HumanClostridium difficileinfection: altered mucus production and composition

American Journal of Physiology - Gastrointestinal and Liver Physiology - Tập 308 Số 6 - Trang G510-G524 - 2015
Melinda A. Engevik1, Mary Beth Yacyshyn2, Kristen A. Engevik1, Jiang Wang3, Benjamin J. Darien4, Daniel J. Hassett5, Bruce Yacyshyn2,6, Roger T. Worrell1,6
1Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio
2Department of Medicine Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio;
3Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
4Department of Animal Health and Biomedical Sciences, University Wisconsin, Madison, Wisconsin; and
5Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio
6Digestive Health Center of Cincinnati Children's Hospital, Cincinnati, Ohio

Tóm tắt

The majority of antibiotic-induced diarrhea is caused by Clostridium difficile ( C. difficile). Hospitalizations for C. difficile infection (CDI) have tripled in the last decade, emphasizing the need to better understand how the organism colonizes the intestine and maintain infection. The mucus provides an interface for bacterial-host interactions and changes in intestinal mucus have been linked host health. To assess mucus production and composition in healthy and CDI patients, the main mucins MUC1 and MUC2 and mucus oligosaccharides were examined. Compared with healthy subjects, CDI patients demonstrated decreased MUC2 with no changes in surface MUC1. Although MUC1 did not change at the level of the epithelia, MUC1 was the primary constituent of secreted mucus in CDI patients. CDI mucus also exhibited decreased N-acetylgalactosamine (GalNAc), increased N-acetylglucosamine (GlcNAc), and increased terminal galactose residues. Increased galactose in CDI specimens is of particular interest since terminal galactose sugars are known as C. difficile toxin A receptor in animals. In vitro, C. difficile is capable of metabolizing fucose, mannose, galactose, GlcNAc, and GalNAc for growth under healthy stool conditions (low Na+concentration, pH 6.0). Injection of C. difficile into human intestinal organoids (HIOs) demonstrated that C. difficile alone is sufficient to reduce MUC2 production but is not capable of altering host mucus oligosaccharide composition. We also demonstrate that C. difficile binds preferentially to mucus extracted from CDI patients compared with healthy subjects. Our results provide insight into a mechanism of C. difficile colonization and may provide novel target(s) for the development of alternative therapeutic agents.

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Tài liệu tham khảo

10.1128/IAI.01520-08

10.1128/IAI.71.10.5565-5575.2003

10.1177/0148607112446703

10.1128/IAI.01432-07

10.1016/S0924-8579(09)70018-4

10.1016/0966-842X(96)10057-3

10.1128/IAI.00093-07

10.1371/journal.ppat.1000902

10.1099/00222615-21-4-299

10.1111/j.1365-2672.1979.tb02581.x

10.1099/00222615-24-1-53

Borriello SP, J Antimicrob Chemother, 7

10.1053/gast.1997.v112.pm9178681

10.1016/j.tim.2012.04.001

10.1126/science.273.5280.1380

10.1128/IAI.70.10.5770-5778.2002

Caldwell DR, 1974, J Bacteriol, 120, 322, 10.1128/JB.120.1.322-333.1974

Caldwell DR, 1973, J Bacteriol, 114, 782, 10.1128/JB.114.2.782-789.1973

10.1053/gast.1996.v111.pm8690209

10.1016/j.vetmic.2005.11.055

10.1371/journal.pone.0039743

10.1016/0003-9861(87)90561-3

Cohen M, 2012, J Vis Exp, 67, e3928

Corfield AP, 1992, Infect Immun, 60, 3971, 10.1128/IAI.60.10.3971-3978.1992

10.1128/IAI.68.6.3172-3179.2000

10.1093/ajcn/73.6.1131S

10.1016/S0925-4439(98)00010-6

10.1172/JCI115957

10.1152/ajpgi.00184.2013

10.1152/ajpgi.00090.2014

10.1159/000356632

10.1007/s004240050325

10.1111/j.1365-2958.1993.tb01129.x

10.1073/pnas.0906425106

10.1128/AEM.71.7.4117-4120.2005

Finlay BB, 1989, Microbiol Rev, 53, 210, 10.1128/MMBR.53.2.210-230.1989

10.1136/gut.2003.031245

Freitas M, 2002, Histochem Cell Biol, 118, 149, 10.1007/s00418-002-0432-0

10.1172/JCI45538

Galili U, 1988, Infect Immun, 56, 1730, 10.1128/IAI.56.7.1730-1737.1988

10.1016/j.biocel.2007.12.014

10.1038/nsmb1084

10.1111/j.1472-765X.2008.02408.x

10.1172/JCI115706

10.1007/BF00393667

10.1099/mic.0.26145-0

10.1038/mi.2009.132

10.1073/pnas.0506391102

10.1146/annurev.nutr.22.011602.092259

10.1073/pnas.96.17.9833

10.1099/0022-1317-51-5-448

10.1172/JCI110009

10.1128/IAI.00515-13

10.1007/s00018-011-0822-3

10.1073/pnas.1006451107

10.1073/pnas.0803124105

10.1016/j.tim.2011.10.001

Juntunen M, 2001, Clin Diagn Lab Immunol, 8, 293, 10.1128/CDLI.8.2.293-296.2001

10.1111/j.1348-0421.2007.tb03916.x

10.1007/s11894-010-0131-2

Krivan HC, 1986, Infect Immun, 53, 573, 10.1128/IAI.53.3.573-581.1986

10.4491/eer.2009.14.1.019

Leitch GJ, 1988, Infect Immun, 56, 2871, 10.1128/IAI.56.11.2871-2875.1988

10.1152/ajpgi.1990.258.1.G96

10.1152/ajplung.2001.280.1.L181

10.1038/mi.2008.5

10.1128/IAI.69.2.1120-1126.2001

10.1136/gut.52.6.827

10.1093/glycob/cwp131

Mantle M, 1989, Infect Immun, 57, 3292, 10.1128/IAI.57.11.3292-3299.1989

10.1007/s00383-002-0855-7

10.1038/nrmicro2538

10.1038/srep03145

10.1053/j.gastro.2010.04.005

10.1038/nature12503

10.1128/IAI.72.10.6040-6049.2004

10.1016/S1286-4579(02)01636-2

10.1152/ajpgi.00243.2009

10.1128/JCM.42.6.2566-2572.2004

10.1111/j.1574-6968.1999.tb13450.x

10.1136/gutjnl-2012-303184

10.1097/00042737-199611000-00003

10.1053/gast.1996.v110.pm8964394

10.1172/JCI118835

Probert HM, 2002, Curr Issues Intest Microbiol, 3, 23

10.1136/gut.35.3.353

10.1161/01.HYP.0000184362.61744.c1

10.1023/A:1006844125976

10.1099/00207713-50-1-251

10.1128/AEM.02509-07

10.1093/ajcn/32.1.158

Salyers AA, 1977, Appl Environ Microbiol, 33, 319, 10.1128/AEM.33.2.319-322.1977

10.1099/00221287-148-11-3651

10.1038/ni.1825

10.1111/j.1574-6968.2010.02185.x

10.1128/IAI.00319-08

10.1111/j.1440-1746.2011.06909.x

10.1136/pmj.76.898.473

10.1099/00222615-46-11-953

10.1007/978-1-61779-024-9_6

10.1016/S0140-6736(89)92749-9

10.1371/journal.pone.0079883

10.1023/A:1007015312036

Waligora AJ, 1999, Appl Environ Microbiol, 65, 4234, 10.1128/AEM.65.9.4234-4238.1999

10.1128/IAI.69.4.2144-2153.2001

10.1186/scrt362

Wilson KH, 1988, Infect Immun, 56, 2610, 10.1128/IAI.56.10.2610-2614.1988

10.1128/IAI.00854-13

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American Journal of Physiology - Gastrointestinal and Liver Physiology

Tập 308 Số 6

G510-G524

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