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Testing Antimicrobial Properties of Human Lactoferrin-Derived Fragments

Lactoferrin, an iron-binding glycoprotein, plays a significant role in the innate immune system, with antibacterial, antivirial, antifungal, anticancer, antioxidant and immunomodulatory functions reported. It is worth emphasizing that not only the whole protein but also its derived fragments possess...

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Autores principales: Ostrówka, Michał, Duda-Madej, Anna, Pietluch, Filip, Mackiewicz, Paweł, Gagat, Przemysław
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342102/
https://www.ncbi.nlm.nih.gov/pubmed/37445717
http://dx.doi.org/10.3390/ijms241310529
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author Ostrówka, Michał
Duda-Madej, Anna
Pietluch, Filip
Mackiewicz, Paweł
Gagat, Przemysław
author_facet Ostrówka, Michał
Duda-Madej, Anna
Pietluch, Filip
Mackiewicz, Paweł
Gagat, Przemysław
author_sort Ostrówka, Michał
collection PubMed
description Lactoferrin, an iron-binding glycoprotein, plays a significant role in the innate immune system, with antibacterial, antivirial, antifungal, anticancer, antioxidant and immunomodulatory functions reported. It is worth emphasizing that not only the whole protein but also its derived fragments possess antimicrobial peptide (AMP) activity. Using AmpGram, a top-performing AMP classifier, we generated three novel human lactoferrin (hLF) fragments: hLF 397-412, hLF 448-464 and hLF 668-683, predicted with high probability as AMPs. For comparative studies, we included hLF 1-11, previously confirmed to kill some bacteria. With the four peptides, we treated three Gram-negative and three Gram-positive bacterial strains. Our results indicate that none of the three new lactoferrin fragments have antimicrobial properties for the bacteria tested, but hLF 1-11 was lethal against Pseudomonas aeruginosa. The addition of serine protease inhibitors with the hLF fragments did not enhance their activity, except for hLF 1-11 against P. aeruginosa, which MIC dropped from 128 to 64 µg/mL. Furthermore, we investigated the impact of EDTA with/without serine protease inhibitors and the hLF peptides on selected bacteria. We stress the importance of reporting non-AMP sequences for the development of next-generation AMP prediction models, which suffer from the lack of experimentally validated negative dataset for training and benchmarking.
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spelling pubmed-103421022023-07-14 Testing Antimicrobial Properties of Human Lactoferrin-Derived Fragments Ostrówka, Michał Duda-Madej, Anna Pietluch, Filip Mackiewicz, Paweł Gagat, Przemysław Int J Mol Sci Article Lactoferrin, an iron-binding glycoprotein, plays a significant role in the innate immune system, with antibacterial, antivirial, antifungal, anticancer, antioxidant and immunomodulatory functions reported. It is worth emphasizing that not only the whole protein but also its derived fragments possess antimicrobial peptide (AMP) activity. Using AmpGram, a top-performing AMP classifier, we generated three novel human lactoferrin (hLF) fragments: hLF 397-412, hLF 448-464 and hLF 668-683, predicted with high probability as AMPs. For comparative studies, we included hLF 1-11, previously confirmed to kill some bacteria. With the four peptides, we treated three Gram-negative and three Gram-positive bacterial strains. Our results indicate that none of the three new lactoferrin fragments have antimicrobial properties for the bacteria tested, but hLF 1-11 was lethal against Pseudomonas aeruginosa. The addition of serine protease inhibitors with the hLF fragments did not enhance their activity, except for hLF 1-11 against P. aeruginosa, which MIC dropped from 128 to 64 µg/mL. Furthermore, we investigated the impact of EDTA with/without serine protease inhibitors and the hLF peptides on selected bacteria. We stress the importance of reporting non-AMP sequences for the development of next-generation AMP prediction models, which suffer from the lack of experimentally validated negative dataset for training and benchmarking. MDPI 2023-06-23 /pmc/articles/PMC10342102/ /pubmed/37445717 http://dx.doi.org/10.3390/ijms241310529 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ostrówka, Michał
Duda-Madej, Anna
Pietluch, Filip
Mackiewicz, Paweł
Gagat, Przemysław
Testing Antimicrobial Properties of Human Lactoferrin-Derived Fragments
title Testing Antimicrobial Properties of Human Lactoferrin-Derived Fragments
title_full Testing Antimicrobial Properties of Human Lactoferrin-Derived Fragments
title_fullStr Testing Antimicrobial Properties of Human Lactoferrin-Derived Fragments
title_full_unstemmed Testing Antimicrobial Properties of Human Lactoferrin-Derived Fragments
title_short Testing Antimicrobial Properties of Human Lactoferrin-Derived Fragments
title_sort testing antimicrobial properties of human lactoferrin-derived fragments
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342102/
https://www.ncbi.nlm.nih.gov/pubmed/37445717
http://dx.doi.org/10.3390/ijms241310529
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