Publicação
The antimicrobial activity of sub3 is dependent on membrane binding and cell-penetrating ability
| dc.contributor.author | Torcato, Inês M. | |
| dc.contributor.author | Huang, Yen-Hua | |
| dc.contributor.author | Franquelim, Henri G. | |
| dc.contributor.author | Gaspar, Diana D. | |
| dc.contributor.author | Craik, David J. | |
| dc.contributor.author | Castanho, Miguel A. R. B. | |
| dc.contributor.author | Henriques, Sónia Troeira | |
| dc.date.accessioned | 2014-03-10T12:50:18Z | |
| dc.date.available | 2014-03-10T12:50:18Z | |
| dc.date.issued | 2013 | |
| dc.description | © 2013 Wiley-VCH Verlag GmbH& Co. KGaA, Weinheim | eng |
| dc.description.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. | eng |
| dc.description.sponsorship | I.M.T. work was funded by a grant from Fundação para a Ciência e a Tecnologia (FCT), Portugal (PTDC/SAU-BEB/099142/2008). H.G.F. and D.D.G. held a fellowship from FCT, Portugal, SFRH/BD/39039/2007 and SFRH/BPD/73500/2010, respectively. S.T.H. is the recipient of a Discovery Early Career Researcher Award (DE120103152), awarded by the Australian Research Council. D.J.C. is a National Health and Medical Research Council Fellow (APP1026501). Confocal microscopy imaging was performed at Australian Cancer Research foundation (ACRF)/Institute for Molecular Bioscience (IMB) dynamic imaging facility for cancer biology established with support of ACRF. We thank John Griffin (IMB, UQ) for the technical assistance with confocal microscopy imaging. | eng |
| dc.identifier.citation | ChemBioChem 2013, 14, 2013 – 2022 | por |
| dc.identifier.issn | 1439-4227 | |
| dc.identifier.uri | http://dx.doi.org/10.1002/cbic.201300274 | |
| dc.identifier.uri | http://hdl.handle.net/10451/10710 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Wiley | por |
| dc.relation.publisherversion | The definitive version is available at http://onlinelibrary.wiley.com/ | eng |
| dc.subject | Antibiotics | eng |
| dc.subject | Atomic force microscopy | eng |
| dc.subject | Internalization | eng |
| dc.subject | Membranes | eng |
| dc.subject | Peptides | eng |
| dc.title | The antimicrobial activity of sub3 is dependent on membrane binding and cell-penetrating ability | eng |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 2022 | por |
| oaire.citation.startPage | 2013 | por |
| oaire.citation.title | ChemBioChem | eng |
| oaire.citation.volume | 14 | por |
| rcaap.rights | closedAccess | por |
| rcaap.type | article | por |