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...

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Main Authors: Roberto Vázquez, Sofía Blanco-Gañán, Susana Ruiz, Pedro García
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2021.660403/full
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spelling doaj-a3afe1e194c746bcab98cadd77c888402021-05-25T05:16:57ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-05-011210.3389/fmicb.2021.660403660403Mining of Gram-Negative Surface-Active Enzybiotic Candidates by Sequence-Based Calculation of Physicochemical PropertiesRoberto Vázquez0Roberto Vázquez1Sofía Blanco-Gañán2Susana Ruiz3Susana Ruiz4Pedro García5Pedro García6Departamento de Biotecnología Microbiana y de Plantas, Centro de Investigaciones Biológicas Margarita Salas (CIB-CSIC), Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, SpainDepartamento de Biotecnología Microbiana y de Plantas, Centro de Investigaciones Biológicas Margarita Salas (CIB-CSIC), Madrid, SpainDepartamento de Biotecnología Microbiana y de Plantas, Centro de Investigaciones Biológicas Margarita Salas (CIB-CSIC), Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, SpainDepartamento de Biotecnología Microbiana y de Plantas, Centro de Investigaciones Biológicas Margarita Salas (CIB-CSIC), Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, SpainPhage (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.https://www.frontiersin.org/articles/10.3389/fmicb.2021.660403/fulllysinsGram-negative bacteriabioinformatic analysisenzybioticsantimicrobialsenzyme mining
collection DOAJ
language English
format Article
sources DOAJ
author Roberto Vázquez
Roberto Vázquez
Sofía Blanco-Gañán
Susana Ruiz
Susana Ruiz
Pedro García
Pedro García
spellingShingle Roberto Vázquez
Roberto Vázquez
Sofía Blanco-Gañán
Susana Ruiz
Susana Ruiz
Pedro García
Pedro García
Mining of Gram-Negative Surface-Active Enzybiotic Candidates by Sequence-Based Calculation of Physicochemical Properties
Frontiers in Microbiology
lysins
Gram-negative bacteria
bioinformatic analysis
enzybiotics
antimicrobials
enzyme mining
author_facet Roberto Vázquez
Roberto Vázquez
Sofía Blanco-Gañán
Susana Ruiz
Susana Ruiz
Pedro García
Pedro García
author_sort Roberto Vázquez
title 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_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_sort mining of gram-negative surface-active enzybiotic candidates by sequence-based calculation of physicochemical properties
publisher Frontiers Media S.A.
series Frontiers in Microbiology
issn 1664-302X
publishDate 2021-05-01
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.
topic lysins
Gram-negative bacteria
bioinformatic analysis
enzybiotics
antimicrobials
enzyme mining
url https://www.frontiersin.org/articles/10.3389/fmicb.2021.660403/full
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