterial flagellar assembly by export of a negative regulator. Science 262(5137):1277–1280PubMedCrossRefGoogle Scholar
  43. Ibuki T, Uchida Y, Hironaka Y, Namba K, Imada K, Minamino T (2013) Interaction between FliJ and FlhA, components of the bacterial flagellar type III export apparatus. J Bacteriol 195(3):466–473. doi: 10.1128/JB.01711-12 PubMedPubMedCentralCrossRefGoogle Scholar
  44. Imada K, Minamino T, Tahara A, Namba K (2007) Structural similarity between the flagellar type III ATPase FliI and F1-ATPase subunits. Proc Natl Acad Sci USA 104(2):485–490. doi: 10.1073/pnas.0608090104 PubMedPubMedCentralCrossRefGoogle Scholar
  45. Inoue T, Shingaki R, Fukui K (2008) Inhibition of swarming motility of Pseudomonas aeruginosa by branched-chain fatty acids. FEMS Microbiol Lett 281(1):81–86. doi: 10.1111/j.1574-6968.2008.01089.x PubMedCrossRefGoogle Scholar
  46. Iwasaki A, Medzhitov R (2010) Regulation of adaptive immunity by the innate immune system. Science 327(5963):291–295. doi: 10.1126/science.1183021 PubMedPubMedCentralCrossRefGoogle Scholar
  47. Jarrell KF, McBride MJ (2008) The surprisingly diverse ways that prokaryotes move. Nat Rev Microbiol 6(6):466–476. doi: 10.1038/nrmicro1900 PubMedCrossRefGoogle Scholar
  48. Johnson TL, Abendroth J, Hol WG, Sandkvist M (2006) Type II secretion: from structure to function. FEMS Microbiol Lett 255(2):175–186. doi: 10.1111/j.1574-6968.2006.00102.x PubMedCrossRefGoogle Scholar
  49. Karlinsey JE, Tanaka S, Bettenworth V, Yamaguchi S, Boos W, Aizawa SI, Hughes KT (2000) Completion of the hook-basal body complex of the Salmonella typhimurium flagellum is coupled to FlgM secretion and fliC transcription. Mol Microbiol 37(5):1220–1231PubMedCrossRefGoogle Scholar
  50. Karuppiah V, Collins RF, Thistlethwaite A, Gao Y, Derrick JP (2013) Structure and assembly of an inner membrane platform for initiation of type IV pilus biogenesis. Proc Natl Acad Sci USA 110(48):E4638–E4647. doi: 10.1073/pnas.1312313110 PubMedPubMedCentralCrossRefGoogle Scholar
  51. Kauppi AM, Nordfelth R, Uvell H, Wolf-Watz H, Elofsson M (2003) Targeting bacterial virulence: inhibitors of type III secretion in Yersinia. Chem Biol 10(3):241–249PubMedCrossRefGoogle Scholar
  52. Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11(5):373–384. doi: 10.1038/ni.1863 PubMedCrossRefGoogle Scholar
  53. Kearns DB (2010) A field guide to bacterial swarming motility. Nat Rev Microbiol 8(9):634–644. doi: 10.1038/nrmicro2405 PubMedPubMedCentralCrossRefGoogle Scholar
  54. Kelly A, Goldberg MD, Carroll RK, Danino V, Hinton JC, Dorman CJ (2004) A global role for Fis in the transcriptional control of metabolism and type III secretion in Salmonella enterica serovar Typhimurium. Microbiology 150(Pt 7):2037–2053. doi: 10.1099/mic.0.27209-0 PubMedCrossRefGoogle Scholar
  55. Kim TJ, Young BM, Young GM (2008) Effect of flagellar mutations on Yersinia enterocolitica biofilm formation. Appl Environ Microbiol 74(17):5466–5474. doi: 10.1128/AEM.00222-08 PubMedPubMedCentralCrossRefGoogle Scholar
  56. Komeda Y, Suzuki H, Ishidsu JI, Iino T (1976) The role of cAMP in flagellation of Salmonella typhimurium. Mol Gen Genet MGG 142(4):289–298PubMedGoogle Scholar
  57. Krukonis ES, DiRita VJ (2003) From motility to virulence: sensing and responding to environmental signals in Vibrio cholerae. Curr Opin Microbiol 6(2):186–190PubMedCrossRefGoogle Scholar
  58. Kubori T, Yamaguchi S, Aizawa S (1997) Assembly of the switch complex onto the MS ring complex of Salmonella typhimurium does not require any other flagellar proteins. J Bacteriol 179(3):813–817PubMedPubMedCentralCrossRefGoogle Scholar
  59. Kutsukake K, Ohya Y, Iino T (1990) Transcriptional analysis of the flagellar regulon of Salmonella typhimurium. J Bacteriol 172(2):741–747PubMedPubMedCentralCrossRefGoogle Scholar
  60. Lee HJ, Hughes KT (2006) Posttranscriptional control of the Salmonella enterica flagellar hook protein FlgE. J Bacteriol 188(9):3308–3316. doi: 10.1128/JB.188.9.3308-3316.2006 PubMedPubMedCentralCrossRefGoogle Scholar
  61. Liu X, Matsumura P (1994) The FlhD/FlhC complex, a transcriptional activator of the Escherichia coli flagellar class II operons. J Bacteriol 176(23):7345–7351PubMedPubMedCentralCrossRefGoogle Scholar
  62. Lloyd SA, Tang H, Wang X, Billings S, Blair DF (1996) Torque generation in the flagellar motor of Escherichia coli: evidence of a direct role for FliG but not for FliM or FliN. J Bacteriol 178(1):223–231PubMedPubMedCentralCrossRefGoogle Scholar
  63. Lountos GT, Austin BP, Nallamsetty S, Waugh DS (2009) Atomic resolution structure of the cytoplasmic domain of Yersinia pestis YscU, a regulatory switch involved in type III secretion. Protein Sci Publ Protein Soc 18(2):467–474. doi: 10.1002/pro.56 CrossRefGoogle Scholar
  64. Macnab RM, Koshland DE Jr (1972) The gradient-sensing mechanism in bacterial chemotaxis. Proc Natl Acad Sci USA 69(9):2509–2512PubMedPubMedCentralCrossRefGoogle Scholar
  65. Manson MD, Tedesco P, Berg HC, Harold FM, Van der Drift C (1977) A protonmotive force drives bacterial flagella. Proc Natl Acad Sci USA 74(7):3060–3064PubMedPubMedCentralCrossRefGoogle Scholar
  66. Marchetti M, Sirard JC, Sansonetti P, Pringault E, Kerneis S (2004) Interaction of pathogenic bacteria with rabbit appendix M cells: bacterial motility is a key feature in vivo. Microbes Infect/Inst Pasteur 6(6):521–528. doi: 10.1016/j.micinf.2004.02.009 CrossRefGoogle Scholar
  67. Mariathasan S, Monack DM (2007) Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat Rev Immunol 7(1):31–40. doi: 10.1038/nri1997 PubMedCrossRefGoogle Scholar
  68. Martinez-Argudo I, Veenendaal AK, Liu X, Roehrich AD, Ronessen MC, Franzoni G, van Rietschoten KN, Morimoto YV, Saijo-Hamano Y, Avison MB, Studholme DJ, Namba K, Minamino T, Blocker AJ (2013) Isolation of Salmonella mutants resistant to the inhibitory effect of Salicylidene acylhydrazides on flagella-mediated motility. PLoS ONE 8(1):e52179. doi: 10.1371/journal.pone.0052179 PubMedPubMedCentralCrossRefGoogle Scholar
  69. Martins M, McCusker MP, McCabe EM, O’Leary D, Duffy G, Fanning S (2013) Evidence of metabolic switching and implications for food safety from the phenome(s) of Salmonella enterica serovar Typhimurium DT104 cultured at selected points across the pork production food chain. Appl Environ Microbiol 79(18):5437–5449. doi: 10.1128/AEM.01041-13 PubMedPubMedCentralCrossRefGoogle Scholar
  70. Mattick JS (2002) Type IV pili and twitching motility. Annu Rev Microbiol 56:289–314. doi: 10.1146/annurev.micro.56.012302.160938 PubMedCrossRefGoogle Scholar
  71. McBride MJ (2001) Bacterial gliding motility: multiple mechanisms for cell movement over surfaces. Annu Rev Microbiol 55:49–75. doi: 10.1146/annurev.micro.55.1.49 PubMedCrossRefGoogle Scholar
  72. McBride MJ, Zhu Y (2013) Gliding motility and Por secretion system genes are widespread among members of the phylum bacteroidetes. J Bacteriol 195(2):270–278. doi: 10.1128/JB.01962-12 PubMedPubMedCentralCrossRefGoogle Scholar
  73. Merino S, Shaw JG, Tomas JM (2006) Bacterial lateral flagella: an inducible flagella system. FEMS Microbiol Lett 263(2):127–135. doi: 10.1111/j.1574-6968.2006.00403.x PubMedCrossRefGoogle Scholar
  74. Merz AJ, So M, Sheetz MP (2000) Pilus retraction powers bacterial twitching motility. Nature 407(6800):98–102. doi: 10.1038/35024105 PubMedCrossRefGoogle Scholar
  75. Meshcheryakov VA, Kitao A, Matsunami H, Samatey FA (2013) Inhibition of a type III secretion system by the deletion of a short loop in one of its membrane proteins. Acta Crystallogr D Biol Crystallogr 69(Pt 5):812–820. doi: 10.1107/S0907444913002102 PubMedPubMedCentralCrossRefGoogle Scholar
  76. Miao EA, Alpuche-Aranda CM, Dors M, Clark AE, Bader MW, Miller SI, Aderem A (2006) Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf. Nat Immunol 7(6):569–575. doi: 10.1038/ni1344 PubMedCrossRefGoogle Scholar
  77. Minamino T, Namba K (2008) Distinct roles of the FliI ATPase and proton motive force in bacterial flagellar protein export. Nature 451(7177):485–488. doi: 10.1038/nature06449 PubMedCrossRefGoogle Scholar
  78. Minamino T, Ferris HU, Moriya N, Kihara M, Namba K (2006) Two parts of the T3S4 domain of the hook-length control protein FliK are essential for the substrate specificity switching of the flagellar type III export apparatus. J Mol Biol 362(5):1148–1158. doi: 10.1016/j.jmb.2006.08.004 PubMedCrossRefGoogle Scholar
  79. Mouslim C, Hughes KT (2014) The effect of cell growth phase on the regulatory cross-talk between flagellar and Spi1 virulence gene expression. PLoS Pathog 10(3):e1003987. doi: 10.1371/journal.ppat.1003987 PubMedPubMedCentralCrossRefGoogle Scholar
  80. Mouslim C, Delgado M, Groisman EA (2004) Activation of the RcsC/YojN/RcsB phosphorelay system attenuates Salmonella virulence. Mol Microbiol 54(2):386–395. doi: 10.1111/j.1365-2958.2004.04293.x PubMedCrossRefGoogle Scholar
  81. Mühlen S, Dersch P (2016) Anti-virulence strategies to target bacterial infections. Curr Top Microbiol Immunol. doi: 10.1007/82_2015_490 PubMedGoogle Scholar
  82. 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(39):14566–14571. doi: 10.1073/pnas.0606412103 PubMedPubMedCentralCrossRefGoogle Scholar
  83. Nakane D, Sato K, Wada H, McBride MJ, Nakayama K (2013) Helical flow of surface protein required for bacterial gliding motility. Proc Natl Acad Sci USA 110(27):11145–11150. doi: 10.1073/pnas.1219753110 PubMedPubMedCentralCrossRefGoogle Scholar
  84. Nordfelth R, Kauppi AM, Norberg HA, Wolf-Watz H, Elofsson M (2005) Small-molecule inhibitors specifically targeting type III secretion. Infect Immun 73(5):3104–3114. doi: 10.1128/IAI.73.5.3104-3114.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  85. Ohnishi K, Kutsukake K, Suzuki H, Lino T (1992) A novel transcriptional regulation mechanism in the flagellar regulon of Salmonella typhimurium: an antisigma factor inhibits the activity of the flagellum-specific sigma factor, sigma F. Mol Microbiol 6(21):3149–3157PubMedCrossRefGoogle Scholar
  86. Ottemann KM, Miller JF (1997) Roles for motility in bacterial-host interactions. Mol Microbiol 24(6):1109–1117PubMedCrossRefGoogle Scholar
  87. Oura H, Tashiro Y, Toyofuku M, Ueda K, Kiyokawa T, Ito S, Takahashi Y, Lee S, Nojiri H, Nakajima-Kambe T, Uchiyama H, Futamata H, Nomura N (2015) Inhibition of Pseudomonas aeruginosa swarming motility by 1-naphthol and other bicyclic compounds bearing hydroxyl groups. Appl Environ Microbiol 81(8):2808–2818. doi: 10.1128/AEM.04220-14 PubMedPubMedCentralCrossRefGoogle Scholar
  88. Paschos A, den Hartigh A, Smith MA, Atluri VL, Sivanesan D, Tsolis RM, Baron C (2011) An in vivo high-throughput screening approach targeting the type IV secretion system component VirB8 identified inhibitors of Brucella abortus 2308 proliferation. Infect Immun 79(3):1033–1043. doi: 10.1128/IAI.00993-10 PubMedCrossRefGoogle Scholar
  89. Paul K, Erhardt M, Hirano T, Blair DF, Hughes KT (2008) Energy source of flagellar type III secretion. Nature 451(7177):489–492. doi: 10.1038/nature06497 PubMedCrossRefGoogle Scholar
  90. Peabody CR, Chung YJ, Yen MR, Vidal-Ingigliardi D, Pugsley AP, Saier MH Jr (2003) Type II protein secretion and its relationship to bacterial type IV pili and archaeal flagella. Microbiology 149(Pt 11):3051–3072PubMedCrossRefGoogle Scholar
  91. Pratt LA, Kolter R (1998) Genetic analysis of Escherichia coli biofilm formation: roles of flagella, motility, chemotaxis and type I pili. Mol Microbiol 30(2):285–293PubMedCrossRefGoogle Scholar
  92. Rasmussen L, White EL, Pathak A, Ayala JC, Wang H, Wu JH, Benitez JA, Silva AJ (2011) A high-throughput screening assay for inhibitors of bacterial motility identifies a novel inhibitor of the Na+-driven flagellar motor and virulence gene expression in Vibrio cholerae. Antimicrob Agents Chemother 55(9):4134–4143. doi: 10.1128/AAC.00482-11 PubMedPubMedCentralCrossRefGoogle Scholar
  93. Rossez Y, Wolfson EB, Holmes A, Gally DL, Holden NJ (2015) Bacterial flagella: twist and stick, or dodge across the kingdoms. PLoS Pathog 11(1):e1004483. doi: 10.1371/journal.ppat.1004483 PubMedPubMedCentralCrossRefGoogle Scholar
  94. Roy K, Hilliard GM, Hamilton DJ, Luo J, Ostmann MM, Fleckenstein JM (2009) Enterotoxigenic Escherichia coli EtpA mediates adhesion between flagella and host cells. Nature 457(7229):594–598. doi: 10.1038/nature07568 PubMedCrossRefGoogle Scholar
  95. Salzer R, Joos F, Averhoff B (2014) Type IV pilus biogenesis, twitching motility, and DNA uptake in Thermus thermophilus: discrete roles of antagonistic ATPases PilF, PilT1, and PilT2. Appl Environ Microbiol 80(2):644–652. doi: 10.1128/AEM.03218-13 PubMedPubMedCentralCrossRefGoogle Scholar
  96. Sato Y, Takaya A, Mouslim C, Hughes KT, Yamamoto T (2014) FliT selectively enhances proteolysis of FlhC subunit in FlhD4C2 complex by an ATP-dependent protease, ClpXP. J Biol Chem 289(47):33001–33011. doi: 10.1074/jbc.M114.593749 PubMedPubMedCentralCrossRefGoogle Scholar
  97. Schmitt CK, Darnell SC, Tesh VL, Stocker BA, O’Brien AD (1994) Mutation of flgM attenuates virulence of Salmonella typhimurium, and mutation of fliA represses the attenuated phenotype. J Bacteriol 176(2):368–377PubMedPubMedCentralCrossRefGoogle Scholar
  98. Schmitt CK, Darnell SC, O’Brien AD (1996) The attenuated phenotype of a Salmonella typhimurium flgM mutant is related to expression of FliC flagellin. J Bacteriol 178(10):2911–2915PubMedPubMedCentralCrossRefGoogle Scholar
  99. Shin S, Park C (1995) Modulation of flagellar expression in Escherichia coli by acetyl phosphate and the osmoregulator OmpR. J Bacteriol 177(16):4696–4702PubMedPubMedCentralCrossRefGoogle Scholar
  100. Singer HM, Kuhne C, Deditius JA, Hughes KT, Erhardt M (2014) The Salmonella Spi1 virulence regulatory protein HilD directly activates transcription of the flagellar master operon flhDC. J Bacteriol 196(7):1448–1457. doi: 10.1128/JB.01438-13 PubMedPubMedCentralCrossRefGoogle Scholar
  101. Stecher B, Hapfelmeier S, Muller C, Kremer M, Stallmach T, Hardt WD (2004) Flagella and chemotaxis are required for efficient induction of Salmonella enterica serovar Typhimurium colitis in streptomycin-pretreated mice. Infect Immun 72(7):4138–4150. doi: 10.1128/IAI.72.7.4138-4150.2004 PubMedPubMedCentralCrossRefGoogle Scholar
  102. Stecher B, Barthel M, Schlumberger MC, Haberli L, Rabsch W, Kremer M, Hardt WD (2008) Motility allows S. Typhimurium to benefit from the mucosal defence. Cell Microbiol 10(5):1166–1180. doi: 10.1111/j.1462-5822.2008.01118.x PubMedCrossRefGoogle Scholar
  103. Stojiljkovic I, Baumler AJ, Hantke K (1994) Fur regulon in gram-negative bacteria. Identification and characterization of new iron-regulated Escherichia coli genes by a fur titration assay. J Mol Biol 236(2):531–545. doi: 10.1006/jmbi.1994.1163 PubMedCrossRefGoogle Scholar
  104. Swietnicki W, Carmany D, Retford M, Guelta M, Dorsey R, Bozue J, Lee MS, Olson MA (2011) Identification of small-molecule inhibitors of Yersinia pestis Type III secretion system YscN ATPase. PLoS ONE 6(5):e19716. doi: 10.1371/journal.pone.0019716 PubMedPubMedCentralCrossRefGoogle Scholar
  105. Takaya A, Erhardt M, Karata K, Winterberg K, Yamamoto T, Hughes KT (2012) YdiV: a dual function protein that targets FlhDC for ClpXP-dependent degradation by promoting release of DNA-bound FlhDC complex. Mol Microbiol 83(6):1268–1284. doi: 10.1111/j.1365-2958.2012.08007.x PubMedPubMedCentralCrossRefGoogle Scholar
  106. Toker AS, Macnab RM (1997) Distinct regions of bacterial flagellar switch protein FliM interact with FliG, FliN and CheY. J Mol Biol 273(3):623–634. doi: 10.1006/jmbi.1997.1335 PubMedCrossRefGoogle Scholar
  107. Tsang N, Macnab R, Koshland DE Jr (1973) Common mechanism for repellents and attractants in bacterial chemotaxis. Science 181(4094):60–63PubMedCrossRefGoogle Scholar
  108. van Asten FJ, Hendriks HG, Koninkx JF, van Dijk JE (2004) Flagella-mediated bacterial motility accelerates but is not required for Salmonella serotype Enteritidis invasion of differentiated Caco-2 cells. Int J Med Microbiol IJMM 294(6):395–399. doi: 10.1016/j.ijmm.2004.07.012 PubMedCrossRefGoogle Scholar
  109. Varga JJ, Nguyen V, O’Brien DK, Rodgers K, Walker RA, Melville SB (2006) Type IV pili-dependent gliding motility in the Gram-positive pathogen Clostridium perfringens and other Clostridia. Mol Microbiol 62(3):680–694. doi: 10.1111/j.1365-2958.2006.05414.x PubMedCrossRefGoogle Scholar
  110. Wang S, Fleming RT, Westbrook EM, Matsumura P, McKay DB (2006) Structure of the Escherichia coli FlhDC complex, a prokaryotic heteromeric regulator of transcription. J Mol Biol 355(4):798–808. doi: 10.1016/j.jmb.2005.11.020 PubMedCrossRefGoogle Scholar
  111. Wang Q, Zhao Y, McClelland M, Harshey RM (2007) The RcsCDB signaling system and swarming motility in Salmonella enterica serovar typhimurium: dual regulation of flagellar and SPI-2 virulence genes. J Bacteriol 189(23):8447–8457. doi: 10.1128/JB.01198-07 PubMedPubMedCentralCrossRefGoogle Scholar
  112. Wei BL, Brun-Zinkernagel AM, Simecka JW, Pruss BM, Babitzke P, Romeo T (2001) Positive regulation of motility and flhDC expression by the RNA-binding protein CsrA of Escherichia coli. Mol Microbiol 40(1):245–256PubMedCrossRefGoogle Scholar
  113. Williams SM, Chen YT, Andermann TM, Carter JE, McGee DJ, Ottemann KM (2007) Helicobacter pylori chemotaxis modulates inflammation and bacterium-gastric epithelium interactions in infected mice. Infect Immun 75(8):3747–3757. doi: 10.1128/IAI.00082-07 PubMedPubMedCentralCrossRefGoogle Scholar
  114. Yakhnin AV, Baker CS, Vakulskas CA, Yakhnin H, Berezin I, Romeo T, Babitzke P (2013) CsrA activates flhDC expression by protecting flhDC mRNA from RNase E-mediated cleavage. Mol Microbiol 87(4):851–866. doi: 10.1111/mmi.12136 PubMedPubMedCentralCrossRefGoogle Scholar
  115. Yanagihara S, Iyoda S, Ohnishi K, Iino T, Kutsukake K (1999) Structure and transcriptional control of the flagellar master operon of Salmonella typhimurium. Genes Genet Syst 74(3):105–111PubMedCrossRefGoogle Scholar
  116. Yang X, Thornburg T, Suo Z, Jun S, Robison A, Li J, Lim T, Cao L, Hoyt T, Avci R, Pascual DW (2012) Flagella overexpression attenuates Salmonella pathogenesis. PLoS ONE 7(10):e46828. doi: 10.1371/journal.pone.0046828 PubMedPubMedCentralCrossRefGoogle Scholar
  117. Yonekura K, Maki-Yonekura S, Namba K (2003) Complete atomic model of the bacterial flagellar filament by electron cryomicroscopy. Nature 424(6949):643–650. doi: 10.1038/nature01830 PubMedCrossRefGoogle Scholar
  118. Young GM, Badger JL, Miller VL (2000) Motility is required to initiate host cell invasion by Yersinia enterocolitica. Infect Immun 68(7):4323–4326PubMedPubMedCentralCrossRefGoogle Scholar
  119. Zarivach R, Vuckovic M, Deng W, Finlay BB, Strynadka NC (2007) Structural analysis of a prototypical ATPase from the type III secretion system. Nat Struct Mol Biol 14(2):131–137. doi: 10.1038/nsmb1196 PubMedCrossRefGoogle Scholar
  120. Zarivach R, Deng W, Vuckovic M, Felise HB, Nguyen HV, Miller SI, Finlay BB, Strynadka NC (2008) Structural analysis of the essential self-cleaving type III secretion proteins EscU and SpaS. Nature 453(7191):124–127. doi: 10.1038/nature06832 PubMedCrossRefGoogle Scholar
  121. Zhang X, Kelly SM, Bollen WS, Curtiss R 3rd (1997) Characterization and immunogenicity of Salmonella typhimurium SL1344 and UK-1 delta crp and delta cdt deletion mutants. Infect Immun 65(12):5381–5387PubMedPubMedCentralGoogle Scholar
  122. Zhao R, Amsler CD, Matsumura P, Khan S (1996a) FliG and FliM distribution in the Salmonella typhimurium cell and flagellar basal bodies. J Bacteriol 178(1):258–265PubMedPubMedCentralCrossRefGoogle Scholar
  123. Zhao R, Pathak N, Jaffe H, Reese TS, Khan S (1996b) FliN is a major structural protein of the C-ring in the Salmonella typhimurium flagellar basal body. J Mol Biol 261(2):195–208. doi: 10.1006/jmbi.1996.0452 PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Helmholtz Centre for Infection ResearchBraunschweigGermany

Personalised recommendations