Chapter 16 : Interaction of with Host Cells

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

Preview this chapter:
Zoom in

Interaction of with Host Cells, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815554/9781555814373_Chap16-1.gif /docserver/preview/fulltext/10.1128/9781555815554/9781555814373_Chap16-2.gif


This chapter discuss three critical aspects of the interaction of with host cells: (i) its ability to mediate its own uptake into nonphagocytic cells, (ii) its ability to modulate vesicular trafficking pathways to avoid delivery into lysosomes, and (iii) its ability to reprogram host cell gene expression to stimulate the production of proinflammatory cytokines. The strong phenotype associated with capsular mutants in different animal models is likely to be due to reasons other than their rather minor effect in bacterial internalization. Therefore, it is likely that the capsular polysaccharide may contribute to internalization indirectly, perhaps by promoting bacterial attachment to host cells. Bacterial internalization does not require dynamin, an essential component of the endocytic machinery associated with cavaealoe. Like other intracellular pathogens, must have evolved specific adaptations to survive within host cells. Intestinal epithelial cells are equipped to mount innate immune responses upon detection of microbial pathogens. The last few years have seen advances in the understanding of the cell biology of infection, although more studies will be required to gain an understanding of these issues on par with that of other pathogenic bacteria. Although many mutants apparently defective in some of these process have been identified (e.g., bacterial entry), the direct involvement of these determinants in – host cell interactions has not been demonstrated. The availability of powerful genetic tools, coupled with a better understanding of the cell biology of infection, can help to identify those bacterial determinants.

Citation: Watson R, Galán J. 2008. Interaction of with Host Cells, p 289-296. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch16
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1.
Figure 1.

Model for internalization and trafficking within epithelial cells. enters intestinal epithelial cell via a microtubule and caveolae-dependent process. After internalization, the CCV transiently acquires different markers of the endocytic pathway and ultimately survives within a compartment that is functionally separated from the canonical endocytic pathway. Adapted from .

Citation: Watson R, Galán J. 2008. Interaction of with Host Cells, p 289-296. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Alexander, J.,, A. R. Satoskar, and, D. G. Russell. 1999. Leishmania species: models of intracellular parasitism. J. Cell. Sci. 112 (Pt. 18): 29933002.
2. Andersen-Nissen, E.,, K. D. Smith,, K. L. Strobe,, S. L. Barrett,, B. T. Cookson,, S. M. Logan, and, A. Aderem. 2005. Evasion of Toll-like receptor 5 by flagellated bacteria. Proc. Natl. Acad. Sci. USA 102: 92479252.
3. Babakhani, F. K., and, L. A. Joens. 1993. Primary swine intestinal cells as a model for studying Campylobacter jejuni invasiveness. Infect. Immun. 61: 27232726.
4. Bachtiar, B. M.,, P. J. Coloe, and, B. N. Fry. 2007. Knockout mutagenesis of the kpsE gene of Campylobacter jejuni 81116 and its involvement in bacterium-host interactions. FEMS Immunol. Med. Microbiol. 49: 149154.
5. Bacon, D. J.,, C. M. Szymanski,, D. H. Burr,, R. P. Silver,, R. A. Alm, and, P. Guerry. 2001. A phase-variable capsule is involved in virulence of Campylobacter jejuni 81-176. Mol. Microbiol. 40: 769777.
6. Bakhiet, M.,, F. S. Al-Salloom,, A. Qareiballa,, K. Bindayna,, I. Farid, and, G. A. Botta. 2004. Induction of alpha and beta chemokines by intestinal epithelial cells stimulated with Campylobacter jejuni. J. Infect. 48: 236244.
7. Banfi, E.,, M. Cinco, and, G. Zabucchi. 1986. Phagocytosis of Campylobacter jejuni and C. coli by peritoneal macrophages. J. Gen. Microbiol. 132: 24092412.
8. Biswas, D.,, K. Itoh, and, C. Sasakawa. 2000. Uptake pathways of clinical and healthy animal isolates of Campylobacter jejuni into INT-407 cells. FEMS Immunol. Med. Microbiol. 29: 203211.
9. Biswas, D.,, K. Itoh, and, C. Sasakawa. 2003. Role of microfilaments and microtubules in the invasion of INT-407 cells by Campylobacter jejuni. Microbiol. Immunol. 47: 469473.
10. Biswas, D.,, H. Niwa, and, K. Itoh. 2004. Infection with Campylobacter jejuni induces tyrosine-phosphorylated proteins into INT-407 cells. Microbiol. Immunol. 48: 221228.
11. Brener, Z. 1973. Biology of Trypanosoma cruzi. Annu. Rev. Microbiol. 27: 347382.
12. Candon, H. L.,, B. J. Allan,, C. D. Fraley, and, E. C. Gaynor. 2007. Polyphosphate kinase 1 (PPK1) is a pathogenesis determinant in Campylobacter jejuni. J. Bacteriol. 189: 80998108.
13. Carrillo, C. D.,, E. Taboada,, J. H. Nash,, P. Lanthier,, J. Kelly,, P. C. Lau,, R. Verhulp,, O. Mykytczuk,, J. Sy,, W. A. Findlay,, K. Amoako,, S. Gomis,, P. Willson,, J. W. Austin,, A. Potter,, L. Babiuk,, B. Allan, and, C. M. Szymanski. 2004. Genome-wide expression analyses of Campylobacter jejuni NCTC11168 reveals coordinate regulation of motility and virulence by flhA. J. Biol. Chem. 279: 2032720338.
14. Chen, M. L.,, Z. Ge,, J. G. Fox, and, D. B. Schauer. 2006. Disruption of tight junctions and induction of proinflammatory cytokine responses in colonic epithelial cells by Campylobacter jejuni. Infect. Immun. 74: 65816589.
15. Clerc, P., and, P. J. Sansonetti. 1987. Entry of Shigella flexneri into HeLa cells: evidence for directed phagocytosis involving actin polymerization and myosin accumulation. Infect. Immun. 55: 26812688.
16. Cossart, P., and, P. J. Sansonetti. 2004. Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 304: 242248.
17. Dann, S. M., and, L. Eckmann. 2007. Innate immune defenses in the intestinal tract. Curr. Opin. Gastroenterol. 23: 115120.
18. Day, W. A., Jr.,, J. L. Sajecki,, T. M. Pitts, and, L. A. Joens. 2000. Role of catalase in Campylobacter jejuni intracellular survival. Infect. Immun. 68: 63376345.
19. De Melo, M. A.,, G. Gabbiani, and, J. C. Pechere. 1989. Cellular events and intracellular survival of Campylobacter jejuni during infection of HEp-2 cells. Infect. Immun. 57: 22142222.
20. Deretic, V.,, S. Singh,, S. Master,, J. Harris,, E. Roberts,, G. Kyei,, A. Davis,, S. de Haro,, J. Naylor,, H. H. Lee, and, I. Vergne. 2006. Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism. Cell. Microbiol. 8: 719727.
21. Dramsi, S., and, P. Cossart. 1998. Intracellular pathogens and the actin cytoskeleton. Annu. Rev. Cell. Dev. Biol. 14: 137166.
22. Finlay, B. B.,, S. Ruschkowski, and, S. Dedhar. 1991. Cytoskeletal rearrangements accompanying salmonella entry into epithelial cells. J. Cell. Sci. 99 (Pt. 2): 283296.
23. Fouts, D. E.,, E. F. Mongodin,, R. E. Mandrell,, W. G. Miller,, D. A. Rasko,, J. Ravel,, L. M. Brinkac,, R. T. DeBoy,, C. T. Parker,, S. C. Daugherty,, R. J. Dodson,, A. S. Durkin,, R. Madupu,, S. A. Sullivan,, J. U. Shetty,, M. A. Ayodeji,, A. Shvartsbeyn,, M. C. Schatz,, J. H. Badger,, C. M. Fraser, and, K. E. Nelson. 2005. Major structural differences and novel potential virulence mechanisms from the genomes of multiple Campylobacter species. PLoS Biol. 3: e15.
24. Fritz, J. H.,, R. L. Ferrero,, D. J. Philpott, and, S. E. Girardin. 2006. Nod-like proteins in immunity, inflammation and disease. Nat. Immunol. 7: 12501257.
25. Gaillard, J. L.,, P. Berche,, J. Mounier,, S. Richard, and, P. Sansonetti. 1987. In vitro model of penetration and intracellular growth of Listeria monocytogenes in the human enterocyte-like cell line Caco-2. Infect. Immun. 55: 28222829.
26. Galan, J. E.,, C. Ginocchio, and, P. Costeas. 1992. Molecular and functional characterization of the Salmonella invasion gene invA: homology of InvA to members of a new protein family. J. Bacteriol. 174: 43384349.
27. Garcia-del Portillo, F., and, B. B. Finlay. 1995. Targeting of Salmonella typhimurium to vesicles containing lysosomal membrane glycoproteins bypasses compartments with mannose 6-phosphate receptors. J. Cell Biol. 129: 8197.
28. Goebel, W., and, M. Kuhn. 2000. Bacterial replication in the host cell cytosol. Curr. Opin. Microbiol. 3: 4953.
29. Golden, N. J., and, D. W. Acheson. 2002. Identification of motility and autoagglutination Campylobacter jejuni mutants by random transposon mutagenesis. Infect. Immun. 70: 17611771.
30. Grant, C. C.,, M. E. Konkel,, W. Cieplak, Jr., and, L. S. Tompkins. 1993. Role of flagella in adherence, internalization, and translocation of Campylobacter jejuni in nonpolarized and polarized epithelial cell cultures. Infect. Immun. 61: 17641771.
31. Guerry, P.,, C. P. Ewing,, M. Schirm,, M. Lorenzo,, J. Kelly,, D. Pattarini,, G. Majam,, P. Thibault, and, S. Logan. 2006. Changes in flagellin glycosylation affect Campylobacter autoagglutination and virulence. Mol. Microbiol. 60: 299311.
32. Henley, J. R.,, E. W. Krueger,, B. J. Oswald, and, M. A. McNiven. 1998. Dynamin-mediated internalization of caveolae. J. Cell Biol. 141: 8599.
33. Hickey, T. E.,, A. L. McVeigh,, D. A. Scott,, R. E. Michielutti,, A. Bixby,, S. A. Carroll,, A. L. Bourgeois, and, P. Guerry. 2000. Campylobacter jejuni cytolethal distending toxin mediates release of interleukin-8 from intestinal epithelial cells. Infect. Immun. 68: 65356541.
34. Hofreuter, D.,, J. Tsai,, R. O. Watson,, V. Novik,, B. Altman,, M. Benitez,, C. Clark,, C. Perbost,, T. Jarvie,, L. Du, and, J. E. Galan. 2006. Unique features of a highly pathogenic Campylobacter jejuni strain. Infect. Immun. 74: 46944707.
35. Hu, L., and, D. J. Kopecko. 1999. Campylobacter jejuni 81-176 associates with microtubules and dynein during invasion of human intestinal cells. Infect. Immun. 67: 41714182.
36. Hu, L., and, T. E. Hickey. 2005. Campylobacter jejuni induces secretion of proinflammatory chemokines from human intestinal epithelial cells. Infect. Immun. 73: 44374440.
37. Hu, L.,, J. P. McDaniel, and, D. J. Kopecko. 2006. Signal transduction events involved in human epithelial cell invasion by Campylobacter jejuni 81-176. Microb. Pathog. 40: 91100.
38. Hu, L.,, R. B. Raybourne, and, D. J. Kopecko. 2005. Ca 2+ release from host intracellular stores and related signal transduction during Campylobacter jejuni 81-176 internalization into human intestinal cells. Microbiology 151: 30973105.
39. Johanesen, P. A., and, M. B. Dwinell. 2006. Flagellin-independent regulation of chemokine host defense in Campylobacter jejuni–infected intestinal epithelium. Infect. Immun. 74: 34373447.
40. Jones, M. A.,, K. L. Marston,, C. A. Woodall,, D. J. Maskell,, D. Linton,, A. V. Karlyshev,, N. Dorrell,, B. W. Wren, and, P. A. Barrow. 2004. Adaptation of Campylobacter jejuni NCTC11168 to high-level colonization of the avian gastrointestinal tract. Infect. Immun. 72: 37693776.
41. Jones, M. A.,, S. Totemeyer,, D. J. Maskell,, C. E. Bryant, and, P. A. Barrow. 2003. Induction of proinflammatory responses in the human monocytic cell line THP-1 by Campylobacter jejuni. Infect. Immun. 71: 26262633.
42. Kakuda, T., and, V. J. DiRita. 2006. Cj1496c encodes a Campylobacter jejuni glycoprotein that influences invasion of human epithelial cells and colonization of the chick gastrointestinal tract. Infect. Immun. 74: 47154723.
43. Karlyshev, A. V.,, P. Everest,, D. Linton,, S. Cawthraw,, D. G. Newell, and, B. W. Wren. 2004. The Campylobacter jejuni general glycosylation system is important for attachment to human epithelial cells and in the colonization of chicks. Microbiology 150: 19571964.
44. Ketley, J. M. 1997. Pathogenesis of enteric infection by Campylobacter. Microbiology 143 (Pt. 1): 521.
45. Kiehlbauch, J. A.,, R. A. Albach,, L. L. Baum, and, K. P. Chang. 1985. Phagocytosis of Campylobacter jejuni and its intracellular survival in mononuclear phagocytes. Infect. Immun. 48: 446451.
46. Knodler, L. A., and, O. Steele-Mortimer. 2003. Taking possession: biogenesis of the Salmonella-containing vacuole. Traffic 4: 587599.
47. Konkel, M. E.,, S. F. Hayes,, L. A. Joens, and, W. Cieplak, Jr. 1992. Characteristics of the internalization and intracellular survival of Campylobacter jejuni in human epithelial cell cultures. Microb. Pathog. 13: 357370.
48. Konkel, M. E., and, L. A. Joens. 1989. Adhesion to and invasion of HEp-2 cells by Campylobacter spp. Infect. Immun. 57: 29842990.
49. Konkel, M. E.,, J. D. Klena,, V. Rivera-Amill,, M. R. Monteville,, D. Biswas,, B. Raphael, and, J. Mickelson. 2004. Secretion of virulence proteins from Campylobacter jejuni is dependent on a functional flagellar export apparatus. J. Bacteriol. 186: 32963303.
50. Krause-Gruszczynska, M.,, M. Rohde,, R. Hartig,, H. Genth,, G. Schmidt,, T. Keo,, W. Konig,, W. G. Miller,, M. E. Konkel, and, S. Backert. 2007. Role of the small Rho GTPases Rac1 and Cdc42 in host cell invasion of Campylobacter jejuni. Cell. Microbiol. 9: 24312444.
51. Kuhn, M.,, M. C. Prevost,, J. Mounier, and, P. J. Sansonetti. 1990. A nonvirulent mutant of Listeria monocytogenes does not move intracellularly but still induces polymerization of actin. Infect. Immun. 58: 34773486.
52. Lara-Tejero, M., and, J. E. Galan. 2000. A bacterial toxin that controls cell cycle progression as a deoxyribonuclease I–like protein. Science 290: 354357.
53. Medzhitov, R. 2001. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1: 135145.
54. Mellits, K. H.,, J. Mullen,, M. Wand,, G. Armbruster,, A. Patel,, P. L. Connerton,, M. Skelly, and, I. F. Connerton. 2002. Activation of the transcription factor NF-kappaB by Campylobacter jejuni. Microbiology 148: 27532763.
55. Meresse, S.,, O. Steele-Mortimer,, B. B. Finlay, and, J. P. Gorvel. 1999. The rab7 GTPase controls the maturation of Salmonella typhimurium–containing vacuoles in HeLa cells. EMBO J. 18: 43944403.
56. Meylan, E.,, J. Tschopp, and, M. Karin. 2006. Intracellular pattern recognition receptors in the host response. Nature 442: 3944.
57. Monteville, M. R.,, J. E. Yoon, and, M. E. Konkel. 2003. Maximal adherence and invasion of INT 407 cells by Campylobacter jejuni requires the CadF outer-membrane protein and microfilament reorganization. Microbiology 149: 153165.
58. Myszewski, M. A., and, N. J. Stern. 1991. Phagocytosis and intra-cellular killing of Campylobacter jejuni by elicited chicken peritoneal macrophages. Avian Dis. 35: 750755.
59. Naess, V.,, C. Johannessen, and, T. Hofstad. 1988. Adherence of Campylobacter jejuni and Campylobacter coli to porcine intestinal brush border membranes. APMIS 96: 681687.
60. Naikare, H.,, K. Palyada,, R. Panciera,, D. Marlow, and, A. Stintzi. 2006. Major role for FeoB in Campylobacter jejuni ferrous iron acquisition, gut colonization, and intracellular survival. Infect. Immun. 74: 54335444.
61. Newell, D. G.,, H. McBride, and, J. M. Dolby. 1985. Investigations on the role of flagella in the colonization of infant mice with Campylobacter jejuni and attachment of Campylobacter jejuni to human epithelial cell lines. J. Hyg. (Lond.) 95: 217227.
62. Newell, D. G., and, A. Pearson. 1984. The invasion of epithelial cell lines and the intestinal epithelium of infant mice by Campylobacter jejuni/ coli. J. Diarrhoeal Dis. Res. 2: 1926.
63. Oelschlaeger, T. A.,, P. Guerry, and, D. J. Kopecko. 1993. Unusual microtubule-dependent endocytosis mechanisms triggered by Campylobacter jejuni and Citrobacter freundii. Proc. Natl. Acad. Sci. USA 90: 68846888.
64. Ogawa, M., and, C. Sasakawa. 2006. Intracellular survival of Shigella. Cell. Microbiol. 8: 177184.
65. Oh, P.,, D. P. McIntosh, and, J. E. Schnitzer. 1998. Dynamin at the neck of caveolae mediates their budding to form transport vesicles by GTP-driven fission from the plasma membrane of endothelium. J. Cell. Biol. 141: 101114.
66. Parkhill, J.,, B. W. Wren,, K. Mungall,, J. M. Ketley,, C. Churcher,, D. Basham,, T. Chillingworth,, R. M. Davies,, T. Feltwell,, S. Holroyd,, K. Jagels,, A. V. Karlyshev,, S. Moule,, M. J. Pallen,, C. W. Penn,, M. A. Quail,, M. A. Rajandream,, K. M. Rutherford,, A. H. van Vliet,, S. Whitehead, and, B. G. Barrell. 2000. The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 403: 665668.
67. Poly, F.,, T. Read,, D. R. Tribble,, S. Baqar,, M. Lorenzo, and, P. Guerry. 2007. Genome sequence of a clinical isolate of Campylobacter jejuni from Thailand. Infect. Immun. 75: 34253433.
68. Rinella, E. S.,, C. D. Eversley,, I. M. Carroll,, J. M. Andrus,, D. W. Threadgill, and, D. S. Threadgill. 2006. Human epithelialspecific response to pathogenic Campylobacter jejuni. FEMS Microbiol. Lett. 262: 236243.
69. Rivera-Amill, V.,, B. J. Kim,, J. Seshu, and, M. E. Konkel. 2001. Secretion of the virulence-associated Campylobacter invasion antigens from Campylobacter jejuni requires a stimulatory signal. J. Infect. Dis. 183: 16071616.
70. Russell, R., and, D. J. Blake. 1994. Cell association and invasion of Caco-2 cells by Campylobacter jejuni. Infect. Immun. 62: 37733779.
71. Russell, R. G.,, M. O’Donnoghue,, D. C. Blake, Jr.,, J. Zulty, and, L. J. DeTolla. 1993. Early colonic damage and invasion of Campylobacter jejuni in experimentally challenged infant Macaca mulatta. J. Infect. Dis. 168: 210215.
72. Simons, K., and, D. Toomre. 2000. Lipid rafts and signal transduction. Nat. Rev. Mol. Cell. Biol. 1: 3139.
73. Song, Y. C.,, S. Jin,, H. Louie,, D. Ng,, R. Lau,, Y. Zhang,, R. Weerasekera,, S. Al Rashid,, L. A. Ward,, S. D. Der, and, V. L. Chan. 2004. FlaC, a protein of Campylobacter jejuni TGH9011 (ATCC43431) secreted through the flagellar apparatus, binds epithelial cells and influences cell invasion. Mol. Microbiol. 53: 541553.
74. Stephen, J. 2001. Pathogenesis of infectious diarrhea. Can. J. Gastroenterol. 15: 669683.
75. Szymanski, C. M.,, D. H. Burr, and, P. Guerry. 2002. Campylobacter protein glycosylation affects host cell interactions. Infect. Immun. 70: 22422244.
76. Takei, K.,, P. S. McPherson,, S. L. Schmid, and, P. De Camilli. 1995. Tubular membrane invaginations coated by dynamin rings are induced by GTP-gamma S in nerve terminals. Nature 374: 186190.
77. van Spreeuwel, J. P.,, G. C. Duursma,, C. J. Meijer,, R. Bax,, P. C. Rosekrans, and, J. Lindeman. 1985. Campylobacter colitis: histological immunohistochemical and ultrastructural findings. Gut 26: 945951.
78. Vijayakumar, S.,, A. Merkx-Jacques,, D. B. Ratnayake,, I. Gryski,, R. K. Obhi,, S. Houle,, C. M. Dozois, and, C. Creuzenet. 2006. Cj1121c, a novel UDP-4-keto-6-deoxy-GlcNAc C-4 aminotransferase essential for protein glycosylation and virulence in Campylobacter jejuni. J. Biol. Chem. 281: 2773327743.
79. Wassenaar, T. M.,, N. M. Bleumink-Pluym, and, B. A. van der Zeijst. 1991. Inactivation of Campylobacter jejuni flagellin genes by homologous recombination demonstrates that flaA but not flaB is required for invasion. EMBO J. 10: 20552061.
80. Wassenaar, T. M.,, M. Engelskirchen,, S. Park, and, A. Lastovica. 1997. Differential uptake and killing potential of Campylobacter jejuni by human peripheral monocytes/macrophages. Med. Microbiol. Immunol. 186: 139144.
81. Watson, R. O., and, J. E. Galan. 2005. Signal transduction in Campylobacter jejuni–induced cytokine production. Cell. Microbiol. 7: 655665.
82. Watson, R. O., and, J. E. Galan. 2008. C. jejuni survives within epithelial cells by avoiding delivery to lysosomes. PloS Pathog. 4: 6983.
83. Watson, R. O.,, V. Novik,, D. Hofreuter,, M. Lara-Tejero, and, J. E. Galan. 2007. A MyD88-deficient mouse model reveals a role for Nramp1 in Campylobacter jejuni infection. Infect. Immun. 75: 19942003.
84. Whitehouse, C. A.,, P. B. Balbo,, E. C. Pesci,, D. L. Cottle,, P. M. Mirabito, and, C. L. Pickett. 1998. Campylobacter jejuni cyto-lethal distending toxin causes a G2-phase cell cycle block. Infect. Immun. 66: 19341940.
85. Wooldridge, K. G.,, P. H. Williams, and, J. M. Ketley. 1996. Host signal transduction and endocytosis of Campylobacter jejuni. Microb. Pathog. 21: 299305.
86. Yao, R.,, D. H. Burr,, P. Doig,, T. J. Trust,, H. Niu, and, P. Guerry. 1994. Isolation of motile and non-motile insertional mutants of Campylobacter jejuni: the role of motility in adherence and invasion of eukaryotic cells. Mol. Microbiol. 14: 883893.
87. Yao, R.,, D. H. Burr, and, P. Guerry. 1997. CheY-mediated modulation of Campylobacter jejuni virulence. Mol. Microbiol. 23: 10211031.
88. Zilbauer, M.,, N. Dorrell,, A. Elmi,, K. J. Lindley,, S. Schuller,, H. E. Jones,, N. J. Klein,, G. Nunez,, B. W. Wren, and, M. Bajaj-Elliott. 2007. A major role for intestinal epithelial nucleotide oligomerization domain 1 (NOD1) in eliciting host bactericidal immune responses to Campylobacter jejuni. Cell. Microbiol. 9: 2541.

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