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Cell entry and antimicrobial properties of eukaryotic cell‐ penetrating peptides
Author(s) -
Nekhotiaeva Natalia,
Elmquist Anna,
Rajarao Gunaratna Kuttuva,
Hällbrink Mattias,
Langel Ülo,
Good Liam
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0449fje
Subject(s) - mycobacterium smegmatis , hela , intracellular , candida albicans , cell , antimicrobial , cell penetrating peptide , cytotoxicity , cell membrane , microbiology and biotechnology , staphylococcus aureus , chemistry , antimicrobial peptides , bacteria , biology , biochemistry , in vitro , mycobacterium tuberculosis , medicine , tuberculosis , genetics , pathology
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 p VEC, 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 p VEC inhibited Mycobacterium smegmatis growth at low micromolar doses, below the levels that harmed human HeLa cells. Therefore, although TP10 and p VEC 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 p VEC permeabilizes M. smegmatis , but not HeLa cells. Therefore, TP10 and p VEC can enter both mammalian and microbial cells and preferentially permeabilize and kill microbes.