Cell entry and antimicrobial properties of eukaryotic cell‐ penetrating peptides
| Autor: | Liam Good, Gunaratna Kuttuva Rajarao, Mattias Hällbrink, Natalia Nekhotiaeva, Anna Elmquist, Ülo Langel |
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| Rok vydání: | 2003 |
| Předmět: |
Cell Membrane Permeability
Cells Antimicrobial peptides Biology Biochemistry Microbiology HeLa Anti-Infective Agents Species Specificity Genetics Humans Cytotoxicity Molecular Biology Bacteria Intracellular parasite Mycobacterium smegmatis Cell Membrane Fungi biology.organism_classification Antimicrobial Cell culture Drug delivery Peptides Cell Division HeLa Cells Biotechnology |
| Zdroj: | The FASEB Journal. 18:1-15 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | Antimicrobial drug action is limited by both microbial and host cell membranes. Microbes stringently exclude the entry of most drugs, and mammalian membranes limit drug distribution and access to intracellular pathogens. Recently, cell-penetrating peptides (CPPs) have been developed as carriers to improve mammalian cell uptake. Given that CPPs are cationic and often amphipathic, similar to membrane active antimicrobial peptides, it may be possible to use CPP activity to improve drug delivery to microbes. Here, two CPPs, TP10 and pVEC, were found to enter a range of bacteria and fungi. The uptake route involves rapid surface accumulation within minutes followed by cell entry. TP10 inhibited Candida albicans and Staphylococcus aureus growth, and pVEC inhibited Mycobacterium smegmatis growth at low micromolar doses, below the levels that harmed human HeLa cells. Therefore, although TP10 and pVEC entered all cell types tested, they preferentially damage microbes, and this effect was sufficient to clear HeLa cell cultures from noninvasive S. aureus infection. Also, conversion of the cytotoxicity indicator dye SYTOX Green showed that TP10 causes rapid and lethal permeabilization of S. aureus and pVEC permeabilizes M. smegmatis, but not HeLa cells. Therefore, TP10 and pVEC can enter both mammalian and microbial cells and preferentially permeabilize and kill microbes. |
| Databáze: | OpenAIRE |
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