Antibacterial Activity of T22, a Specific Peptidic Ligand of the Tumoral Marker CXCR4

CXCR4 is a cytokine receptor used by HIV during cell attachment and infection. Overexpressed in the cancer stem cells of more than 20 human neoplasias, CXCR4 is a convenient antitumoral drug target. T22 is a polyphemusin-derived peptide and an effective CXCR4 ligand. Its highly selective CXCR4 bindi...

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Autores principales: Naroa Serna, José Vicente Carratalá, Oscar Conchillo-Solé, Carlos Martínez-Torró, Ugutz Unzueta, Ramón Mangues, Neus Ferrer-Miralles, Xavier Daura, Esther Vázquez, Antonio Villaverde
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:6ce775b1fd7147279d540e20658bd6772021-11-25T18:41:52ZAntibacterial Activity of T22, a Specific Peptidic Ligand of the Tumoral Marker CXCR410.3390/pharmaceutics131119221999-4923https://doaj.org/article/6ce775b1fd7147279d540e20658bd6772021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1922https://doaj.org/toc/1999-4923CXCR4 is a cytokine receptor used by HIV during cell attachment and infection. Overexpressed in the cancer stem cells of more than 20 human neoplasias, CXCR4 is a convenient antitumoral drug target. T22 is a polyphemusin-derived peptide and an effective CXCR4 ligand. Its highly selective CXCR4 binding can be exploited as an agent for the cell-targeted delivery and internalization of associated antitumor drugs. Sharing chemical and structural traits with antimicrobial peptides (AMPs), the capability of T22 as an antibacterial agent remains unexplored. Here, we have detected T22-associated antimicrobial activity and biofilm formation inhibition over <i>Escherichia coli</i>, <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>, in a spectrum broader than the reference AMP GWH1. In contrast to GWH1, T22 shows neither cytotoxicity over mammalian cells nor hemolytic activity and is active when displayed on protein-only nanoparticles through genetic fusion. Under the pushing need for novel antimicrobial agents, the discovery of T22 as an AMP is particularly appealing, not only as its mere addition to the expanding catalogue of antibacterial drugs. The recognized clinical uses of T22 might allow its combined and multivalent application in complex clinical conditions, such as colorectal cancer, that might benefit from the synchronous destruction of cancer stem cells and local bacterial biofilms.Naroa SernaJosé Vicente CarrataláOscar Conchillo-SoléCarlos Martínez-TorróUgutz UnzuetaRamón ManguesNeus Ferrer-MirallesXavier DauraEsther VázquezAntonio VillaverdeMDPI AGarticleantimicrobial peptidesnanoparticlesfusion proteinsinhibition of biofilm formationmultivalent drugsPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1922, p 1922 (2021)
institution DOAJ
collection DOAJ
language EN
topic antimicrobial peptides
nanoparticles
fusion proteins
inhibition of biofilm formation
multivalent drugs
Pharmacy and materia medica
RS1-441
spellingShingle antimicrobial peptides
nanoparticles
fusion proteins
inhibition of biofilm formation
multivalent drugs
Pharmacy and materia medica
RS1-441
Naroa Serna
José Vicente Carratalá
Oscar Conchillo-Solé
Carlos Martínez-Torró
Ugutz Unzueta
Ramón Mangues
Neus Ferrer-Miralles
Xavier Daura
Esther Vázquez
Antonio Villaverde
Antibacterial Activity of T22, a Specific Peptidic Ligand of the Tumoral Marker CXCR4
description CXCR4 is a cytokine receptor used by HIV during cell attachment and infection. Overexpressed in the cancer stem cells of more than 20 human neoplasias, CXCR4 is a convenient antitumoral drug target. T22 is a polyphemusin-derived peptide and an effective CXCR4 ligand. Its highly selective CXCR4 binding can be exploited as an agent for the cell-targeted delivery and internalization of associated antitumor drugs. Sharing chemical and structural traits with antimicrobial peptides (AMPs), the capability of T22 as an antibacterial agent remains unexplored. Here, we have detected T22-associated antimicrobial activity and biofilm formation inhibition over <i>Escherichia coli</i>, <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>, in a spectrum broader than the reference AMP GWH1. In contrast to GWH1, T22 shows neither cytotoxicity over mammalian cells nor hemolytic activity and is active when displayed on protein-only nanoparticles through genetic fusion. Under the pushing need for novel antimicrobial agents, the discovery of T22 as an AMP is particularly appealing, not only as its mere addition to the expanding catalogue of antibacterial drugs. The recognized clinical uses of T22 might allow its combined and multivalent application in complex clinical conditions, such as colorectal cancer, that might benefit from the synchronous destruction of cancer stem cells and local bacterial biofilms.
format article
author Naroa Serna
José Vicente Carratalá
Oscar Conchillo-Solé
Carlos Martínez-Torró
Ugutz Unzueta
Ramón Mangues
Neus Ferrer-Miralles
Xavier Daura
Esther Vázquez
Antonio Villaverde
author_facet Naroa Serna
José Vicente Carratalá
Oscar Conchillo-Solé
Carlos Martínez-Torró
Ugutz Unzueta
Ramón Mangues
Neus Ferrer-Miralles
Xavier Daura
Esther Vázquez
Antonio Villaverde
author_sort Naroa Serna
title Antibacterial Activity of T22, a Specific Peptidic Ligand of the Tumoral Marker CXCR4
title_short Antibacterial Activity of T22, a Specific Peptidic Ligand of the Tumoral Marker CXCR4
title_full Antibacterial Activity of T22, a Specific Peptidic Ligand of the Tumoral Marker CXCR4
title_fullStr Antibacterial Activity of T22, a Specific Peptidic Ligand of the Tumoral Marker CXCR4
title_full_unstemmed Antibacterial Activity of T22, a Specific Peptidic Ligand of the Tumoral Marker CXCR4
title_sort antibacterial activity of t22, a specific peptidic ligand of the tumoral marker cxcr4
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/6ce775b1fd7147279d540e20658bd677
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