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Beyond antibiotics: phage-encoded lysins against Gram-negative pathogens
Antibiotics remain the frontline agents for treating deadly bacterial pathogens. However, the indiscriminate use of these valuable agents has led to an alarming rise in AMR. The antibiotic pipeline is insufficient to tackle the AMR threat, especially with respect to the WHO critical category of prio...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542408/ https://www.ncbi.nlm.nih.gov/pubmed/37789862 http://dx.doi.org/10.3389/fmicb.2023.1170418 |
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author | Shah, Sanket Das, Ritam Chavan, Bhakti Bajpai, Urmi Hanif, Sarmad Ahmed, Syed |
author_facet | Shah, Sanket Das, Ritam Chavan, Bhakti Bajpai, Urmi Hanif, Sarmad Ahmed, Syed |
author_sort | Shah, Sanket |
collection | PubMed |
description | Antibiotics remain the frontline agents for treating deadly bacterial pathogens. However, the indiscriminate use of these valuable agents has led to an alarming rise in AMR. The antibiotic pipeline is insufficient to tackle the AMR threat, especially with respect to the WHO critical category of priority Gram-negative pathogens, which have become a serious problem as nosocomial and community infections and pose a threat globally. The AMR pandemic requires solutions that provide novel antibacterial agents that are not only effective but against which bacteria are less likely to gain resistance. In this regard, natural or engineered phage-encoded lysins (enzybiotics) armed with numerous features represent an attractive alternative to the currently available antibiotics. Several lysins have exhibited promising efficacy and safety against Gram-positive pathogens, with some in late stages of clinical development and some commercially available. However, in the case of Gram-negative bacteria, the outer membrane acts as a formidable barrier; hence, lysins are often used in combination with OMPs or engineered to overcome the outer membrane barrier. In this review, we have briefly explained AMR and the initiatives taken by different organizations globally to tackle the AMR threat at different levels. We bring forth the promising potential and challenges of lysins, focusing on the WHO critical category of priority Gram-negative bacteria and lysins under investigation for these pathogens, along with the challenges associated with developing them as therapeutics within the existing regulatory framework. |
format | Online Article Text |
id | pubmed-10542408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105424082023-10-03 Beyond antibiotics: phage-encoded lysins against Gram-negative pathogens Shah, Sanket Das, Ritam Chavan, Bhakti Bajpai, Urmi Hanif, Sarmad Ahmed, Syed Front Microbiol Microbiology Antibiotics remain the frontline agents for treating deadly bacterial pathogens. However, the indiscriminate use of these valuable agents has led to an alarming rise in AMR. The antibiotic pipeline is insufficient to tackle the AMR threat, especially with respect to the WHO critical category of priority Gram-negative pathogens, which have become a serious problem as nosocomial and community infections and pose a threat globally. The AMR pandemic requires solutions that provide novel antibacterial agents that are not only effective but against which bacteria are less likely to gain resistance. In this regard, natural or engineered phage-encoded lysins (enzybiotics) armed with numerous features represent an attractive alternative to the currently available antibiotics. Several lysins have exhibited promising efficacy and safety against Gram-positive pathogens, with some in late stages of clinical development and some commercially available. However, in the case of Gram-negative bacteria, the outer membrane acts as a formidable barrier; hence, lysins are often used in combination with OMPs or engineered to overcome the outer membrane barrier. In this review, we have briefly explained AMR and the initiatives taken by different organizations globally to tackle the AMR threat at different levels. We bring forth the promising potential and challenges of lysins, focusing on the WHO critical category of priority Gram-negative bacteria and lysins under investigation for these pathogens, along with the challenges associated with developing them as therapeutics within the existing regulatory framework. Frontiers Media S.A. 2023-09-08 /pmc/articles/PMC10542408/ /pubmed/37789862 http://dx.doi.org/10.3389/fmicb.2023.1170418 Text en Copyright © 2023 Shah, Das, Chavan, Bajpai, Hanif and Ahmed. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Shah, Sanket Das, Ritam Chavan, Bhakti Bajpai, Urmi Hanif, Sarmad Ahmed, Syed Beyond antibiotics: phage-encoded lysins against Gram-negative pathogens |
title | Beyond antibiotics: phage-encoded lysins against Gram-negative pathogens |
title_full | Beyond antibiotics: phage-encoded lysins against Gram-negative pathogens |
title_fullStr | Beyond antibiotics: phage-encoded lysins against Gram-negative pathogens |
title_full_unstemmed | Beyond antibiotics: phage-encoded lysins against Gram-negative pathogens |
title_short | Beyond antibiotics: phage-encoded lysins against Gram-negative pathogens |
title_sort | beyond antibiotics: phage-encoded lysins against gram-negative pathogens |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542408/ https://www.ncbi.nlm.nih.gov/pubmed/37789862 http://dx.doi.org/10.3389/fmicb.2023.1170418 |
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