AEM
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Other Versions of this Article:
AEM.01388-06v1
72/12/7694    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 Termont, S.
Right arrow Articles by Rottiers, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Termont, S.
Right arrow Articles by Rottiers, P.
Agricola
Right arrow Articles by Termont, S.
Right arrow Articles by Rottiers, P.

 Previous Article  |  Next Article 

Applied and Environmental Microbiology, December 2006, p. 7694-7700, Vol. 72, No. 12
0099-2240/06/$08.00+0     doi:10.1128/AEM.01388-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Intracellular Accumulation of Trehalose Protects Lactococcus lactis from Freeze-Drying Damage and Bile Toxicity and Increases Gastric Acid Resistance{triangledown}

Sofie Termont,1 Klaas Vandenbroucke,1 Dirk Iserentant,2 Sabine Neirynck,1,{dagger} Lothar Steidler,1,{dagger} Erik Remaut,1 and Pieter Rottiers1*

Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University, Technologiepark 927, B-9052 Ghent, Belgium,1 Flanders Interuniversity Institute for Biotechnology, Rijvisschestraat 120, B-9052 Ghent, Belgium2

Received 15 June 2006/ Accepted 25 September 2006

Interleukin-10 (IL-10) is a promising candidate for the treatment of inflammatory bowel disease. Intragastric administration of Lactococcus lactis genetically modified to secrete IL-10 in situ in the intestine was shown to be effective in healing and preventing chronic colitis in mice. However, its use in humans is hindered by the sensitivity of L. lactis to freeze-drying and its poor survival in the gastrointestinal tract. We expressed the trehalose synthesizing genes from Escherichia coli under control of the nisin-inducible promoter in L. lactis. Induced cells accumulated intracellular trehalose and retained nearly 100% viability after freeze-drying, together with a markedly prolonged shelf life. Remarkably, cells producing trehalose were resistant to bile, and their viability in human gastric juice was enhanced. None of these effects were seen with exogenously added trehalose. Trehalose accumulation did not interfere with IL-10 secretion or with therapeutic efficacy in murine colitis. The newly acquired properties should enable a larger proportion of the administered bacteria to reach the gastrointestinal tract in a bioactive form, providing a means for more effective mucosal delivery of therapeutics.

* Corresponding author. Mailing address: Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB) and Ghent University, Technologiepark 927, B-9052 Ghent, Belgium. Phone: 32 9 3313660. Fax: 32 9 3313609. E-mail: Pieter.Rottiers{at}ActoGeniX.com.

{triangledown} Published ahead of print on 6 October 2006.

{dagger} Present address: Alimentary Pharmabiotic Centre, Transgenic Bacteriology, University College Cork, Western Road, Cork, Ireland.

Applied and Environmental Microbiology, December 2006, p. 7694-7700, Vol. 72, No. 12
0099-2240/06/$08.00+0     doi:10.1128/AEM.01388-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. Microbiol. Mol. Biol. Rev. Eukaryot. Cell All ASM Journals

Copyright © 2006 by the American Society for Microbiology. All rights reserved.