Cell-penetrating antimicrobial peptides - prospectives for targeting intracellular infections

Pharmaceutical Research
Jesper Søborg BahnsenHanne Mørck Nielsen

Abstract

To investigate the suitability of three antimicrobial peptides (AMPs) as cell-penetrating antimicrobial peptides. Cellular uptake of three AMPs (PK-12-KKP, SA-3 and TPk) and a cell-penetrating peptide (penetratin), all 5(6)-carboxytetramethylrhodamine-labeled, were tested in HeLa WT cells and analyzed by flow cytometry and confocal microscopy. Furthermore, the effects of the peptides on eukaryotic cell viability as well as their antimicrobial effect were tested. In addition, the disrupting ability of the peptides in the presence of bilayer membranes of different composition were analyzed. AMP uptake relative to penetratin was ~13% (PK-12-KKP), ~66% (SA-3) and ~50% (TPk). All four peptides displayed a punctate uptake pattern in HeLa WT cells with co-localization to lysosomes and no indication that clathrin-mediated endocytosis was the predominant uptake mechanism. TPk showed the highest antibacterial activity. SA-3 exhibited selective disruption of liposomes mimicking Gram-positive and Gram-negative membranes. PK-12-KKP is an unlikely candidate for targeting intracellular bacteria, as the eukaryotic cell-penetrating ability is poor. SA-3, affected the cellular viability to an unacceptable degree. TPk showed acceptable uptake eff...Continue Reading

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Citations

Oct 26, 2016·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Cristina Prat, Alicia Lacoma
May 27, 2017·Chemical Biology & Drug Design·Urszula PiotrowskaEwa Oledzka
Jul 11, 2018·Frontiers in Chemistry·Patrícia M CarvalhoMarco M Domingues
May 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Malgorzata Miazga-KarskaGrazyna Ginalska
Nov 2, 2019·Biochimica Et Biophysica Acta. Biomembranes·Mobashar Hussain Urf Turabe FazilRathi Saravanan
Apr 21, 2021·Expert Opinion on Drug Discovery·Ly PoroskÜlo Langel
Jul 28, 2021·Chemical Biology & Drug Design·Samantha M Zeiders, Jean Chmielewski
Oct 8, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Marcio M AlmeidaKarin A Riske

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