Cargando…

Mining of Gram-Negative Surface-Active Enzybiotic Candidates by Sequence-Based Calculation of Physicochemical Properties

Phage (endo)lysins are nowadays one of the most promising ways out of the current antibiotic resistance crisis. Either as sole therapeutics or as a complement to common antibiotic chemotherapy, lysins are already entering late clinical phases to get regulatory agencies’ authorization. Even the old p...

Descripción completa

Detalles Bibliográficos
Autores principales: Vázquez, Roberto, Blanco-Gañán, Sofía, Ruiz, Susana, García, Pedro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185167/
https://www.ncbi.nlm.nih.gov/pubmed/34113327
http://dx.doi.org/10.3389/fmicb.2021.660403
_version_ 1783704730376077312
author Vázquez, Roberto
Blanco-Gañán, Sofía
Ruiz, Susana
García, Pedro
author_facet Vázquez, Roberto
Blanco-Gañán, Sofía
Ruiz, Susana
García, Pedro
author_sort Vázquez, Roberto
collection PubMed
description Phage (endo)lysins are nowadays one of the most promising ways out of the current antibiotic resistance crisis. Either as sole therapeutics or as a complement to common antibiotic chemotherapy, lysins are already entering late clinical phases to get regulatory agencies’ authorization. Even the old paradigm of the inability of lysins to attack Gram-negative bacteria from without has already been overcome in a variety of ways: either by engineering approaches or investigating the natural mechanisms by which some wild-type lysins are able to interact with the bacterial surface. Such inherent ability of some lysins has been linked to antimicrobial peptide (AMP)-like regions, which are, on their own, a significant source for novel antimicrobials. Currently, though, many of the efforts for searching novel lysin-based antimicrobial candidates rely on experimental screenings. In this work, we have bioinformatically analyzed the C-terminal end of a collection of lysins from phages infecting the Gram-negative genus Pseudomonas. Through the computation of physicochemical properties, the probability of such regions to be an AMP was estimated by means of a predictive k-nearest neighbors (kNN) model. This way, a subset of putatively membrane-interacting lysins was obtained from the original database. Two of such candidates (named Pae87 and Ppl65) were prospectively tested in terms of muralytic, bacteriolytic, and bactericidal activity. Both of them were found to possess an activity against Pseudomonas aeruginosa and other Gram-negative bacterial pathogens, implying that the prediction of AMP-like regions could be a useful approach toward the mining of phage lysins to design and develop antimicrobials or antimicrobial parts for further engineering.
format Online
Article
Text
id pubmed-8185167
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-81851672021-06-09 Mining of Gram-Negative Surface-Active Enzybiotic Candidates by Sequence-Based Calculation of Physicochemical Properties Vázquez, Roberto Blanco-Gañán, Sofía Ruiz, Susana García, Pedro Front Microbiol Microbiology Phage (endo)lysins are nowadays one of the most promising ways out of the current antibiotic resistance crisis. Either as sole therapeutics or as a complement to common antibiotic chemotherapy, lysins are already entering late clinical phases to get regulatory agencies’ authorization. Even the old paradigm of the inability of lysins to attack Gram-negative bacteria from without has already been overcome in a variety of ways: either by engineering approaches or investigating the natural mechanisms by which some wild-type lysins are able to interact with the bacterial surface. Such inherent ability of some lysins has been linked to antimicrobial peptide (AMP)-like regions, which are, on their own, a significant source for novel antimicrobials. Currently, though, many of the efforts for searching novel lysin-based antimicrobial candidates rely on experimental screenings. In this work, we have bioinformatically analyzed the C-terminal end of a collection of lysins from phages infecting the Gram-negative genus Pseudomonas. Through the computation of physicochemical properties, the probability of such regions to be an AMP was estimated by means of a predictive k-nearest neighbors (kNN) model. This way, a subset of putatively membrane-interacting lysins was obtained from the original database. Two of such candidates (named Pae87 and Ppl65) were prospectively tested in terms of muralytic, bacteriolytic, and bactericidal activity. Both of them were found to possess an activity against Pseudomonas aeruginosa and other Gram-negative bacterial pathogens, implying that the prediction of AMP-like regions could be a useful approach toward the mining of phage lysins to design and develop antimicrobials or antimicrobial parts for further engineering. Frontiers Media S.A. 2021-05-25 /pmc/articles/PMC8185167/ /pubmed/34113327 http://dx.doi.org/10.3389/fmicb.2021.660403 Text en Copyright © 2021 Vázquez, Blanco-Gañán, Ruiz and García. 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
Vázquez, Roberto
Blanco-Gañán, Sofía
Ruiz, Susana
García, Pedro
Mining of Gram-Negative Surface-Active Enzybiotic Candidates by Sequence-Based Calculation of Physicochemical Properties
title Mining of Gram-Negative Surface-Active Enzybiotic Candidates by Sequence-Based Calculation of Physicochemical Properties
title_full Mining of Gram-Negative Surface-Active Enzybiotic Candidates by Sequence-Based Calculation of Physicochemical Properties
title_fullStr Mining of Gram-Negative Surface-Active Enzybiotic Candidates by Sequence-Based Calculation of Physicochemical Properties
title_full_unstemmed Mining of Gram-Negative Surface-Active Enzybiotic Candidates by Sequence-Based Calculation of Physicochemical Properties
title_short Mining of Gram-Negative Surface-Active Enzybiotic Candidates by Sequence-Based Calculation of Physicochemical Properties
title_sort mining of gram-negative surface-active enzybiotic candidates by sequence-based calculation of physicochemical properties
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185167/
https://www.ncbi.nlm.nih.gov/pubmed/34113327
http://dx.doi.org/10.3389/fmicb.2021.660403
work_keys_str_mv AT vazquezroberto miningofgramnegativesurfaceactiveenzybioticcandidatesbysequencebasedcalculationofphysicochemicalproperties
AT blancoganansofia miningofgramnegativesurfaceactiveenzybioticcandidatesbysequencebasedcalculationofphysicochemicalproperties
AT ruizsusana miningofgramnegativesurfaceactiveenzybioticcandidatesbysequencebasedcalculationofphysicochemicalproperties
AT garciapedro miningofgramnegativesurfaceactiveenzybioticcandidatesbysequencebasedcalculationofphysicochemicalproperties