Imaging the antimicrobial mechanism(s) of cathelicidin-2
Host defence peptides (HDPs) have the potential to become alternatives to conventional antibiotics in human and veterinary medicine. The HDP chicken cathelicidin-2 (CATH-2) has immunomodulatory and direct killing activities at micromolar concentrations. In this study the mechanism of action of CATH-...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Online |
| Language: | English |
| Published: |
Nature Publishing Group
2016
|
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021996/ |
| id |
pubmed-5021996 |
|---|---|
| recordtype |
oai_dc |
| spelling |
pubmed-50219962016-09-20 Imaging the antimicrobial mechanism(s) of cathelicidin-2 Schneider, Viktoria A. F. Coorens, Maarten Ordonez, Soledad R. Tjeerdsma-van Bokhoven, Johanna L. M. Posthuma, George van Dijk, Albert Haagsman, Henk P. Veldhuizen, Edwin J. A. Article Host defence peptides (HDPs) have the potential to become alternatives to conventional antibiotics in human and veterinary medicine. The HDP chicken cathelicidin-2 (CATH-2) has immunomodulatory and direct killing activities at micromolar concentrations. In this study the mechanism of action of CATH-2 against Escherichia coli (E. coli) was investigated in great detail using a unique combination of imaging and biophysical techniques. Live-imaging with confocal fluorescence microscopy demonstrated that FITC-labelled CATH-2 mainly localized at the membrane of E. coli. Upon binding, the bacterial membrane was readily permeabilized as was shown by propidium iodide influx into the cell. Concentration- and time-dependent effects of the peptide on E. coli cells were examined by transmission electron microscopy (TEM). CATH-2 treatment was found to induce dose-dependent morphological changes in E. coli. At sub-minimal inhibitory concentrations (sub-MIC), intracellular granulation, enhanced vesicle release and wrinkled membranes were observed, while membrane breakage and cell lysis occurred at MIC values. These effects were visible within 1–5 minute of peptide exposure. Immuno-gold TEM showed CATH-2 binding to bacterial membranes. At sub-MIC values the peptide rapidly localized intracellularly without visible membrane permeabilization. It is concluded that CATH-2 has detrimental effects on E. coli at concentrations that do not immediately kill the bacteria. Nature Publishing Group 2016-09-14 /pmc/articles/PMC5021996/ /pubmed/27624595 http://dx.doi.org/10.1038/srep32948 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Schneider, Viktoria A. F. Coorens, Maarten Ordonez, Soledad R. Tjeerdsma-van Bokhoven, Johanna L. M. Posthuma, George van Dijk, Albert Haagsman, Henk P. Veldhuizen, Edwin J. A. |
| spellingShingle |
Schneider, Viktoria A. F. Coorens, Maarten Ordonez, Soledad R. Tjeerdsma-van Bokhoven, Johanna L. M. Posthuma, George van Dijk, Albert Haagsman, Henk P. Veldhuizen, Edwin J. A. Imaging the antimicrobial mechanism(s) of cathelicidin-2 |
| author_facet |
Schneider, Viktoria A. F. Coorens, Maarten Ordonez, Soledad R. Tjeerdsma-van Bokhoven, Johanna L. M. Posthuma, George van Dijk, Albert Haagsman, Henk P. Veldhuizen, Edwin J. A. |
| author_sort |
Schneider, Viktoria A. F. |
| title |
Imaging the antimicrobial mechanism(s) of cathelicidin-2 |
| title_short |
Imaging the antimicrobial mechanism(s) of cathelicidin-2 |
| title_full |
Imaging the antimicrobial mechanism(s) of cathelicidin-2 |
| title_fullStr |
Imaging the antimicrobial mechanism(s) of cathelicidin-2 |
| title_full_unstemmed |
Imaging the antimicrobial mechanism(s) of cathelicidin-2 |
| title_sort |
imaging the antimicrobial mechanism(s) of cathelicidin-2 |
| description |
Host defence peptides (HDPs) have the potential to become alternatives to conventional antibiotics in human and veterinary medicine. The HDP chicken cathelicidin-2 (CATH-2) has immunomodulatory and direct killing activities at micromolar concentrations. In this study the mechanism of action of CATH-2 against Escherichia coli (E. coli) was investigated in great detail using a unique combination of imaging and biophysical techniques. Live-imaging with confocal fluorescence microscopy demonstrated that FITC-labelled CATH-2 mainly localized at the membrane of E. coli. Upon binding, the bacterial membrane was readily permeabilized as was shown by propidium iodide influx into the cell. Concentration- and time-dependent effects of the peptide on E. coli cells were examined by transmission electron microscopy (TEM). CATH-2 treatment was found to induce dose-dependent morphological changes in E. coli. At sub-minimal inhibitory concentrations (sub-MIC), intracellular granulation, enhanced vesicle release and wrinkled membranes were observed, while membrane breakage and cell lysis occurred at MIC values. These effects were visible within 1–5 minute of peptide exposure. Immuno-gold TEM showed CATH-2 binding to bacterial membranes. At sub-MIC values the peptide rapidly localized intracellularly without visible membrane permeabilization. It is concluded that CATH-2 has detrimental effects on E. coli at concentrations that do not immediately kill the bacteria. |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021996/ |
| _version_ |
1613650770416107520 |