Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 13 August 2004:
Vol. 305. no. 5686, pp. 1003 - 1006
DOI: 10.1126/science.1099250
Prev | Table of Contents | Next

Reports

Natural Antibiotic Function of a Human Gastric Mucin Against Helicobacter pylori Infection

Masatomo Kawakubo,1,2 Yuki Ito,1 Yukie Okimura,2 Motohiro Kobayashi,1,4 Kyoko Sakura,2 Susumu Kasama,1 Michiko N. Fukuda,4 Minoru Fukuda,4 Tsutomu Katsuyama,2 Jun Nakayama1,3*

Helicobacter pylori infects the stomachs of nearly a half the human population, yet most infected individuals remain asymptomatic, which suggests that there is a host defense against this bacterium. Because H. pylori is rarely found in deeper portions of the gastric mucosa, where O-glycans are expressed that have terminal {alpha}1,4-linked N-acetylglucosamine, we tested whether these O-glycans might affect H. pylori growth. Here, we report that these O-glycans have antimicrobial activity against H. pylori, inhibiting its biosynthesis of cholesteryl-{alpha}-D-glucopyranoside, a major cell wall component. Thus, the unique O-glycans in gastric mucin appeared to function as a natural antibiotic, protecting the host from H. pylori infection.

1 Department of Pathology, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
2 Department of Laboratory Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
3 Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
4 Glycobiology Program, Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

* To whom correspondence should be addressed. E-mail: jun{at}hsp.md.shinshu-u.ac.jp

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Glycosyltransferase Function in Core 2-Type Protein O Glycosylation.
E. L. Stone, M. N. Ismail, S. H. Lee, Y. Luu, K. Ramirez, S. M. Haslam, S. B. Ho, A. Dell, M. Fukuda, and J. D. Marth (2009)
Mol. Cell. Biol. 29, 3770-3782
   Abstract »    Full Text »    PDF »
Gastric Mucus Alterations Associated With Murine Helicobacter Infection.
J. M. Schmitz, C. G. Durham, S. B. Ho, and R. G. Lorenz (2009)
J. Histochem. Cytochem. 57, 457-467
   Abstract »    Full Text »    PDF »
Vertical Helicobacter pylori transmission from Mongolian gerbil mothers to pups.
I. Oshio, T. Osaki, T. Hanawa, H. Yonezawa, C. Zaman, S. Kurata, and S. Kamiya (2009)
J. Med. Microbiol. 58, 656-662
   Abstract »    Full Text »    PDF »
Roles of gastric mucin-type O-glycans in the pathogenesis of Helicobacter pylori infection.
M. Kobayashi, H. Lee, J. Nakayama, and M. Fukuda (2009)
Glycobiology 19, 453-461
   Abstract »    Full Text »    PDF »
Selection on cis-Regulatory Variation at B4galnt2 and Its Influence on von Willebrand Factor in House Mice.
J. M. Johnsen, M. Teschke, P. Pavlidis, B. M. McGee, D. Tautz, D. Ginsburg, and J. F. Baines (2009)
Mol. Biol. Evol. 26, 567-578
   Abstract »    Full Text »    PDF »
Campylobacter jejuni response to human mucin MUC2: modulation of colonization and pathogenicity determinants.
Q. V. Tu, M. A. McGuckin, and G. L. Mendz (2008)
J. Med. Microbiol. 57, 795-802
   Abstract »    Full Text »    PDF »
{alpha}1,4GlcNAc-capped mucin-type O-glycan inhibits cholesterol {alpha}-glucosyltransferase from Helicobacter pylori and suppresses H. pylori growth.
H. Lee, P. Wang, H. Hoshino, Y. Ito, M. Kobayashi, J. Nakayama, P. H Seeberger, and M. Fukuda (2008)
Glycobiology 18, 549-558
   Abstract »    Full Text »    PDF »
Identification and Expression of Human Epiglycanin/MUC21: a Novel Transmembrane Mucin.
Y. Itoh, M. Kamata-Sakurai, K. Denda-Nagai, S. Nagai, M. Tsuiji, K. Ishii-Schrade, K. Okada, A. Goto, M. Fukayama, and T. Irimura (2008)
Glycobiology 18, 74-83
   Abstract »    Full Text »    PDF »
A Distinctive Set of Genes Is Upregulated During the Inflammation-Carcinoma Sequence in Mouse Stomach Infected by Helicobacter felis.
M. Kobayashi, H. Lee, L. Schaffer, T. J. Gilmartin, S. R. Head, S. Takaishi, T. C. Wang, J. Nakayama, and M. Fukuda (2007)
J. Histochem. Cytochem. 55, 263-274
   Abstract »    Full Text »    PDF »
Development of Immunoglobulin A Nephropathy- Like Disease in {beta}-1,4-Galactosyltransferase-I-Deficient Mice.
T. Nishie, O. Miyaishi, H. Azuma, A. Kameyama, C. Naruse, N. Hashimoto, H. Yokoyama, H. Narimatsu, T. Wada, and M. Asano (2007)
Am. J. Pathol. 170, 447-456
   Abstract »    Full Text »    PDF »
Construction of a Library of Human Glycosyltransferases Immobilized in the Cell Wall of Saccharomyces cerevisiae.
Y.-i. Shimma, F. Saito, F. Oosawa, and Y. Jigami (2006)
Appl. Envir. Microbiol. 72, 7003-7012
   Abstract »    Full Text »    PDF »
Helicobacter pylori Persistence: an Overview of Interactions between H. pylori and Host Immune Defenses.
H. M. S. Algood and T. L. Cover (2006)
Clin. Microbiol. Rev. 19, 597-613
   Abstract »    Full Text »    PDF »
Cloning of a Cholesterol-{alpha}-glucosyltransferase from Helicobacter pylori.
A.-H. Lebrun, C. Wunder, J. Hildebrand, Y. Churin, U. Zahringer, B. Lindner, T. F. Meyer, E. Heinz, and D. Warnecke (2006)
J. Biol. Chem. 281, 27765-27772
   Abstract »    Full Text »    PDF »
Terminal {alpha}1,4-linked N-acetylglucosamine in Helicobacter pylori-associated Intestinal Metaplasia of the Human Stomach and Gastric Carcinoma Cell Lines..
B. Ferreira, N. T. Marcos, L. David, J. Nakayama, and C. A. Reis (2006)
J. Histochem. Cytochem. 54, 585-591
   Abstract »    Full Text »    PDF »
Dynamic Association between the Catalytic and Lectin Domains of Human UDP-GalNAc:Polypeptide {alpha}-N-Acetylgalactosaminyltransferase-2.
T. A. Fritz, J. Raman, and L. A. Tabak (2006)
J. Biol. Chem. 281, 8613-8619
   Abstract »    Full Text »    PDF »
The antioxidant protein alkylhydroperoxide reductase of Helicobacter pylori switches from a peroxide reductase to a molecular chaperone function.
M.-H. Chuang, M.-S. Wu, W.-L. Lo, J.-T. Lin, C.-H. Wong, and S.-H. Chiou (2006)
PNAS 103, 2552-2557
   Abstract »    Full Text »    PDF »
Helicobacter pylori and cholesterol gallstone formation in C57L/J mice: a prospective study.
K. J. Maurer, A. B. Rogers, Z. Ge, A. J. Wiese, M. C. Carey, and J. G. Fox (2006)
Am J Physiol Gastrointest Liver Physiol 290, G175-G182
   Abstract »    Full Text »    PDF »
A Novel Bacterial Mucinase, Glycosulfatase, Is Associated with Bacterial Vaginosis.
A. M. Roberton, R. Wiggins, P. J. Horner, R. Greenwood, T. Crowley, A. Fernandes, M. Berry, and A. P. Corfield (2005)
J. Clin. Microbiol. 43, 5504-5508
   Abstract »    Full Text »    PDF »
Differential Steroidogenic Gene Expression in the Fetal Adrenal Gland Versus the Testis and Rapid and Dynamic Response of the Fetal Testis to Di(n-butyl) Phthalate.
C. J. Thompson, S. M. Ross, J. Hensley, K. Liu, S. C. Heinze, S. S. Young, and K. W. Gaido (2005)
Biol Reprod 73, 908-917
   Abstract »    Full Text »    PDF »
Events at the Host-Microbial Interface of the Gastrointestinal Tract IV. The pathogenesis of Helicobacter pylori persistence.
R. M. Peek Jr. (2005)
Am J Physiol Gastrointest Liver Physiol 289, G8-G12
   Abstract »    Full Text »    PDF »
Induction of peripheral lymph node addressin in human gastric mucosa infected by Helicobacter pylori.
M. Kobayashi, J. Mitoma, N. Nakamura, T. Katsuyama, J. Nakayama, and M. Fukuda (2004)
PNAS 101, 17807-17812
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)