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Novel Antimicrobial Peptides Designed Using a Recurrent Neural Network Reduce Mortality in Experimental Sepsis

The search and development of new antibiotics is relevant due to widespread antibiotic resistance. One of the promising strategies is the de novo design of novel antimicrobial peptides. The amino acid sequences of 198 novel peptides were obtained using a generative long short-term memory recurrent n...

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Autores principales: Bolatchiev, Albert, Baturin, Vladimir, Shchetinin, Evgeny, Bolatchieva, Elizaveta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944797/
https://www.ncbi.nlm.nih.gov/pubmed/35326874
http://dx.doi.org/10.3390/antibiotics11030411
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author Bolatchiev, Albert
Baturin, Vladimir
Shchetinin, Evgeny
Bolatchieva, Elizaveta
author_facet Bolatchiev, Albert
Baturin, Vladimir
Shchetinin, Evgeny
Bolatchieva, Elizaveta
author_sort Bolatchiev, Albert
collection PubMed
description The search and development of new antibiotics is relevant due to widespread antibiotic resistance. One of the promising strategies is the de novo design of novel antimicrobial peptides. The amino acid sequences of 198 novel peptides were obtained using a generative long short-term memory recurrent neural network (LSTM RNN). To assess their antimicrobial effect, we synthesized five out of 198 generated peptides. The PEP-38 and PEP-137 peptides were active in vitro against carbapenem-resistant isolates of Klebsiella aerogenes and K. pneumoniae. PEP-137 was also active against Pseudomonas aeruginosa. The remaining three peptides (PEP-36, PEP-136 and PEP-174) showed no antibacterial effect. Then the effect of PEP-38 and PEP-137 (a single intraperitoneal administration of a 100 μg dose 30 min after infection) on animal survival in an experimental murine model of K. pneumoniae-induced sepsis was investigated. As a control, two groups of mice were used: one received sterile saline, and the other received inactive in vitro PEP-36 (a single 100 μg dose). The PEP-36 peptide was shown to provide the highest survival rate (66.7%). PEP-137 showed a survival rate of 50%. PEP-38 was found to be ineffective. The data obtained can be used to develop new antibacterial peptide drugs to combat antibiotic resistance.
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spelling pubmed-89447972022-03-25 Novel Antimicrobial Peptides Designed Using a Recurrent Neural Network Reduce Mortality in Experimental Sepsis Bolatchiev, Albert Baturin, Vladimir Shchetinin, Evgeny Bolatchieva, Elizaveta Antibiotics (Basel) Article The search and development of new antibiotics is relevant due to widespread antibiotic resistance. One of the promising strategies is the de novo design of novel antimicrobial peptides. The amino acid sequences of 198 novel peptides were obtained using a generative long short-term memory recurrent neural network (LSTM RNN). To assess their antimicrobial effect, we synthesized five out of 198 generated peptides. The PEP-38 and PEP-137 peptides were active in vitro against carbapenem-resistant isolates of Klebsiella aerogenes and K. pneumoniae. PEP-137 was also active against Pseudomonas aeruginosa. The remaining three peptides (PEP-36, PEP-136 and PEP-174) showed no antibacterial effect. Then the effect of PEP-38 and PEP-137 (a single intraperitoneal administration of a 100 μg dose 30 min after infection) on animal survival in an experimental murine model of K. pneumoniae-induced sepsis was investigated. As a control, two groups of mice were used: one received sterile saline, and the other received inactive in vitro PEP-36 (a single 100 μg dose). The PEP-36 peptide was shown to provide the highest survival rate (66.7%). PEP-137 showed a survival rate of 50%. PEP-38 was found to be ineffective. The data obtained can be used to develop new antibacterial peptide drugs to combat antibiotic resistance. MDPI 2022-03-18 /pmc/articles/PMC8944797/ /pubmed/35326874 http://dx.doi.org/10.3390/antibiotics11030411 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
Bolatchiev, Albert
Baturin, Vladimir
Shchetinin, Evgeny
Bolatchieva, Elizaveta
Novel Antimicrobial Peptides Designed Using a Recurrent Neural Network Reduce Mortality in Experimental Sepsis
title Novel Antimicrobial Peptides Designed Using a Recurrent Neural Network Reduce Mortality in Experimental Sepsis
title_full Novel Antimicrobial Peptides Designed Using a Recurrent Neural Network Reduce Mortality in Experimental Sepsis
title_fullStr Novel Antimicrobial Peptides Designed Using a Recurrent Neural Network Reduce Mortality in Experimental Sepsis
title_full_unstemmed Novel Antimicrobial Peptides Designed Using a Recurrent Neural Network Reduce Mortality in Experimental Sepsis
title_short Novel Antimicrobial Peptides Designed Using a Recurrent Neural Network Reduce Mortality in Experimental Sepsis
title_sort novel antimicrobial peptides designed using a recurrent neural network reduce mortality in experimental sepsis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944797/
https://www.ncbi.nlm.nih.gov/pubmed/35326874
http://dx.doi.org/10.3390/antibiotics11030411
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