The Antimicrobial Activity of Sub3 is Dependent on Membrane Binding and Cell-Penetrating Ability

Torcato, Ines M., Huang, Yen-Hua, Franquelim, Henri G., Gaspar, Diana D., Craik, David J., Castanho, Miguel A. R. B. and Henriques, Sonia Troeira (2013) The Antimicrobial Activity of Sub3 is Dependent on Membrane Binding and Cell-Penetrating Ability. Chembiochem, 14 15: 2013-2022. doi:10.1002/cbic.201300274

Author Torcato, Ines M.
Huang, Yen-Hua
Franquelim, Henri G.
Gaspar, Diana D.
Craik, David J.
Castanho, Miguel A. R. B.
Henriques, Sonia Troeira
Title The Antimicrobial Activity of Sub3 is Dependent on Membrane Binding and Cell-Penetrating Ability
Journal name Chembiochem   Check publisher's open access policy
ISSN 1439-4227
Publication date 2013-10-01
Year available 2013
Sub-type Article (original research)
DOI 10.1002/cbic.201300274
Volume 14
Issue 15
Start page 2013
End page 2022
Total pages 10
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag GmbH & Co. KGaA
Language eng
Formatted abstract
Because of their high activity against microorganisms and low cytotoxicity, cationic antimicrobial peptides (AMPs) have been explored as the next generation of antibiotics. Although they have common structural features, the modes of action of AMPs are extensively debated, and a single mechanism does not explain the activity of all AMPs reported so far. Here we investigated the mechanism of action of Sub3, an AMP previously designed and optimised from high-throughput screening with bactenecin as the template. Sub3 has potent activity against Gram-negative and Gram-positive bacteria as well as against fungi, but its mechanism of action has remained elusive. By using AFM imaging, ζ potential, flow cytometry and fluorescence methodologies with model membranes and bacterial cells, we found that, although the mechanism of action involves membrane targeting, Sub3 internalises inside bacteria at lethal concentrations without permeabilising the membrane, thus suggesting that its antimicrobial activity might involve both the membrane and intracellular targets. In addition, we found that Sub3 can be internalised into human cells without being toxic. As some bacteria are able to survive intracellularly and consequently evade host defences and antibiotic treatment, our findings suggest that Sub3 could be useful as an intracellular antimicrobial agent for infections that are notoriously difficult to treat.
Keyword Antibiotics
Atomic force microscopy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 20 times in Thomson Reuters Web of Science Article | Citations
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