Skip Navigation


JAC Advance Access originally published online on February 12, 2009
Journal of Antimicrobial Chemotherapy 2009 63(4):679-686; doi:10.1093/jac/dkn552
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
63/4/679    most recent
dkn552v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Swe, P. M.
Right arrow Articles by Jack, R. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Swe, P. M.
Right arrow Articles by Jack, R. W.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Mode of action of dysgalacticin: a large heat-labile bacteriocin

Pearl M. Swe, Gregory M. Cook, John R. Tagg and Ralph W. Jack*

Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, PO Box 56, Dunedin, New Zealand

Received 15 September 2008; returned 11 November 2008; revised 21 December 2008; accepted 22 December 2008

* Corresponding author. Seperex Nutritionals Ltd, Suite 23, The Centre for Innovation, PO Box 56, Dunedin, New Zealand. Tel: +64-3-479-9974; Fax: +64-3-479-4089; E-mail: ralph.jack{at}seperex.co.nz

Objectives: The mode of action of dysgalacticin, a large (21.5 kDa), heat-labile bacteriocin that is active against the human pathogen Streptococcus pyogenes, was investigated.

Methods: We used recombinant dysgalacticin to determine its mode of action against S. pyogenes. Antimicrobial activity of dysgalacticin was determined by MIC assays and viability counts. The extracellular pH of glucose-energized S. pyogenes cell suspensions was measured to determine the influence of dysgalacticin on glucose fermentation. To examine the effect of dysgalacticin on glucose transport, uptake of [14C]glucose and the non-metabolizable analogue [3H]2-deoxyglucose (2DG) was measured. Furthermore, the effect of dysgalacticin on membrane integrity, intracellular potassium concentration, membrane potential and [14C]serine uptake was determined.

Results: Dysgalacticin was bactericidal towards S. pyogenes and inhibited glucose fermentation by non-growing cell suspensions. Dysgalacticin blocked transport of both glucose and 2DG, indicating that dysgalacticin targets the phosphoenolpyruvate-dependent glucose- and mannose-phosphotransferase system (PTS) of S. pyogenes. This inhibitory activity was voltage-independent, and in addition to the inhibition of glucose transport, dysgalacticin increased the permeability of the cytoplasmic membrane mediating leakage of intracellular potassium ions. Moreover, dysgalacticin dissipated the membrane potential and inhibited [14C]serine uptake, a membrane potential-dependent process in S. pyogenes.

Conclusions: Taken together, these data indicate that dysgalacticin targets the glucose- and/or mannose-PTS as a receptor leading to inhibition of sugar uptake. As a result of this interaction, dysgalacticin perturbs membrane integrity leading to loss of intracellular K+ ions and dissipation of the membrane potential, ultimately leading to cell death.

Keywords: bacteriocins , membrane potential , glucose-PTS , mannose-PTS


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.