Intra-Subtype Variation in Enteroadhesion Accounts for Differences in Epithelial Barrier Disruption and Is Associated with Metronidazole Resistance in Blastocystis Subtype-7

PLoS Neglected Tropical Diseases

Volumn 8, Issue 5, 2014, Pages

  Wu, Zhaona ^a   Mirza, Haris ^b   Tan, Kevin Shyong Wei ^a  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

METRONIDAZOLE; ANTIPROTOZOAL AGENT;

ANIMAL CELL; ARTICLE; CELL ADHESION; CELL DISRUPTION; CELL MEMBRANE PERMEABILITY; CELL PROLIFERATION; CELL VIABILITY; CONFOCAL LASER MICROSCOPY; CONTROLLED STUDY; CYTOPATHOGENIC EFFECT; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE; INTESTINE EPITHELIUM; INTRASPECIFIC VARIATION; NONHUMAN; PARASITE VIABILITY; PARASITE VIRULENCE; SPECIES DIFFERENCE; WESTERN BLOTTING; BLASTOCYSTIS; CACO 2 CELL LINE; DRUG EFFECTS; DRUG RESISTANCE; HOST PATHOGEN INTERACTION; METABOLISM; PATHOGENICITY; PHYSIOLOGY; TIGHT JUNCTION;

ANTIPROTOZOAL AGENTS; BLASTOCYSTIS; CACO-2 CELLS; CELL ADHESION; CELL MEMBRANE PERMEABILITY; CELL PROLIFERATION; DRUG RESISTANCE; HOST-PATHOGEN INTERACTIONS; HUMANS; METRONIDAZOLE; TIGHT JUNCTIONS;

EID: 84901757303     PISSN: 19352727     EISSN: 19352735     Source Type: Journal    
DOI: 10.1371/journal.pntd.0002885     Document Type: Article

References (111)

1. Scanlan PD, (2012) Blastocystis: past pitfalls and future perspectives. Trends Parasitol 28: 327-334.
2. Tan KS, (2008) New insights on classification, identification, and clinical relevance of Blastocystis spp. Clin Microbiol Rev 21: 639-665.
3. Tan KS, Mirza H, Teo JD, Wu B, Macary PA, (2010) Current Views on the Clinical Relevance of Blastocystis spp. Curr Infect Dis Rep 12: 28-35.
4. Poirier P, Wawrzyniak I, Vivares CP, Delbac F, El Alaoui H, (2012) New insights into Blastocystis spp.: a potential link with irritable bowel syndrome. PLoS Pathog 8: e1002545.
5. Alfellani MA, Taner-Mulla D, Jacob AS, Imeede CA, Yoshikawa H, et al. (2013) Genetic diversity of blastocystis in livestock and zoo animals. Protist 164: 497-509.
6. Kulik RA, Falavigna DL, Nishi L, Araujo SM, (2008) Blastocystis sp. and other intestinal parasites in hemodialysis patients. Braz J Infect Dis 12: 338-341.
7. Parkar U, Traub RJ, Kumar S, Mungthin M, Vitali S, et al. (2007) Direct characterization of Blastocystis from faeces by PCR and evidence of zoonotic potential. Parasitology 134: 359-367.
8. Puthia MK, Sio SW, Lu J, Tan KS, (2006) Blastocystis ratti induces contact-independent apoptosis, F-actin rearrangement, and barrier function disruption in IEC-6 cells. Infect Immun 74: 4114-4123.
9. Stenzel DJ, Boreham PF, (1996) Blastocystis hominis revisited. Clin Microbiol Rev 9: 563-584.
10. Tan KS, (2004) Blastocystis in humans and animals: new insights using modern methodologies. Vet Parasitol 126: 121-144.
11. Jimenez-Gonzalez DE, Martinez-Flores WA, Reyes-Gordillo J, Ramirez-Miranda ME, Arroyo-Escalante S, et al. (2012) Blastocystis infection is associated with irritable bowel syndrome in a Mexican patient population. Parasitol Res 110: 1269-1275.
12. Pasqui AL, Savini E, Saletti M, Guzzo C, Puccetti L, et al. (2004) Chronic urticaria and blastocystis hominis infection: a case report. Eur Rev Med Pharmacol Sci 8: 117-120.
13. Stark D, van Hal S, Marriott D, Ellis J, Harkness J, (2007) Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis. Int J Parasitol 37: 11-20.
14. Vogelberg C, Stensvold CR, Monecke S, Ditzen A, Stopsack K, et al. (2010) Blastocystis sp. subtype 2 detection during recurrence of gastrointestinal and urticarial symptoms. Parasitol Int 59: 469-471.
15. Garavelli PL, Orsi P, Scaglione L, (1988) Blastocystis hominis infection during AIDS. Lancet 2: 1364.
16. Kurniawan A, Karyadi T, Dwintasari SW, Sari IP, Yunihastuti E, et al. (2009) Intestinal parasitic infections in HIV/AIDS patients presenting with diarrhoea in Jakarta, Indonesia. Trans R Soc Trop Med Hyg 103: 892-898.
17. Llibre JM, Tor J, Manterola JM, Carbonell C, Foz M, (1989) Blastocystis hominis chronic diarrhoea in AIDS patients. Lancet 1: 221.
18. Tasova Y, Sahin B, Koltas S, Paydas S, (2000) Clinical significance and frequency of Blastocystis hominis in Turkish patients with hematological malignancy. Acta Med Okayama 54: 133-136.
19. Alexeieff A, (1911) Sur la nature des formations dites "Kystes de Trichomonas intestinalis". C R Soc Biol 71: 296-298.
20. Brumpt E, (1912) Blastocystis hominis n sp. et formes voisines. Bull Soc Pathol Exot 5: 725-730.
21. Clark CG, van der Giezen M, Alfellani MA, Stensvold CR, (2013) Recent developments in Blastocystis research. Adv Parasitol 82: 1-32.
22. Eroglu F, Genc A, Elgun G, Koltas IS, (2009) Identification of Blastocystis hominis isolates from asymptomatic and symptomatic patients by PCR. Parasitol Res 105: 1589-1592.
23. Kaneda Y, Horiki N, Cheng X, Tachibana H, Tsutsumi Y, (2000) Serologic response to Blastocystis hominis infection in asymptomatic individuals. Tokai J Exp Clin Med 25: 51-56.
24. Stensvold CR, Lewis HC, Hammerum AM, Porsbo LJ, Nielsen SS, et al. (2009) Blastocystis: unravelling potential risk factors and clinical significance of a common but neglected parasite. Epidemiol Infect 137: 1655-1663.
25. Mirza H, Tan KS (2012) Clinical Aspects of Blastocystis Infections: Advancements Amidst Controversies. In: Mehlhorn H, Tan KS, Yoshikawa H, editors. Blastocystis: Pathogen or Passenger? Verlag Berlin Heidelberg: Springer. pp. 65-84.
26. Boorom KF, Smith H, Nimri L, Viscogliosi E, Spanakos G, et al. (2008) Oh my aching gut: irritable bowel syndrome, Blastocystis, and asymptomatic infection. Parasit Vectors 1: 40.
27. Nagel R, Cuttell L, Stensvold CR, Mills PC, Bielefeldt-Ohmann H, et al. (2012) Blastocystis subtypes in symptomatic and asymptomatic family members and pets and response to therapy. Intern Med J 42: 1187-1195.
28. Dominguez-Marquez MV, Guna R, Munoz C, Gomez-Munoz MT, Borras R, (2009) High prevalence of subtype 4 among isolates of Blastocystis hominis from symptomatic patients of a health district of Valencia (Spain). Parasitol Res 105: 949-955.
29. Mirza H, Tan KS, (2009) Blastocystis exhibits inter- and intra-subtype variation in cysteine protease activity. Parasitol Res 104: 355-361.
30. Mirza H, Wu Z, Kidwai F, Tan KS, (2011) A metronidazole-resistant isolate of Blastocystis spp. is susceptible to nitric oxide and downregulates intestinal epithelial inducible nitric oxide synthase by a novel parasite survival mechanism. Infect Immun 79: 5019-5026.
31. Stensvold CR, Arendrup MC, Nielsen HV, Molbak K, (2009) [Blastocystis-an enigmatic parasite]. Ugeskr Laeger 171: 2388-2390.
32. Iguchi A, Ebisu A, Nagata S, Saitou Y, Yoshikawa H, et al. (2007) Infectivity of different genotypes of human Blastocystis hominis isolates in chickens and rats. Parasitol Int 56: 107-112.
33. Hussein EM, Hussein AM, Eida MM, Atwa MM, (2008) Pathophysiological variability of different genotypes of human Blastocystis hominis Egyptian isolates in experimentally infected rats. Parasitol Res 102: 853-860.
34. Denoeud F, Roussel M, Noel B, Wawrzyniak I, Da Silva C, et al. (2011) Genome sequence of the stramenopile Blastocystis, a human anaerobic parasite. Genome Biol 12: R29.
35. Wu B, Yin J, Texier C, Roussel M, Tan KS, (2010) Blastocystis legumain is localized on the cell surface, and specific inhibition of its activity implicates a pro-survival role for the enzyme. J Biol Chem 285: 1790-1798.
36. Mirza H, Wu Z, Teo JD, Tan KS, (2012) Statin pleiotropy prevents rho kinase-mediated intestinal epithelial barrier compromise induced by Blastocystis cysteine proteases. Cell Microbiol 14: 1474-1484.
37. Tan KS, Mirza H (2012) Blastocystis-Host Interactions: Insights from In Vitro Model Systems. In: Mehlhorn H, Tan KS, Yoshikawa H, editors. Blastocystis: Pathogen or Passenger? Verlag Berlin Heidelberg: Springer. pp. 51-63.
38. Elmendorf HG, Dawson SC, McCaffery JM, (2003) The cytoskeleton of Giardia lamblia. Int J Parasitol 33: 3-28.
39. Tavares P, Rigothier MC, Khun H, Roux P, Huerre M, et al. (2005) Roles of cell adhesion and cytoskeleton activity in Entamoeba histolytica pathogenesis: a delicate balance. Infect Immun 73: 1771-1778.
40. Brooks AE, Parsamand T, Kelly RW, Simoes-Barbosa A, (2013) An improved quantitative method to assess adhesive properties of Trichomonas vaginalis to host vaginal ectocervical cells using flow cytometry. J Microbiol Methods 92: 73-78.
41. Park BJ, Haines T, Abu-Lail NI, (2009) A correlation between the virulence and the adhesion of Listeria monocytogenes to silicon nitride: an atomic force microscopy study. Colloids Surf B Biointerfaces 73: 237-243.
42. Rojas L, Sariego I, Fraga J, Sarria CA, Sarracent J, et al. (2004) Use of in vitro cytoadherence assays in the comparative study of the virulence of isolates of Trichomonas vaginalis. Parasitol Res 93: 332-337.
43. Flores-Romo L, Estrada-Garcia T, Shibayama-Salas M, Campos-Rodriguez R, Bacon K, et al. (1997) In vitro Entamoeba histolytica adhesion to human endothelium: a comparison using two strains of different virulence. Parasitol Res 83: 397-400.
44. Muller N, von Allmen N, (2005) Recent insights into the mucosal reactions associated with Giardia lamblia infections. Int J Parasitol 35: 1339-1347.
45. van Hellemond JJ, Molhoek N, Koelewijn R, Wismans PJ, van Genderen PJ, (2013) Is paromomycin the drug of choice for eradication of Blastocystis in adults? J Infect Chemother 19: 545-548.
46. Moghaddam DD, Ghadirian E, Azami M, (2005) Blastocystis hominis and the evaluation of efficacy of metronidazole and trimethoprim/sulfamethoxazole. Parasitol Res 96: 273-275.
47. Stensvold CR, Arendrup MC, Nielsen HV, Bada A, Thorsen S, (2008) Symptomatic infection with Blastocystis sp. subtype 8 successfully treated with trimethoprim-sulfamethoxazole. Ann Trop Med Parasitol 102: 271-274.
48. Stensvold CR, Smith HV, Nagel R, Olsen KE, Traub RJ, (2009) Eradication of Blastocystis carriage with antimicrobials: reality or delusion? J Clin Gastroenterol 44: 85-90.
49. Mirza H, Teo JD, Upcroft J, Tan KS, (2011) A rapid, high-throughput viability assay for Blastocystis spp. reveals metronidazole resistance and extensive subtype-dependent variations in drug susceptibilities. Antimicrob Agents Chemother 55: 637-648.
50. Dunn LA, Tan KS, Vanelle P, Juspin T, Crozet MD, et al. (2012) Development of metronidazole-resistant lines of Blastocystis sp. Parasitol Res 111: 441-450.
51. Andersson DI, Hughes D, (2010) Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol 8: 260-271.
52. Ben-Ami R, Kontoyiannis DP, (2012) Resistance to echinocandins comes at a cost: the impact of FKS1 hotspot mutations on Candida albicans fitness and virulence. Virulence 3: 95-97.
53. Muregi FW, Ohta I, Masato U, Kino H, Ishih A, (2011) Resistance of a rodent malaria parasite to a thymidylate synthase inhibitor induces an apoptotic parasite death and imposes a huge cost of fitness. PLoS One 6: e21251.
54. Tejman-Yarden N, Millman M, Lauwaet T, Davids BJ, Gillin FD, et al. (2011) Impaired parasite attachment as fitness cost of metronidazole resistance in Giardia lamblia. Antimicrob Agents Chemother 55: 4643-4651.
55. Noel C, Dufernez F, Gerbod D, Edgcomb VP, Delgado-Viscogliosi P, et al. (2005) Molecular phylogenies of Blastocystis isolates from different hosts: implications for genetic diversity, identification of species, and zoonosis. J Clin Microbiol 43: 348-355.
56. Ho LC, Singh M, Suresh G, Ng GC, Yap EH, (1993) Axenic culture of Blastocystis hominis in Iscove's modified Dulbecco's medium. Parasitol Res 79: 614-616.
57. Stensvold CR, Suresh GK, Tan KS, Thompson RC, Traub RJ, et al. (2007) Terminology for Blastocystis subtypes-a consensus. Trends Parasitol 23: 93-96.
58. Chen XQ, Singh M, Ho LC, Moe KT, Tan SW, et al. (1997) A survey of Blastocystis sp. in rodents. Lab Anim Sci 47: 91-94.
59. Sio SW, Puthia MK, Lee AS, Lu J, Tan KS, (2006) Protease activity of Blastocystis hominis. Parasitol Res 99: 126-130.
60. Puthia MK, Vaithilingam A, Lu J, Tan KS, (2005) Degradation of human secretory immunoglobulin A by Blastocystis. Parasitol Res 97: 386-389.
61. Tan SW, Ho LC, Moe KT, Chen XQ, Ng GC, et al. (1996) Production and characterization of murine monoclonal antibodies to Blastocystis hominis. Int J Parasitol 26: 375-381.
62. Dagci H, Ustun S, Taner MS, Ersoz G, Karacasu F, et al. (2002) Protozoon infections and intestinal permeability. Acta Trop 81: 1-5.
63. Anderson JM, Van Itallie CM, (2009) Physiology and function of the tight junction. Cold Spring Harb Perspect Biol 1: a002584.
64. Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, et al. (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123: 1777-1788.
65. Andersson DI, (2006) The biological cost of mutational antibiotic resistance: any practical conclusions? Curr Opin Microbiol 9: 461-465.
66. Eckmann L, Laurent F, Langford TD, Hetsko ML, Smith JR, et al. (2000) Nitric oxide production by human intestinal epithelial cells and competition for arginine as potential determinants of host defense against the lumen-dwelling pathogen Giardia lamblia. J Immunol 164: 1478-1487.
67. Lewis ND, Asim M, Barry DP, Singh K, de Sablet T, et al. (2010) Arginase II restricts host defense to Helicobacter pylori by attenuating inducible nitric oxide synthase translation in macrophages. J Immunol 184: 2572-2582.
68. Eida OM, Hussein EM, Eida AM, El-Moamly AA, Salem AM, (2008) Evaluation of the nitric oxide activity against Blastocystis hominis in vitro and in vivo. J Egypt Soc Parasitol 38: 521-536.
69. Stensvold CR, Nielsen HV, Molbak K, Smith HV, (2009) Pursuing the clinical significance of Blastocystis-diagnostic limitations. Trends Parasitol 25: 23-29.
70. Garcia LS, (1984) Clinical relevance of Blastocystis hominis. Lancet 1: 1233-1234.
71. Waghorn DJ, Hancock P, (1991) Clinical significance of Blastocystis hominis. Lancet 337: 609.
72. Barry M, (2004) Travelers' Diarrhea. N Engl J Med 350: 1801-1803.
73. Turner JR, (2009) Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 9: 799-809.
74. Bonazzi M, Cossart P, (2011) Impenetrable barriers or entry portals? The role of cell-cell adhesion during infection. J Cell Biol 195: 349-358.
75. O'Hara JR, Buret AG, (2008) Mechanisms of intestinal tight junctional disruption during infection. Front Biosci 13: 7008-7021.
76. Sears CL, (2000) Molecular physiology and pathophysiology of tight junctions V. assault of the tight junction by enteric pathogens. Am J Physiol Gastrointest Liver Physiol 279: G1129-1134.
77. Berkes J, Viswanathan VK, Savkovic SD, Hecht G, (2003) Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation. Gut 52: 439-451.
78. Fasano A, Nataro JP, (2004) Intestinal epithelial tight junctions as targets for enteric bacteria-derived toxins. Adv Drug Deliv Rev 56: 795-807.
79. Peiffer I, Bernet-Camard MF, Rousset M, Servin AL, (2001) Impairments in enzyme activity and biosynthesis of brush border-associated hydrolases in human intestinal Caco-2/TC7 cells infected by members of the Afa/Dr family of diffusely adhering Escherichia coli. Cell Microbiol 3: 341-357.
80. McCarthy KM, Skare IB, Stankewich MC, Furuse M, Tsukita S, et al. (1996) Occludin is a functional component of the tight junction. J Cell Sci 109 (Pt 9): 2287-2298.
81. Maia-Brigagao C, Morgado-Diaz JA, De Souza W, (2012) Giardia disrupts the arrangement of tight, adherens and desmosomal junction proteins of intestinal cells. Parasitol Int 61: 280-287.
82. Ringqvist E, Avesson L, Soderbom F, Svard SG, (2011) Transcriptional changes in Giardia during host-parasite interactions. Int J Parasitol 41: 277-285.
83. Rodriguez-Fuentes GB, Cedillo-Rivera R, Fonseca-Linan R, Arguello-Garcia R, Munoz O, et al. (2006) Giardia duodenalis: analysis of secreted proteases upon trophozoite-epithelial cell interaction in vitro. Mem Inst Oswaldo Cruz 101: 693-696.
84. Wawrzyniak I, Texier C, Poirier P, Viscogliosi E, Tan KS, et al. (2012) Characterization of two cysteine proteases secreted by Blastocystis ST7, a human intestinal parasite. Parasitol Int 61: 437-442.
85. Reed SL, Keene WE, McKerrow JH, (1989) Thiol proteinase expression and pathogenicity of Entamoeba histolytica. J Clin Microbiol 27: 2772-2777.
86. Guimaraes S, Sogayar MI, Franco MF, (2003) Protease activity in Giardia duodenalis trophozoites of axenic strains isolated from symptomatic and asymptomatic patients. Mem Inst Oswaldo Cruz 98: 77-81.
87. Puthia MK, Lu J, Tan KS, (2008) Blastocystis ratti contains cysteine proteases that mediate interleukin-8 response from human intestinal epithelial cells in an NF-kappaB-dependent manner. Eukaryot Cell 7: 435-443.
88. Deneke CF, Thorne GM, Larson AD, Gorbach SL, (1985) Effect of tetracycline on the attachment of K88+ enterotoxigenic Escherichia coli to porcine small-intestinal cells. J Infect Dis 152: 1032-1036.
89. Klein U, Pawelzik M, Opferkuch W, (1985) Influence of beta-lactam antibiotics, fosfomycin and vancomycin on the adherence (hemagglutination) of Escherichia coli-containing different adhesins. Chemotherapy 31: 138-145.
90. Carlone NA, Borsotto M, Cuffini AM, Savoia D, (1987) Effect of fosfomycin trometamol on bacterial adhesion in comparison with other chemotherapeutic agents. Eur Urol 13 (Suppl 1): 86-91.
91. Li Pira G, Pruzzo C, Schito GC, (1987) Monuril and modification of pathogenicity traits in resistant microorganisms. Eur Urol 13 (Suppl 1): 92-97.
92. Gismondo MR, Drago L, Fassina C, Garlaschi ML, Rosina M, et al. (1994) Escherichia coli: effect of fosfomycin trometamol on some urovirulence factors. J Chemother 6: 167-172.
93. Nilsson AI, Berg OG, Aspevall O, Kahlmeter G, Andersson DI, (2003) Biological costs and mechanisms of fosfomycin resistance in Escherichia coli. Antimicrob Agents Chemother 47: 2850-2858.
94. Pompilio A, Catavitello C, Picciani C, Confalone P, Piccolomini R, et al. (2010) Subinhibitory concentrations of moxifloxacin decrease adhesion and biofilm formation of Stenotrophomonas maltophilia from cystic fibrosis. J Med Microbiol 59: 76-81.
95. Leitsch D, Burgess AG, Dunn LA, Krauer KG, Tan K, et al. (2011) Pyruvate:ferredoxin oxidoreductase and thioredoxin reductase are involved in 5-nitroimidazole activation while flavin metabolism is linked to 5-nitroimidazole resistance in Giardia lamblia. J Antimicrob Chemother 66: 1756-1765.
96. Leitsch D, Kolarich D, Duchene M, (2010) The flavin inhibitor diphenyleneiodonium renders Trichomonas vaginalis resistant to metronidazole, inhibits thioredoxin reductase and flavin reductase, and shuts off hydrogenosomal enzymatic pathways. Mol Biochem Parasitol 171: 17-24.
97. Upcroft P, Upcroft JA, (2001) Drug targets and mechanisms of resistance in the anaerobic protozoa. Clin Microbiol Rev 14: 150-164.
98. Ellis JE, Wingfield JM, Cole D, Boreham PF, Lloyd D, (1993) Oxygen affinities of metronidazole-resistant and-sensitive stocks of Giardia intestinalis. Int J Parasitol 23: 35-39.
99. Rasoloson D, Tomkova E, Cammack R, Kulda J, Tachezy J, (2001) Metronidazole-resistant strains of Trichomonas vaginalis display increased susceptibility to oxygen. Parasitology 123: 45-56.
100. Wawrzyniak I, Roussel M, Diogon M, Couloux A, Texier C, et al. (2008) Complete circular DNA in the mitochondria-like organelles of Blastocystis hominis. Int J Parasitol 38: 1377-1382.
101. Leitsch D, Kolarich D, Binder M, Stadlmann J, Altmann F, et al. (2009) Trichomonas vaginalis: metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system. Implications for nitroimidazole toxicity and resistance. Mol Microbiol 72: 518-536.
102. Mastronicola D, Testa F, Forte E, Bordi E, Pucillo LP, et al. (2010) Flavohemoglobin and nitric oxide detoxification in the human protozoan parasite Giardia intestinalis. Biochem Biophys Res Commun 399: 654-658.
103. Rafferty S, Luu B, March RE, Yee J, (2010) Giardia lamblia encodes a functional flavohemoglobin. Biochem Biophys Res Commun 399: 347-351.
104. Sebbane F, Lemaitre N, Sturdevant DE, Rebeil R, Virtaneva K, et al. (2006) Adaptive response of Yersinia pestis to extracellular effectors of innate immunity during bubonic plague. Proc Natl Acad Sci U S A 103: 11766-11771.
105. Roos V, Klemm P, (2006) Global gene expression profiling of the asymptomatic bacteriuria Escherichia coli strain 83972 in the human urinary tract. Infect Immun 74: 3565-3575.
106. Chen ML, Pothoulakis C, LaMont JT, (2002) Protein kinase C signaling regulates ZO-1 translocation and increased paracellular flux of T84 colonocytes exposed to Clostridium difficile toxin A. J Biol Chem. 277: 4247-4254.
107. Griffiths JK, Moore R, Dooley S, Keusch GT, Tzipori S, (1994) Cryptosporidium parvum infection of Caco-2 cell monolayers induces an apical monolayer defect, selectively increases transmonolayer permeability, and causes epithelial cell death. Infect Immun 62: 4506-4514.
108. Stenson WF, Zhang Z, Riehl T, Stanley SL Jr, (2001) Amebic infection in the human colon induces cyclooxygenase-2. Infect Immun 69: 3382-3388.
109. Chin AC, Teoh DA, Scott KG, Meddings JB, Macnaughton WK, et al. (2002) Strain-dependent induction of enterocyte apoptosis by Giardia lamblia disrupts epithelial barrier function in a caspase-3-dependent manner. Infect Immun 70: 3673-3680.
110. Buret AG, Mitchell K, Muench DG, Scott KG, (2002) Giardia lamblia disrupts tight junctional ZO-1 and increases permeability in non-transformed human small intestinal epithelial monolayers: effects of epidermal growth factor. Parasitology 125: 11-19.
111. Scott KG, Meddings JB, Kirk DR, Lees-Miller SP, Buret AG, (2002) Intestinal infection with Giardia spp. reduces epithelial barrier function in a myosin light chain kinase-dependent fashion. Gastroenterology 123: 1179-1190.