Chapter 1 : Type III Secretory Proteins in

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Type III Secretory Proteins in , Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815851/9781555814694_Chap01-1.gif /docserver/preview/fulltext/10.1128/9781555815851/9781555814694_Chap01-2.gif


is a normal inhabitant of soil and water and is ubiquitous in the environment. Importantly, uses additional bacterial products encoded by the T3SS to directly deliver enzymes into cells to alter host physiology. This chapter summarizes the discovery, molecular properties, and host cofactors of the T3SS-delivered enzymes of . The first identified T3SS effector, exoenzyme S (ExoS), was actually discovered before the components of the secretory system in were known. The data argues that ExoS traffics within host cells and that some of the biological consequences of ExoS delivery may be related to its localization. The chapter focuses on the biological and biochemical implications of the need for eukaryotic cofactors for bacterial toxin activity by using the studies of the enzymatic activity of ExoU as a paradigm. The T3SS and the effector proteins encoded by provide model systems for fundamental studies of host-pathogen relationships and the expression of virulence factors relative to the pathological consequences of infection. The opportunistic nature of infections suggests that the acquisition and maintenance of the genes encoding the T3SS provide the bacterium with a selective advantage in the environment. The identification of cofactors that are ubiquitous in eukaryotic organisms but not present or active in prokaryotes and the linkage to type III secretion may reveal unique mechanisms to ensure the specific targeting of the toxin.

Citation: Sato H, Frank D. 2007. Type III Secretory Proteins in , p 3-22. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch1
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Functional domains in type III effector proteins. encodes four enzymes, ExoS, ExoT, ExoY, and ExoU, that are injected into eukaryotic cells by the T3SS. Important functional domains, denoted by boxes with amino acid sequence boundaries, are shown. ExoS and ExoT contain MLDs and require R146 and R149 for GAP activity and E381 and E383 for ADP-ribosyltransferase (ADP-r) activity, respectively. The sequence DALDL (amino acids 424 to 428) in ExoS is critical for 14-3-3 cofactor binding. Two conserved regions in ExoY, an ATP-GTP binding motif and a β- and γ-phosphate interaction motif (PIM), align with corresponding regions of other bacterial adenylyl cyclases, CyaA () and EF (). The N-terminal half of ExoU contains residues for a PLA catalytic dyad, S142 and D344, and a glycine-rich motif (GXSXG, amino acids 111 to 116 [where X represents any residue]). The C-terminal (C-term) domain of ExoU is also important for enzymatic activity and may contain sequences required for cofactor binding, the recognition of membrane substrates, ubiquitinylation, or localization. The N-terminal regions of all four enzymes contain sequences required for type III secretion and binding sites for their respective cognate chaperone proteins (data not shown).

Citation: Sato H, Frank D. 2007. Type III Secretory Proteins in , p 3-22. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch1
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

ExoU damages host membranes in vivo. A control strain expressing β-galactosidase demonstrates smooth vacuolar morphology with Nomarski interference microscopy (bottom left panel). Quinacrine staining generally reveals a single vacuole and few acidic vesicles (top left panel). Strains expressing ExoU (5 h of induction; right panels) demonstrate a vacuole fragmentation phenotype (numerous acidic vesicles). These data suggest that ExoU-mediated vacuolar fragmentation is due to the breakdown of vacuoles and not a failure of vacuolar biogenesis.

Citation: Sato H, Frank D. 2007. Type III Secretory Proteins in , p 3-22. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch1
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

The preincubation of rExoU with yeast extract does not accelerate enzyme activation. rExoU (1 µg) was preincubated with 2.5 µg of yeast extract for 30 min (solid squares), followed by the addition of radiolabeled liposomes. Phospholipase activity levels were measured after 1, 2, and 3 h of incubation at 30°C. The kinetics of substrate (1-palmitoyl-2-oleoylphosphatidylcholine [POPC] hydrolysis after preincubation were similar to those of a control with no preincubation (0 min, open triangles).

Citation: Sato H, Frank D. 2007. Type III Secretory Proteins in , p 3-22. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch1
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Noncatalytic forms of rExoU compete with the wild-type enzyme. Wild-type (WT) rExoU (2.5 µg; 33.8 pmol) and 5 µg of yeast soluble extract were used in the competition studies. The following noncatalytic forms of rExoU were added to the reaction mixture: 343-687U (gray squares), an rExoU mutant with a truncation of the N-terminal domain, and S142A (solid diamonds), a form of rExoU with a site-specific alanine substitution at the serine catalytic site. rPcrV (open triangles), a T3SS-secreted protein, was used as a negative control. Phospholipase activity levels are represented as percentages of the positive control (the activity level of wild-type rExoU) at various molar ratios of a competitor of the wild-type enzyme. The phospholipase activity of the wild-type enzyme was inhibited more than 90% by S142A and 70% by 343-687U, suggesting that the noncatalytic molecules compete with the wild-type enzyme for a common cofactor.

Citation: Sato H, Frank D. 2007. Type III Secretory Proteins in , p 3-22. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch1
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Apodaca, G.,, M. Bomsel,, R. Lindstedt,, J. Engel,, D. Frank,, K. E. Mostov, and, J. Wiener-Kronish. 1995. Characterization of Pseudomonas aeruginosa-induced MDCK cell injury: glycosylation-defective host cells are resistant to bacterial killing. Infect. Immun. 63: 15411551.
2. Barker, A. P.,, A. I. Vasil,, A. Filloux,, G. Ball,, P. J. Wilderman, and, M. L. Vasil. 2004. A novel extracellular phospholipase C of Pseudomonas aeruginosa is required for phospholipid chemotaxis. Mol. Microbiol. 53: 10891098.
3. Bette-Bobillo, P.,, P. Giro,, J. Sainte-Marie, and, M. Vidal. 1998. Exoenzyme S from P. aeruginosa ADP ribosylates rab4 and inhibits transferrin recycling in SLO-permeabilized reticulocytes. Biochem. Biophys. Res. Commun. 244: 336341.
4. Borchelt, D. R.,, M. K. Lee,, H. S. Slunt,, M. Guarnieri,, Z. S. Xu,, P. C. Wong,, R. H. Brown, Jr.,, D. L. Price,, S. S. Sisodia, and, D. W. Cleveland. 1994. Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc. Natl. Acad. Sci. USA 91: 82928296.
5. Buday, L. 1999. Membrane-targeting of signalling molecules by SH2/SH3 domain-containing adaptor proteins. Biochim. Biophys. Acta 1422: 187204.
6. Coburn, J.,, S. T. Dillon,, B. H. Iglewski, and, D. M. Gill. 1989. Exoenzyme S of Pseudomonas aeruginosa ADP-ribosylates the intermediate filament protein vimentin. Infect. Immun. 57: 996998.
7. Coburn, J., and, D. M. Gill. 1991. ADP-ribosylation of p21ras and related proteins by Pseudomonas aeruginosa exoenzyme S. Infect. Immun. 59: 42594262.
8. Coburn, J.,, A. V. Kane,, L. Feig, and, D. M. Gill. 1991. Pseudomonas aeruginosa exoenzyme S requires a eukaryotic protein for ADP-ribosyltransferase activity. J. Biol. Chem. 266: 64386446.
9. Coburn, J.,, R. T. Wyatt,, B. H. Iglewski, and, D. M. Gill. 1989. Several GTP-binding proteins, including p21c-H-ras, are preferred substrates of Pseudomonas aeruginosa exoenzyme S. J. Biol. Chem. 264: 90049008.
10. Cornelis, G. R. 2006. The type III secretion injectisome. Nat. Rev. Microbiol. 4: 811825.
11. Dacheux, D.,, B. Toussaint,, M. Richard,, G. Brochier,, J. Croize, and, I. Attree. 2000. Pseudomonas aeruginosa cystic fibrosis isolates induce rapid, type III secretion-dependent, but ExoU-independent, oncosis of macrophages and polymorphonuclear neutrophils. Infect. Immun. 68: 29162924.
12. D’Argenio, D. A.,, L. A. Gallagher,, C. A. Berg, and, C. Manoil. 2001. Drosophila as a model host for Pseudomonas aeruginosa infection. J. Bacteriol. 183: 14661471.
13. Dasgupta, N.,, A. Ashare,, G. W. Hunninghake, and, T. L. Yahr. 2006. Transcriptional induction of the Pseudomonas aeruginosa type III secretion system by low Ca 2+ and host cell contact proceeds through two distinct signaling pathways. Infect. Immun. 74: 33343341.
14. Deng, H. X.,, A. Hentati,, J. A. Tainer,, Z. Iqbal,, A. Cayabyab,, W. Y. Hung,, E. D. Getzoff,, P. Hu,, B. Herzfeldt,, R. P. Roos, et al. 1993. Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase. Science 261: 10471051.
15. Deng, Q.,, J. Sun, and, J. T. Barbieri. 2005. Uncoupling Crk signal transduction by Pseudomonas exoenzyme T. J. Biol. Chem. 280: 3595335960.
16. Dessen, A.,, J. Tang,, H. Schmidt,, M. Stahl,, J. D. Clark,, J. Seehra, and, W. S. Somers. 1999. Crystal structure of human cytosolic phospholipase A(2) reveals a novel topology and catalytic mechanism. Cell 97: 349360.
17. DiMango, E.,, A. J. Ratner,, R. Bryan,, S. Tabibi, and, A. Prince. 1998. Activation of NF-kappaB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells. J. Clin. Investig. 101: 25982605.
18. DiMango, E.,, H. J. Zar,, R. Bryan, and, A. Prince. 1995. Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8. J. Clin. Investig. 96: 22042210.
19. DiNovo, A. A.,, K. L. Schey,, W. S. Vachon,, E. M. McGuffie,, J. C. Olson, and, T. S. Vincent. 2006. ADP-ribosylation of cyclophilin A by Pseudomonas aeruginosa exoenzyme S. Biochemistry 45: 46644673.
20. Drenkard, E., and, F. M. Ausubel. 2002. Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 416: 740743.
21. Ernst, R. K.,, E. C. Yi,, L. Guo,, K. B. Lim,, J. L. Burns,, M. Hackett, and, S. I. Miller. 1999. Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa. Science 286: 15611565.
22. Escuyer, V.,, E. Duflot,, O. Sezer,, A. Danchin, and, M. Mock. 1988. Structural homology between virulence-associated bacterial adenylate cyclases. Gene 71: 293298.
23. Fattman, C. L.,, J. J. Enghild,, J. D. Crapo,, L. M. Schaefer,, Z. Valnickova, and, T. D. Oury. 2000. Purification and characterization of extracellular superoxide dismutase in mouse lung. Biochem. Biophys. Res. Commun. 275: 542548.
24. Feller, S. M. 2001. Crk family adaptors-signalling complex formation and biological roles. Oncogene 20: 63486371.
25. Filiatrault, M. J.,, K. F. Picardo,, H. Ngai,, L. Passador, and, B. H. Iglewski. 2006. Identification of Pseudomonas aeruginosa genes involved in virulence and anaerobic growth. Infect. Immun. 74: 42374245.
26. Finck-Barbançon, V., and, D. W. Frank. 2001. Multiple domains are required for the toxic activity of Pseudomonas aeruginosa ExoU. J. Bacteriol. 183: 43304344.
27. Finck-Barbançon, V.,, J. Goranson,, L. Zhu,, T. Sawa,, J. P. Wiener-Kronish,, S. M. Fleiszig,, C. Wu,, L. Mende-Mueller, and, D. W. Frank. 1997. ExoU expression by Pseudomonas aeruginosa correlates with acute cytotoxicity and epithelial injury. Mol. Microbiol. 25: 547557.
28. Fleiszig, S. M., and, D. J. Evans. 2003. Contact lens infections: can they ever be eradicated? Eye Contact Lens 29: S67S71.
29. Fleiszig, S. M.,, D. J. Evans,, N. Do,, V. Vallas,, S. Shin, and, K. E. Mostov. 1997. Epithelial cell polarity affects susceptibility to Pseudomonas aeruginosa invasion and cytotoxicity. Infect. Immun. 65: 28612867.
30. Folz, R. J.,, J. Guan,, M. F. Seldin,, T. D. Oury,, J. J. Enghild, and, J. D. Crapo. 1997. Mouse extracellular superoxide dismutase: primary structure, tissue-specific gene expression, chromosomal localization, and lung in situ hybridization. Am. J. Respir. Cell Mol. Biol. 17: 393403.
31. Ford, J. C.,, F. al Khodairy,, E. Fotou,, K. S. Sheldrick,, D. J. Griffiths, and, A. M. Carr. 1994. 14-3-3 protein homologs required for the DNA damage checkpoint in fission yeast. Science 265: 533535.
32. Frank, D. W., and, B. H. Iglewski. 1991. Cloning and sequence analysis of a trans-regulatory locus required for exoenzyme S synthesis in Pseudomonas aeruginosa. J. Bacteriol. 173: 64606468.
33. Fraylick, J. E.,, M. J. Riese,, T. S. Vincent,, J. T. Barbieri, and, J. C. Olson. 2002. ADP-ribosylation and functional effects of Pseudomonas exoenzyme S on cellular RalA. Biochemistry 41: 96809687.
34. Fraylick, J. E.,, E. A. Rucks,, D. M. Greene,, T. S. Vincent, and, J. C. Olson. 2002. Eukaryotic cell determination of ExoS ADP-ribosyltransferase substrate specificity. Biochem. Biophys. Res. Commun. 291: 91100.
35. Fridovich, I. 1975. Superoxide dismutases. Annu. Rev. Biochem. 44: 147159.
36. Fridovich, I. 1989. Superoxide dismutases. An adaptation to a paramagnetic gas. J. Biol. Chem. 264: 77617764.
37. Frithz-Lindsten, E.,, Y. Du,, R. Rosqvist, and, A. Forsberg. 1997. Intracellular targeting of exoenzyme S of Pseudomonas aeruginosa via type III-dependent translocation induces phagocytosis resistance, cytotoxicity and disruption of actin microfilaments. Mol. Microbiol. 25: 11251139.
38. Fu, H.,, J. Coburn, and, R. J. Collier. 1993. The eukaryotic host factor that activates exoenzyme S of Pseudomonas aeruginosa is a member of the 14-3-3 protein family. Proc. Natl. Acad. Sci. USA 90: 23202324.
39. Garrity-Ryan, L.,, B. Kazmierczak,, R. Kowal,, J. Comolli,, A. Hauser, and, J. N. Engel. 2000. The arginine finger domain of ExoT contributes to actin cytoskeleton disruption and inhibition of internalization of Pseudomonas aeruginosa by epithelial cells and macrophages. Infect. Immun. 68: 71007113.
40. Garrity-Ryan, L.,, S. Shafikhani,, P. Balachandran,, L. Nguyen,, J. Oza,, T. Jakobsen,, J. Sargent,, X. Fang,, S. Cordwell,, M. A. Matthay, and, J. N. Engel. 2004. The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to its biological activities. Infect. Immun. 72: 546558.
41. Geiser, T. K.,, B. I. Kazmierczak,, L. K. Garrity-Ryan,, M. A. Matthay, and, J. N. Engel. 2001. Pseudomonas aeruginosa ExoT inhibits in vitro lung epithelial wound repair. Cell. Microbiol. 3: 223236.
42. Gelperin, D.,, J. Weigle,, K. Nelson,, P. Roseboom,, K. Irie,, K. Matsumoto, and, S. Lemmon. 1995. 14-3-3 proteins: potential roles in vesicular transport and Ras signaling in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 92: 1153911543.
43. Gillis, R. J.,, K. G. White,, K. H. Choi,, V. E. Wagner,, H. P. Schweizer, and, B. H. Iglewski. 2005. Molecular basis of azithromycin-resistant Pseudomonas aeruginosa biofilms. Antimicrob. Agents Chemother. 49: 38583867.
44. Glaser, P.,, H. Munier,, A. M. Gilles,, E. Krin,, T. Porumb,, O. Barzu,, R. Sarfati,, C. Pellecuer, and, A. Danchin. 1991. Functional consequences of single amino acid substitutions in calmodulin-activated adenylate cyclase of Bordetella pertussis. EMBO J. 10: 16831688.
45. Goehring, U. M.,, G. Schmidt,, K. J. Pederson,, K. Aktories, and, J. T. Barbieri. 1999. The N-terminal domain of Pseudomonas aeruginosa exoenzyme S is a GTPase-activating protein for Rho GTPases. J. Biol. Chem. 274: 3636936372.
46. Goodman, A. L.,, B. Kulasekara,, A. Rietsch,, D. Boyd,, R. S. Smith, and, S. Lory. 2004. A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa. Dev. Cell 7: 745754.
47. Govan, J. R., and, V. Deretic. 1996. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol. Rev. 60: 539574.
48. Gurney, M. E.,, H. Pu,, A. Y. Chiu,, M. C. Dal Canto,, C. Y. Polchow,, D. D. Alexander,, J. Caliendo,, A. Hentati,, Y. W. Kwon,, H. X. Deng, et al. 1994. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264: 17721775.
49. Hanna, S. L.,, N. E. Sherman,, M. T. Kinter, and, J. B. Goldberg. 2000. Comparison of proteins expressed by Pseudomonas aeruginosa strains representing initial and chronic isolates from a cystic fibrosis patient: an analysis by 2-D gel electrophoresis and capillary column liquid chromatography-tandem mass spectrometry. Microbiology 146: 24952508.
50. Hauser, A. R.,, P. J. Kang, and, J. N. Engel. 1998. PepA, a secreted protein of Pseudomonas aeruginosa, is necessary for cytotoxicity and virulence. Mol. Microbiol. 27: 807818.
51. Henriksson, M. L.,, M. S. Francis,, A. Peden,, M. Aili,, K. Stefansson,, R. Palmer,, A. Aitken, and, B. Hallberg. 2002. A nonphosphorylated 14-3-3 binding motif on exoenzyme S that is functional in vivo. Eur. J. Biochem. 269: 49214929.
52. Henriksson, M. L.,, C. Sundin,, A. L. Jansson,, A. Forsberg,, R. H. Palmer, and, B. Hallberg. 2002. Exoenzyme S shows selective ADP-ribosylation and GTPase-activating protein (GAP) activities towards small GTPases in vivo. Biochem. J. 367: 617628.
53. Iglewski, B. H.,, J. Sadoff,, M. J. Bjorn, and, E. S. Maxwell. 1978. Pseudomonas aeruginosa exoenzyme S: an adenosine diphosphate ribosyltransferase distinct from toxin A. Proc. Natl. Acad. Sci. USA 75: 32113215.
54. Jander, G.,, L. G. Rahme, and, F. M. Ausubel. 2000. Positive correlation between virulence of Pseudomonas aeruginosa mutants in mice and insects. J. Bacteriol. 182: 38433845.
55. Kang, P. J.,, A. R. Hauser,, G. Apodaca,, S. M. Fleiszig,, J. Wiener-Kronish,, K. Mostov, and, J. N. Engel. 1997. Identification of Pseudomonas aeruginosa genes required for epithelial cell injury. Mol. Microbiol. 24: 12491262.
56. Kazmierczak, B. I., and, J. N. Engel. 2002. Pseudomonas aeruginosa ExoT acts in vivo as a GTPase-activating protein for RhoA, Rac1, and Cdc42. Infect. Immun. 70: 21982205.
57. Kim, Y. J.,, R. Nakatomi,, T. Akagi,, T. Hashikawa, and, R. Takahashi. 2005. Unsaturated fatty acids induce cytotoxic aggregate formation of amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutants. J. Biol. Chem. 280: 2151521521.
58. Kinnula, V. L., and, J. D. Crapo. 2003. Superoxide dismutases in the lung and human lung diseases. Am. J. Respir. Crit. Care Med. 167: 16001619.
59. Knight, D. A.,, V. Finck-Barbançon,, S. M. Kulich, and, J. T. Barbieri. 1995. Functional domains of Pseudomonas aeruginosa exoenzyme S. Infect. Immun. 63: 31823186.
60. Kong, F.,, L. Young,, Y. Chen,, H. Ran,, M. Meyers,, P. Joseph,, Y. H. Cho,, D. J. Hassett, and, G. W. Lau. 2006. Pseudomonas aeruginosa pyocyanin inactivates lung epithelial vacuolar ATPase-dependent cystic fibrosis transmembrane conductance regulator expression and localization. Cell. Microbiol. 8: 11211133.
61. Krall, R.,, G. Schmidt,, K. Aktories, and, J. T. Barbieri. 2000. Pseudomonas aeruginosa ExoT is a Rho GTPase-activating protein. Infect. Immun. 68: 60666068.
62. Krall, R.,, Y. Zhang, and, J. T. Barbieri. 2004. Intracellular membrane localization of Pseudomonas ExoS and Yersinia YopE in mammalian cells. J. Biol. Chem. 279: 27472753.
63. Kudoh, I.,, J. P. Wiener-Kronish,, S. Hashimoto,, J. F. Pittet, and, D. Frank. 1994. Exoproduct secretions of Pseudomonas aeruginosa strains influence severity of alveolar epithelial injury. Am. J. Physiol. 267: L551L556.
64. Kulasakara, H.,, V. Lee,, A. Brencic,, N. Liberati,, J. Urbach,, S. Miyata,, D. G. Lee,, A. N. Neely,, M. Hyodo,, Y. Hayakawa,, F. M. Ausubel, and, S. Lory. 2006. Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence. Proc. Natl. Acad. Sci. USA 103: 28392844.
65. Kulich, S. M.,, D. W. Frank, and, J. T. Barbieri. 1995. Expression of recombinant exoenzyme S of Pseudomonas aeruginosa. Infect. Immun. 63: 18.
66. Kulich, S. M.,, T. L. Yahr,, L. M. Mende-Mueller,, J. T. Barbieri, and, D. W. Frank. 1994. Cloning the structural gene for the 49-kDa form of exoenzyme S (exoS) from Pseudomonas aeruginosa strain 388. J. Biol. Chem. 269: 1043110437.
67. Kurahashi, K.,, O. Kajikawa,, T. Sawa,, M. Ohara,, M. A. Gropper,, D. W. Frank,, T. R. Martin, and, J. P. Wiener-Kronish. 1999. Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J. Clin. Investig. 104: 743750.
68. Lamb, A. L.,, A. S. Torres,, T. V. O’Halloran, and, A. C. Rosenzweig. 2001. Heterodimeric structure of superoxide dismutase in complex with its metallochaperone. Nat. Struct. Biol. 8: 751755.
69. Laskowski, M. A., and, B. I. Kazmierczak. 2006. Mutational analysis of RetS, an unusual sensor kinase-response regulator hybrid required for Pseudomonas aeruginosa virulence. Infect. Immun. 74: 44624473.
70. Laskowski, M. A.,, E. Osborn, and, B. I. Kazmierczak. 2004. A novel sensor kinase-response regulator hybrid regulates type III secretion and is required for virulence in Pseudomonas aeruginosa. Mol. Microbiol. 54: 10901103.
71. Lau, G. W.,, B. C. Goumnerov,, C. L. Walendziewicz,, J. Hewitson,, W. Xiao,, S. MahajanMiklos,, R. G. Tompkins,, L. A. Perkins, and, L. G. Rahme. 2003. The Drosophila melanogaster Toll pathway participates in resistance to infection by the gram-negative human pathogen Pseudomonas aeruginosa. Infect. Immun. 71: 40594066.
72. Lee, V. T.,, R. S. Smith,, B. Tummler, and, S. Lory. 2005. Activities of Pseudomonas aeruginosa effectors secreted by the type III secretion system in vitro and during infection. Infect. Immun. 73: 16951705.
73. Li, J. D.,, A. F. Dohrman,, M. Gallup,, S. Miyata,, J. R. Gum,, Y. S. Kim,, J. A. Nadel,, A. Prince, and, C. B. Basbaum. 1997. Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proc. Natl. Acad. Sci. USA 94: 967972.
74. Li, S.,, P. Janosch,, M. Tanji,, G. C. Rosenfeld,, J. C. Waymire,, H. Mischak,, W. Kolch, and, J. M. Sedivy. 1995. Regulation of Raf-1 kinase activity by the 14-3-3 family of proteins. EMBO J. 14: 685696.
75. Lindberg, M. J.,, R. Bystrom,, N. Boknas,, P. M. Andersen, and, M. Oliveberg. 2005. Systematically perturbed folding patterns of amyotrophic lateral sclerosis (ALS)-associated SOD1 mutants. Proc. Natl. Acad. Sci. USA 102: 97549759.
76. Liu, S.,, S. M. Kulich, and, J. T. Barbieri. 1996. Identification of glutamic acid 381 as a candidate active site residue of Pseudomonas aeruginosa exoenzyme S. Biochemistry 35: 27542758.
77. Lowe, M. E. 2002. The triglyceride lipases of the pancreas. J. Lipid Res. 43: 20072016.
78. Mackintosh, C. 2004. Dynamic interactions between 14-3-3 proteins and phosphoproteins regulate diverse cellular processes. Biochem. J. 381: 329342.
79. Mahajan-Miklos, S.,, M. W. Tan,, L. G. Rahme, and, F. M. Ausubel. 1999. Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 96: 4756.
80. Maresso, A. W.,, M. R. Baldwin, and, J. T. Barbieri. 2004. Ezrin/radixin/moesin proteins are high affinity targets for ADP-ribosylation by Pseudomonas aeruginosa ExoS. J. Biol. Chem. 279: 3840238408.
81. Marklund, S. L. 1984. Extracellular superoxide dismutase and other superoxide dismutase isoenzymes in tissues from nine mammalian species. Biochem. J. 222: 649655.
82. Marklund, S. L. 1990. Expression of extracellular superoxide dismutase by human cell lines. Biochem. J. 266: 213219.
83. Masters, S. C.,, K. J. Pederson,, L. Zhang,, J. T. Barbieri, and, H. Fu. 1999. Interaction of 14-3-3 with a nonphosphorylated protein ligand, exoenzyme S of Pseudomonas aeruginosa. Biochemistry 38: 52165221.
84. Matsuda, M., and, T. Kurata. 1996. Emerging components of the Crk oncogene product: the first identified adaptor protein. Cell. Signal. 8: 335340.
85. Matsumoto, G.,, S. Kim, and, R. I. Morimoto. 2006. Huntingtin and mutant SOD1 form aggregate structures with distinct molecular properties in human cells. J. Biol. Chem. 281: 44774485.
86. Matsumoto, K. 2004. Role of bacterial proteases in pseudomonal and serratial keratitis. Biol. Chem. 385: 10071016.
87. McNamara, N. A.,, R. Van,, O. S. Tuchin, and, S. M. Fleiszig. 1999. Ocular surface epithelia express mRNA for human beta defensin-2. Exp. Eye Res. 69: 483490.
88. Miyata, S.,, M. Casey,, D. W. Frank,, F. M. Ausubel, and, E. Drenkard. 2003. Use of the Galleria mellonella caterpillar as a model host to study the role of the type III secretion system in Pseudomonas aeruginosa pathogenesis. Infect. Immun. 71: 24042413.
89. Mock, M.,, E. Labruyere,, P. Glaser,, A. Danchin, and, A. Ullmann. 1988. Cloning and expression of the calmodulin-sensitive Bacillus anthracis adenylate cyclase in Escherichia coli. Gene 64: 277284.
90. Mondola, P.,, M. Santillo,, R. Seru,, S. Damiano,, C. Alvino,, G. Ruggiero,, P. Formisano,, G. Terrazzano,, A. Secondo, and, L. Annunziato. 2004. Cu,Zn superoxide dismutase increases intracellular calcium levels via a phospholipase C-protein kinase C pathway in SK-N-BE neuroblastoma cells. Biochem. Biophys. Res. Commun. 324: 887892.
91. Mueller, C. A.,, P. Broz,, S. A. Muller,, P. Ringler,, F. Erne-Brand,, I. Sorg,, M. Kuhn,, A. Engel, and, G. R. Cornelis. 2005. The V-antigen of Yersinia forms a distinct structure at the tip of injectisome needles. Science 310: 674676.
92. Muslin, A. J.,, J. W. Tanner,, P. M. Allen, and, A. S. Shaw. 1996. Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. Cell 84: 889897.
93. Nalefski, E. A.,, L. A. Sultzman,, D. M. Martin,, R. W. Kriz,, P. S. Towler,, J. L. Knopf, and, J. D. Clark. 1994. Delineation of two functionally distinct domains of cytosolic phospholipase A2, a regulatory Ca(2+)-dependent lipid-binding domain and a Ca(2+)-independent catalytic domain. J. Biol. Chem. 269: 1823918249.
94. Ni, M.,, D. J. Evans,, S. Hawgood,, E. M. Anders,, R. A. Sack, and, S. M. Fleiszig. 2005. Surfactant protein D is present in human tear fluid and the cornea and inhibits epithelial cell invasion by Pseudomonas aeruginosa. Infect. Immun. 73: 21472156.
95. Nicas, T. I., and, B. H. Iglewski. 1984. Isolation and characterization of transposon-induced mutants of Pseudomonas aeruginosa deficient in production of exoenzyme S. Infect. Immun. 45: 470474.
96. Obritsch, M. D.,, D. N. Fish,, R. MacLaren, and, R. Jung. 2005. Nosocomial infections due to multidrug-resistant Pseudomonas aeruginosa: epidemiology and treatment options. Pharmacotherapy 25: 13531364.
97. Olson, J. C.,, J. E. Fraylick,, E. M. McGuffie,, K. M. Dolan,, T. L. Yahr,, D. W. Frank, and, T. S. Vincent. 1999. Interruption of multiple cellular processes in HT-29 epithelial cells by Pseudomonas aeruginosa exoenzyme S. Infect. Immun. 67: 28472854.
98. Olson, J. C.,, E. M. McGuffie, and, D. W. Frank. 1997. Effects of differential expression of the 49-kilodalton exoenzyme S by Pseudomonas aeruginosa on cultured eukaryotic cells. Infect. Immun. 65: 248256.
99. Pasinelli, P.,, M. E. Belford,, N. Lennon,, B. J. Bacskai,, B. T. Hyman,, D. Trotti, and, R. H. Brown, Jr. 2004. Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria. Neuron 43: 1930.
100. Pavlovskis, O. R.,, B. H. Iglewski, and, M. Pollack. 1978. Mechanism of action of Pseudomonas aeruginosa exotoxin A in experimental mouse infections: adenosine diphosphate ribosylation of elongation factor 2. Infect. Immun. 19: 2933.
101. Pavlovskis, O. R.,, M. Pollack,, L. T. Callahan III, and, B. H. Iglewski. 1977. Passive protection by antitoxin in experimental Pseudomonas aeruginosa burn infections. Infect. Immun. 18: 596602.
102. Pederson, K. J., and, J. T. Barbieri. 1998. Intra-cellular expression of the ADP-ribosyltransferase domain of Pseudomonas exoenzyme S is cytotoxic to eukaryotic cells. Mol. Microbiol. 30: 751759.
103. Pederson, K. J.,, A. J. Vallis,, K. Aktories,, D. W. Frank, and, J. T. Barbieri. 1999. The amino-terminal domain of Pseudomonas aeruginosa ExoS disrupts actin filaments via small-molecular-weight GTP-binding proteins. Mol. Microbiol. 32: 393401.
104. Phillips, R. M.,, D. A. Six,, E. A. Dennis, and, P. Ghosh. 2003. In vivo phospholipase activity of the Pseudomonas aeruginosa cytotoxin ExoU and protection of mammalian cells with phospholipase A(2) inhibitors. J. Biol. Chem. 278: 4132641332.
105. Pier, G. B. 1998. Pseudomonas aeruginosa: a key problem in cystic fibrosis. ASM News 64: 339347.
106. Pozuelo, R. M.,, K. M. Geraghty,, B. H. Wong,, N. T. Wood,, D. G. Campbell,, N. Morrice, and, C. Mackintosh. 2004. 14-3-3-affinity purification of over 200 human phosphoproteins reveals new links to regulation of cellular metabolism, proliferation and trafficking. Biochem. J. 379: 395408.
107. Pukatzki, S.,, R. H. Kessin, and, J. J. Mekalanos. 2002. The human pathogen Pseudomonas aeruginosa utilizes conserved virulence pathways to infect the social amoeba Dictyostelium discoideum. Proc. Natl. Acad. Sci. USA 99: 31593164.
108. Rabin, S. D., and, A. R. Hauser. 2005. Functional regions of the Pseudomonas aeruginosa cytotoxin ExoU. Infect. Immun. 73: 573582.
109. Rabin, S. D.,, J. L. Veesenmeyer,, K. T. Bieging, and, A. R. Hauser. 2006. A C-terminal domain targets the Pseudomonas aeruginosa cytotoxin ExoU to the plasma membrane of host cells. Infect. Immun. 74: 25522561.
110. Rabin, S. D. P., and, A. R. Hauser. 2003. Pseudomonas aeruginosa ExoU, a toxin transported by the type III secretion system, kills Saccharomyces cerevisiae. Infect. Immun. 71: 41444150.
111. Radke, J.,, K. J. Pederson, and, J. T. Barbieri. 1999. Pseudomonas aeruginosa exoenzyme S is a biglutamic acid ADP-ribosyltransferase. Infect. Immun. 67: 15081510.
112. Rasmussen, T. B., and, M. Givskov. 2006. Quorum sensing inhibitors: a bargain of effects. Microbiology 152: 895904.
113. Riese, M. J.,, A. Wittinghofer, and, J. T. Barbieri. 2001. ADP ribosylation of Arg41 of Rap by ExoS inhibits the ability of Rap to interact with its guanine nucleotide exchange factor, C3G. Biochemistry 40: 32893294.
114. Rocha, C. L.,, J. Coburn,, E. A. Rucks, and, J. C. Olson. 2003. Characterization of Pseudomonas aeruginosa exoenzyme S as a bifunctional enzyme in J774A.1 macrophages. Infect. Immun. 71: 52965305.
115. Roy-Burman, A.,, R. H. Savel,, S. Racine,, B. L. Swanson,, N. S. Revadigar,, J. Fujimoto,, T. Sawa,, D. W. Frank, and, J. P. WienerKronish. 2001. Type III protein secretion is associated with death in lower respiratory and systemic Pseudomonas aeruginosa infections. J. Infect. Dis. 183: 17671774.
116. Sadikot, R. T.,, T. S. Blackwell,, J. W. Christman, and, A. S. Prince. 2005. Pathogen-host interactions in Pseudomonas aeruginosa pneumonia. Am. J. Respir. Crit. Care Med. 171: 12091223.
117. Sato, H.,, J. B. Feix, and, D. W. Frank. 2006. Identification of superoxide dismutase as a cofactor for the Pseudomonas type III toxin, ExoU. Biochemistry 45: 1036810375.
118. Sato, H.,, J. B. Feix,, C. J. Hillard, and, D. W. Frank. 2005. Characterization of phospholipase activity of the Pseudomonas aeruginosa type III cytotoxin, ExoU. J. Bacteriol. 187: 11921195.
119. Sato, H., and, D. W. Frank. 2004. ExoU is a potent intracellular phospholipase. Mol. Microbiol. 53: 12791290.
120. Sato, H.,, D. W. Frank,, C. J. Hillard,, J. B. Feix,, R. R. Pankhaniya,, K. Moriyama,, V. Finck-Barbançon,, A. Buchaklian,, M. Lei,, R. M. Long,, J. Wiener-Kronish, and, T. Sawa. 2003. The mechanism of action of the Pseudomonas aeruginosa-encoded type III cytotoxin, ExoU. EMBO J. 22: 29592969.
121. Sawa, T.,, T. L. Yahr,, M. Ohara,, K. Kurahashi,, M. A. Gropper,, J. P. Wiener-Kronish, and, D. W. Frank. 1999. Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury. Nat. Med. 5: 392398.
122. Sayner, S. L.,, D. W. Frank,, J. King,, H. Chen,, J. VandeWaa, and, T. Stevens. 2004. Paradoxical cAMP-induced lung endothelial hyper-permeability revealed by Pseudomonas aeruginosa ExoY. Circ. Res. 95: 196203.
123. Shafikhani, S. H., and, J. Engel. 2006. Pseudomonas aeruginosa type III-secreted toxin ExoT inhibits host-cell division by targeting cytokinesis at multiple steps. Proc. Natl. Acad. Sci. USA 103: 1560515610.
124. Shinder, G. A.,, M. C. Lacourse,, S. Minotti, and, H. D. Durham. 2001. Mutant Cu/Zn-superoxide dismutase proteins have altered solubility and interact with heat shock/stress proteins in models of amyotrophic lateral sclerosis. J. Biol. Chem. 276: 1279112796.
125. Singh, P. K.,, M. R. Parsek,, E. P. Greenberg, and, M. J. Welsh. 2002. A component of innate immunity prevents bacterial biofilm development. Nature 417: 552555.
126. Singh, P. K.,, A. L. Schaefer,, M. R. Parsek,, T. O. Moninger,, M. J. Welsh, and, E. P. Greenberg. 2000. Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407: 762764.
127. Smith, R. S.,, E. R. Fedyk,, T. A. Springer,, N. Mukaida,, B. H. Iglewski, and, R. P. Phipps. 2001. IL-8 production in human lung fibroblasts and epithelial cells activated by the Pseudomonas autoinducer N-3-oxododecanoyl homoserine lactone is transcriptionally regulated by NF-kappa B and activator protein-2. J. Immunol. 167: 366374.
128. Smith, R. S.,, S. G. Harris,, R. Phipps, and, B. Iglewski. 2002. The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl) homoserine lactone contributes to virulence and induces inflammation in vivo. J. Bacteriol. 184: 11321139.
129. Smith, R. S.,, R. Kelly,, B. H. Iglewski, and, R. P. Phipps. 2002. The Pseudomonas autoinducer N-(3-oxododecanoyl) homoserine lactone induces cyclooxygenase-2 and prostaglandin E2 production in human lung fibroblasts: implications for inflammation. J. Immunol. 169: 26362642.
130. Stirling, F. R.,, A. Cuzick,, S. M. Kelly,, D. Oxley, and, T. J. Evans. 2006. Eukaryotic localization, activation and ubiquitinylation of a bacterial type III secreted toxin. Cell. Microbiol. 8: 12941309.
131. Stover, C. K.,, X. Q. Pham,, A. L. Erwin,, S. D. Mizoguchi,, P. Warrener,, M. J. Hickey,, F. S. Brinkman,, W. O. Hufnagle,, D. J. Kowalik,, M. Lagrou,, R. L. Garber,, L. Goltry,, E. Tolentino,, S. Westbrock-Wadman,, Y. Yuan,, L. L. Brody,, S. N. Coulter,, K. R. Folger,, A. Kas,, K. Larbig,, R. Lim,, K. Smith,, D. Spencer,, G. K. Wong,, Z. Wu,, I. T. Paulsen,, J. Reizer,, M. H. Saier,, R. E. Hancock,, S. Lory, and, M. V. Olson. 2000. Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 406: 959964.
132. Sun, J., and, J. T. Barbieri. 2003. Pseudomonas aeruginosa ExoT ADP-ribosylates CT10 regulator of kinase (Crk) proteins. J. Biol. Chem. 278: 3279432800.
133. Sun, J., and, J. T. Barbieri. 2004. ExoS Rho GTPase-activating protein activity stimulates reorganization of the actin cytoskeleton through Rho GTPase guanine nucleotide disassociation inhibitor. J. Biol. Chem. 279: 4293642944.
134. Tamura, M.,, T. Ajayi,, L. R. Allmond,, K. Moriyama,, J. P. Wiener-Kronish, and, T. Sawa. 2004. Lysophospholipase A activity of Pseudomonas aeruginosa type III secretory toxin ExoU. Biochem. Biophys. Res. Commun. 316: 323331.
135. Tan, M. W.,, S. Mahajan-Miklos, and, F. M. Ausubel. 1999. Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc. Natl. Acad. Sci. USA 96: 715720.
136. Tan, M. W.,, L. G. Rahme,, J. A. Sternberg,, R. G. Tompkins, and, F. M. Ausubel. 1999. Pseudomonas aeruginosa killing of Caenorhabditis elegans used to identify P. aeruginosa virulence factors. Proc. Natl. Acad. Sci. USA 96: 24082413.
137. Tateda, K.,, Y. Ishii,, M. Horikawa,, T. Matsumoto,, S. Miyairi,, J. C. Pechere,, T. J. Standiford,, M. Ishiguro, and, K. Yamaguchi. 2003. The Pseudomonas aeruginosa autoinducer N-3-oxododecanoyl homoserine lactone accelerates apoptosis in macrophages and neutrophils. Infect. Immun. 71: 57855793.
138. Taylor, G. D.,, M. Buchanan-Chell,, T. Kirkland,, M. McKenzie, and, R. Wiens. 1995. Bacteremic nosocomial pneumonia. A 7-year experience in one institution. Chest 108: 786788.
139. Telford, G.,, D. Wheeler,, P. Williams,, P. T. Tomkins,, P. Appleby,, H. Sewell,, G. S. Stewart,, B. W. Bycroft, and, D. I. Pritchard. 1998. The Pseudomonas aeruginosa quorum-sensing signal molecule N-(3-oxododecanoyl)- L-homoserine lactone has immunomodulatory activity. Infect. Immun. 66: 3642.
140. Troisfontaines, P., and, G. R. Cornelis. 2005. Type III secretion: more systems than you think. Physiology (Bethesda) 20: 326339.
141. Tsai, W. C.,, R. M. Strieter,, B. Mehrad,, M. W. Newstead,, X. Zeng, and, T. J. Standiford. 2000. CXC chemokine receptor CXCR2 is essential for protective innate host response in murine Pseudomonas aeruginosa pneumonia. Infect. Immun. 68: 42894296.
142. Vance, R. E.,, A. Rietsch, and, J. J. Mekalanos. 2005. Role of the type III secreted exoenzymes S, T, and Y in systemic spread of Pseudomonas aeruginosa PAO1 in vivo. Infect. Immun. 73: 17061713.
143. van Tilbeurgh, H.,, S. Bezzine,, C. Cambillau,, R. Verger, and, F. Carriere. 1999. Colipase: structure and interaction with pancreatic lipase. Biochim. Biophys. Acta 1441: 173184.
144. Vasil, M. L., and, U. A. Ochsner. 1999. The response of Pseudomonas aeruginosa to iron: genetics, biochemistry and virulence. Mol. Microbiol. 34: 399413.
145. Ventre, I.,, A. L. Goodman,, I. Vallet-Gely,, P. Vasseur,, C. Soscia,, S. Molin,, S. Bleves,, A. Lazdunski,, S. Lory, and, A. Filloux. 2006. Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes. Proc. Natl. Acad. Sci. USA 103: 171176.
146. Vincent, T. S.,, J. E. Fraylick,, E. M. McGuffie, and, J. C. Olson. 1999. ADP-ribosylation of oncogenic Ras proteins by Pseudomonas aeruginosa exoenzyme S in vivo. Mol. Microbiol. 32: 10541064.
147. Wagner, V. E.,, D. Bushnell,, L. Passador,, A. I. Brooks, and, B. H. Iglewski. 2003. Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment. J. Bacteriol. 185: 20802095.
148. Weisiger, R. A., and, I. Fridovich. 1973. Mitochondrial superoxide simutase. Site of synthesis and intramitochondrial localization. J. Biol. Chem. 248: 47934796.
149. Whiteley, M.,, M. G. Bangera,, R. E. Bumgarner,, M. R. Parsek,, G. M. Teitzel,, S. Lory, and, E. P. Greenberg. 2001. Gene expression in Pseudomonas aeruginosa biofilms. Nature 413: 860864.
150. Wispe, J. R.,, B. B. Warner,, J. C. Clark,, C. R. Dey,, J. Neuman,, S. W. Glasser,, J. D. Crapo,, L. Y. Chang, and, J. A. Whitsett. 1992. Human Mn-superoxide dismutase in pulmonary epithelial cells of transgenic mice confers protection from oxygen injury. J. Biol. Chem. 267: 2393723941.
151. Wong, G. H.,, J. H. Elwell,, L. W. Oberley, and, D. V. Goeddel. 1989. Manganous super-oxide dismutase is essential for cellular resistance to cytotoxicity of tumor necrosis factor. Cell 58: 923931.
152. Wright, J. R. 2005. Immunoregulatory functions of surfactant proteins. Nat. Rev. Immunol. 5: 5868.
153. Wurtele, M.,, L. Renault,, J. T. Barbieri,, A. Wittinghofer, and, E. Wolf. 2001. Structure of the ExoS GTPase activating domain. FEBS Lett. 491: 2629.
154. Yaffe, M. B.,, K. Rittinger,, S. Volinia,, P. R. Caron,, A. Aitken,, H. Leffers,, S. J. Gamblin,, S. J. Smerdon, and, L. C. Cantley. 1997. The structural basis for 14-3-3:phosphopeptide binding specificity. Cell 91: 961971.
155. Yahr, T. L.,, J. T. Barbieri, and, D. W. Frank. 1996. Genetic relationship between the 53- and 49-kilodalton forms of exoenzyme S from Pseudomonas aeruginosa. J. Bacteriol. 178: 14121419.
156. Yahr, T. L.,, J. Goranson, and, D. W. Frank. 1996. Exoenzyme S of Pseudomonas aeruginosa is secreted by a type III pathway. Mol. Microbiol. 22: 9911003.
157. Yahr, T. L.,, L. M. Mende-Mueller,, M. B. Friese, and, D. W. Frank. 1997. Identification of type III secreted products of the Pseudomonas aeruginosa exoenzyme S regulon. J. Bacteriol. 179: 71657168.
158. Yahr, T. L.,, A. J. Vallis,, M. K. Hancock,, J. T. Barbieri, and, D. W. Frank. 1998. ExoY, an adenylate cyclase secreted by the Pseudomonas aeruginosa type III system. Proc. Natl. Acad. Sci. USA 95: 1389913904.
159. Yahr, T. L., and, M. C. Wolfgang. 2006. Transcriptional regulation of the Pseudomonas aeruginosa type III secretion system. Mol. Microbiol. 62: 631640.
160. Yip, C. K., and, N. C. Strynadka. 2006. New structural insights into the bacterial type III secretion system. Trends Biochem. Sci. 31: 223230.
161. Zaborina, O.,, J. E. Kohler,, Y. Wang,, C. Bethel,, O. Shevchenko,, L. Wu,, J. R. Turner, and, J. C. Alverdy. 2006. Identification of multi-drug resistant Pseudomonas aeruginosa clinical isolates that are highly disruptive to the intestinal epithelial barrier. Ann. Clin. Microbiol. Antimicrob. 5: 14.
162. Zhang, L.,, H. Wang,, D. Liu,, R. Liddington, and, H. Fu. 1997. Raf-1 kinase and exoenzyme S interact with 14-3-3zeta through a common site involving lysine 49. J. Biol. Chem. 272: 1371713724.
163. Zhang, Y., and, J. T. Barbieri. 2005. A leucine-rich motif targets Pseudomonas aeruginosa ExoS within mammalian cells. Infect. Immun. 73: 79387945.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error