Eukaryotic Cell
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Other Versions of this Article:
EC.00120-07v1
6/8/1486    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jong, A.
Right arrow Articles by Huang, S.-H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jong, A.
Right arrow Articles by Huang, S.-H.

 Previous Article  |  Next Article 

Eukaryotic Cell, August 2007, p. 1486-1496, Vol. 6, No. 8
1535-9778/07/$08.00+0     doi:10.1128/EC.00120-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Identification and Characterization of CPS1 as a Hyaluronic Acid Synthase Contributing to the Pathogenesis of Cryptococcus neoformans Infection{triangledown}

Ambrose Jong,1* Chun-Hua Wu,1 Han-Min Chen,2 Feng Luo,1 Kyung J. Kwon-Chung,3 Yun C. Chang,3 Craig W. LaMunyon,4 Anna Plaas,5 and Sheng-He Huang6

Divisions of Hematology-Oncology,1 Infectious Diseases, Children's Hospital Los Angeles, Los Angeles, California 90027,6 Department of Life Science, Fu-Jen University, Taiwan, Republic of China,2 Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,3 Department of Biological Sciences, California State Polytechnic University, Pomona, California 91768,4 Section of Rheumatology, Rush University, Chicago, Illinois 606125

Received 11 April 2007/ Accepted 21 May 2007

Cryptococcus neoformans is a pathogenic yeast that often causes devastating meningoencephalitis in immunocompromised individuals. We have previously identified the C. neoformans CPS1 gene, which is required for a capsular layer on the outer cell wall. In this report, we investigate the function of the CPS1 gene and its pathogenesis. We demonstrated that treatment of yeast with either 4-methylumbelliferone or hyaluronidase resulted in a reduction of the level of C. neoformans binding to human brain microvascular endothelial cells (HBMEC). Yeast extracellular structures were also altered accordingly in hyaluronidase-treated cells. Furthermore, observation of yeast strains with different hyaluronic acid contents showed that the ability to bind to HBMEC is proportional to the hyaluronic acid content. A killing assay with Caenorhabditis elegans demonstrated that the CPS1 wild-type strain is more virulent than the cps1{Delta} strain. When CPS1 is expressed in Saccharomyces cerevisiae and Escherichia coli, hyaluronic acid can be detected in the cells. Additionally, we determined by fluorophore-assisted carbohydrate electrophoretic analysis that hyaluronic acid is a component of the C. neoformans capsule. The size of hyaluronic acid molecules is evaluated by gel filtration and transmission electron microscopy studies. Together, our results support that C. neoformans CPS1 encodes hyaluronic acid synthase and that its product, hyaluronic acid, plays a role as an adhesion molecule during the association of endothelial cells with yeast.

* Corresponding author. Mailing address: Division of Hematology-Oncology, Children's Hospital Los Angeles, Los Angeles, CA 90027. Phone: (323) 669-5647. Fax: (323) 953 9940. E-mail: ajong{at}chla.usc.edu

{triangledown} Published ahead of print on 1 June 2007.

Eukaryotic Cell, August 2007, p. 1486-1496, Vol. 6, No. 8
1535-9778/07/$08.00+0     doi:10.1128/EC.00120-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Appl. Environ. Microbiol. Infect. Immun. J. Bacteriol.
Mol. Cell Biol. Microbiol. Mol. Biol. Rev. ALL ASM JOURNALS
Copyright © 2007 by the American Society for Microbiology.