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Antimicrobial Random Peptide Mixtures Eradicate Acinetobacter baumannii Biofilms and Inhibit Mouse Models of Infection
Antibiotic resistance is one of the greatest crises in human medicine. Increased incidents of antibiotic resistance are linked to clinical overuse and overreliance on antibiotics. Among the ESKAPE pathogens, Acinetobacter baumannii, especially carbapenem-resistant isolates, has emerged as a signific...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944503/ https://www.ncbi.nlm.nih.gov/pubmed/35326876 http://dx.doi.org/10.3390/antibiotics11030413 |
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author | Caraway, Hannah E. Lau, Jonathan Z. Maron, Bar Oh, Myung Whan Belo, Yael Brill, Aya Malach, Einav Ismail, Nahed Hayouka, Zvi Lau, Gee W. |
author_facet | Caraway, Hannah E. Lau, Jonathan Z. Maron, Bar Oh, Myung Whan Belo, Yael Brill, Aya Malach, Einav Ismail, Nahed Hayouka, Zvi Lau, Gee W. |
author_sort | Caraway, Hannah E. |
collection | PubMed |
description | Antibiotic resistance is one of the greatest crises in human medicine. Increased incidents of antibiotic resistance are linked to clinical overuse and overreliance on antibiotics. Among the ESKAPE pathogens, Acinetobacter baumannii, especially carbapenem-resistant isolates, has emerged as a significant threat in the context of blood, urinary tract, lung, and wound infections. Therefore, new approaches that limit the emergence of antibiotic resistant A. baumannii are urgently needed. Recently, we have shown that random peptide mixtures (RPMs) are an attractive alternative class of drugs to antibiotics with strong safety and pharmacokinetic profiles. RPMs are antimicrobial peptide mixtures produced by incorporating two amino acids at each coupling step, rendering them extremely diverse but still defined in their overall composition, chain length, and stereochemistry. The extreme diversity of RPMs may prevent bacteria from evolving resistance rapidly. Here, we demonstrated that RPMs rapidly and efficiently kill different strains of A. baumannii, inhibit biofilm formation, and disrupt mature biofilms. Importantly, RPMs attenuated bacterial burden in mouse models of acute pneumonia and soft tissue infection and significantly reduced mouse mortality during sepsis. Collectively, our results demonstrate RPMs have the potential to be used as powerful therapeutics against antibiotic-resistant A. baumannii. |
format | Online Article Text |
id | pubmed-8944503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89445032022-03-25 Antimicrobial Random Peptide Mixtures Eradicate Acinetobacter baumannii Biofilms and Inhibit Mouse Models of Infection Caraway, Hannah E. Lau, Jonathan Z. Maron, Bar Oh, Myung Whan Belo, Yael Brill, Aya Malach, Einav Ismail, Nahed Hayouka, Zvi Lau, Gee W. Antibiotics (Basel) Article Antibiotic resistance is one of the greatest crises in human medicine. Increased incidents of antibiotic resistance are linked to clinical overuse and overreliance on antibiotics. Among the ESKAPE pathogens, Acinetobacter baumannii, especially carbapenem-resistant isolates, has emerged as a significant threat in the context of blood, urinary tract, lung, and wound infections. Therefore, new approaches that limit the emergence of antibiotic resistant A. baumannii are urgently needed. Recently, we have shown that random peptide mixtures (RPMs) are an attractive alternative class of drugs to antibiotics with strong safety and pharmacokinetic profiles. RPMs are antimicrobial peptide mixtures produced by incorporating two amino acids at each coupling step, rendering them extremely diverse but still defined in their overall composition, chain length, and stereochemistry. The extreme diversity of RPMs may prevent bacteria from evolving resistance rapidly. Here, we demonstrated that RPMs rapidly and efficiently kill different strains of A. baumannii, inhibit biofilm formation, and disrupt mature biofilms. Importantly, RPMs attenuated bacterial burden in mouse models of acute pneumonia and soft tissue infection and significantly reduced mouse mortality during sepsis. Collectively, our results demonstrate RPMs have the potential to be used as powerful therapeutics against antibiotic-resistant A. baumannii. MDPI 2022-03-19 /pmc/articles/PMC8944503/ /pubmed/35326876 http://dx.doi.org/10.3390/antibiotics11030413 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 Caraway, Hannah E. Lau, Jonathan Z. Maron, Bar Oh, Myung Whan Belo, Yael Brill, Aya Malach, Einav Ismail, Nahed Hayouka, Zvi Lau, Gee W. Antimicrobial Random Peptide Mixtures Eradicate Acinetobacter baumannii Biofilms and Inhibit Mouse Models of Infection |
title | Antimicrobial Random Peptide Mixtures Eradicate Acinetobacter baumannii Biofilms and Inhibit Mouse Models of Infection |
title_full | Antimicrobial Random Peptide Mixtures Eradicate Acinetobacter baumannii Biofilms and Inhibit Mouse Models of Infection |
title_fullStr | Antimicrobial Random Peptide Mixtures Eradicate Acinetobacter baumannii Biofilms and Inhibit Mouse Models of Infection |
title_full_unstemmed | Antimicrobial Random Peptide Mixtures Eradicate Acinetobacter baumannii Biofilms and Inhibit Mouse Models of Infection |
title_short | Antimicrobial Random Peptide Mixtures Eradicate Acinetobacter baumannii Biofilms and Inhibit Mouse Models of Infection |
title_sort | antimicrobial random peptide mixtures eradicate acinetobacter baumannii biofilms and inhibit mouse models of infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944503/ https://www.ncbi.nlm.nih.gov/pubmed/35326876 http://dx.doi.org/10.3390/antibiotics11030413 |
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