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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...

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Autores principales: Shah, Sanket, Das, Ritam, Chavan, Bhakti, Bajpai, Urmi, Hanif, Sarmad, Ahmed, Syed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
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.
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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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