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Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens

Host defense peptides (HDPs) represent an alternative way to address the emergence of antibiotic resistance. Crocodylians are interesting species for the study of these molecules because of their potent immune system, which confers high resistance to infection. Profile hidden Markov models were used...

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Autores principales: Santana, Felix L., Estrada, Karel, Alford, Morgan A., Wu, Bing C., Dostert, Melanie, Pedraz, Lucas, Akhoundsadegh, Noushin, Kalsi, Pavneet, Haney, Evan F., Straus, Suzana K., Corzo, Gerardo, Hancock, Robert E. W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686568/
https://www.ncbi.nlm.nih.gov/pubmed/36421248
http://dx.doi.org/10.3390/antibiotics11111603
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author Santana, Felix L.
Estrada, Karel
Alford, Morgan A.
Wu, Bing C.
Dostert, Melanie
Pedraz, Lucas
Akhoundsadegh, Noushin
Kalsi, Pavneet
Haney, Evan F.
Straus, Suzana K.
Corzo, Gerardo
Hancock, Robert E. W.
author_facet Santana, Felix L.
Estrada, Karel
Alford, Morgan A.
Wu, Bing C.
Dostert, Melanie
Pedraz, Lucas
Akhoundsadegh, Noushin
Kalsi, Pavneet
Haney, Evan F.
Straus, Suzana K.
Corzo, Gerardo
Hancock, Robert E. W.
author_sort Santana, Felix L.
collection PubMed
description Host defense peptides (HDPs) represent an alternative way to address the emergence of antibiotic resistance. Crocodylians are interesting species for the study of these molecules because of their potent immune system, which confers high resistance to infection. Profile hidden Markov models were used to screen the genomes of four crocodylian species for encoded cathelicidins and eighteen novel sequences were identified. Synthetic cathelicidins showed broad spectrum antimicrobial and antibiofilm activity against several clinically important antibiotic-resistant bacteria. In particular, the As-CATH8 cathelicidin showed potent in vitro activity profiles similar to the last-resort antibiotics vancomycin and polymyxin B. In addition, As-CATH8 demonstrated rapid killing of planktonic and biofilm cells, which correlated with its ability to cause cytoplasmic membrane depolarization and permeabilization as well as binding to DNA. As-CATH8 displayed greater antibiofilm activity than the human cathelicidin LL-37 against methicillin-resistant Staphylococcus aureus in a human organoid model of biofilm skin infection. Furthermore, As-CATH8 demonstrated strong antibacterial effects in a murine abscess model of high-density bacterial infections against clinical isolates of S. aureus and Acinetobacter baumannii, two of the most common bacterial species causing skin infections globally. Overall, this work expands the repertoire of cathelicidin peptides known in crocodylians, including one with considerable therapeutic promise for treating common skin infections.
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spelling pubmed-96865682022-11-25 Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens Santana, Felix L. Estrada, Karel Alford, Morgan A. Wu, Bing C. Dostert, Melanie Pedraz, Lucas Akhoundsadegh, Noushin Kalsi, Pavneet Haney, Evan F. Straus, Suzana K. Corzo, Gerardo Hancock, Robert E. W. Antibiotics (Basel) Article Host defense peptides (HDPs) represent an alternative way to address the emergence of antibiotic resistance. Crocodylians are interesting species for the study of these molecules because of their potent immune system, which confers high resistance to infection. Profile hidden Markov models were used to screen the genomes of four crocodylian species for encoded cathelicidins and eighteen novel sequences were identified. Synthetic cathelicidins showed broad spectrum antimicrobial and antibiofilm activity against several clinically important antibiotic-resistant bacteria. In particular, the As-CATH8 cathelicidin showed potent in vitro activity profiles similar to the last-resort antibiotics vancomycin and polymyxin B. In addition, As-CATH8 demonstrated rapid killing of planktonic and biofilm cells, which correlated with its ability to cause cytoplasmic membrane depolarization and permeabilization as well as binding to DNA. As-CATH8 displayed greater antibiofilm activity than the human cathelicidin LL-37 against methicillin-resistant Staphylococcus aureus in a human organoid model of biofilm skin infection. Furthermore, As-CATH8 demonstrated strong antibacterial effects in a murine abscess model of high-density bacterial infections against clinical isolates of S. aureus and Acinetobacter baumannii, two of the most common bacterial species causing skin infections globally. Overall, this work expands the repertoire of cathelicidin peptides known in crocodylians, including one with considerable therapeutic promise for treating common skin infections. MDPI 2022-11-11 /pmc/articles/PMC9686568/ /pubmed/36421248 http://dx.doi.org/10.3390/antibiotics11111603 Text en © 2022 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
Santana, Felix L.
Estrada, Karel
Alford, Morgan A.
Wu, Bing C.
Dostert, Melanie
Pedraz, Lucas
Akhoundsadegh, Noushin
Kalsi, Pavneet
Haney, Evan F.
Straus, Suzana K.
Corzo, Gerardo
Hancock, Robert E. W.
Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens
title Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens
title_full Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens
title_fullStr Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens
title_full_unstemmed Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens
title_short Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens
title_sort novel alligator cathelicidin as-cath8 demonstrates anti-infective activity against clinically relevant and crocodylian bacterial pathogens
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686568/
https://www.ncbi.nlm.nih.gov/pubmed/36421248
http://dx.doi.org/10.3390/antibiotics11111603
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