The bactericidal activity of temporin analogues against methicillin resistant Staphylococcus aureus

Anna Golda , Paulina Kosikowska-Adamus , Aleksandra Kret , Olena Babyak , Kinga Wójcik , Ewelina Dobosz , Jan Potempa , Adam Lesner , Joanna Kozieł

Abstract

Staphylococcus aureus is a major infectious agent responsible for a plethora of superficial skin infections and systemic diseases, including endocarditis and septic arthritis. Recent epidemiological data revealed the emergence of resistance to commonly used antibiotics, including increased numbers of both hospital- and community-acquired methicillin-resistant S. aureus (MRSA). Due to their potent antimicrobial functions, low potential to develop resistance, and immunogenicity, antimicrobial peptides (AMPs) are a promising alternative treatment for multidrug-resistant strains. Here, we examined the activity of a lysine-rich derivative of amphibian temporin-1CEb (DK5) conjugated to peptides that exert pro-proliferative and/or cytoprotective activity. Analysis of a library of synthetic peptides to identify those with antibacterial potential revealed that the most potent agent against multidrug-resistant S. aureus was a conjugate of a temporin analogue with the synthetic Leu-enkephalin analogue dalargin (DAL). DAL-PEG-DK5 exerted direct bactericidal effects via bacterial membrane disruption, leading to eradication of both planktonic and biofilm-associated staphylococci. Finally, we showed that accumulation of the peptide in the cytoplasm of human keratinocytes led to a marked clearance of intracellular MRSA, resulting in cytoprotection against invading bacteria. Collectively, the data showed that DAL-PEG-DK5 might be a potent antimicrobial agent for treatment of staphylococcal skin infections.
Author Anna Golda - [Uniwersytet Jagielloński w Krakowie]
Anna Golda,,
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, Paulina Kosikowska-Adamus (FCh / DOCh / LChB)
Paulina Kosikowska-Adamus,,
- Laboratory of Chemistry of Biopolymers
, Aleksandra Kret - [Uniwersytet Jagielloński w Krakowie]
Aleksandra Kret,,
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, Olena Babyak - [Uniwersytet Jagielloński w Krakowie]
Olena Babyak,,
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, Kinga Wójcik - [Uniwersytet Jagielloński w Krakowie]
Kinga Wójcik,,
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, Ewelina Dobosz - [Uniwersytet Jagielloński w Krakowie]
Ewelina Dobosz,,
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, Jan Potempa - [Uniwersytet Jagielloński w Krakowie]
Jan Potempa,,
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, Adam Lesner (FCh / DET / LBAN)
Adam Lesner,,
- Laboratory of Biochemical Analytics and Nanodiagnostics
, Joanna Kozieł - [Uniwersytet Jagielloński w Krakowie]
Joanna Kozieł,,
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Journal seriesInternational Journal of Molecular Sciences, ISSN 1422-0067, (N/A 140 pkt)
Issue year2019
Vol20
No19
Pages1-16
Article number4761
Keywords in Englishtemporin, MRSA, antimicrobial peptide, human keratinocytes
ASJC Classification2700 General Medicine; 1312 Molecular Biology; 1503 Catalysis; 1604 Inorganic Chemistry; 1605 Organic Chemistry; 1606 Physical and Theoretical Chemistry; 1607 Spectroscopy; 1706 Computer Science Applications
DOIDOI:10.3390/ijms20194761
URL https://doi.org/10.3390/ijms20194761
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)140
Score sourcejournalList
ScoreMinisterial score = 140.0, 20-03-2020, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.224; WoS Impact Factor: 2018 = 4.183 (2) - 2018=4.331 (5)
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