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Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens

The extremely rapid spread of multiple-antibiotic resistance among Gram-negative pathogens threatens to move humankind into the so-called “post-antibiotic era” in which the most efficient and safe antibiotics will not work. Bacteriophage lysins represent promising alternatives to antibiotics, as the...

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Autores principales: Antonova, Nataliia P., Vasina, Daria V., Lendel, Anastasiya M., Usachev, Evgeny V., Makarov, Valentine V., Gintsburg, Alexander L., Tkachuk, Artem P., Gushchin, Vladimir A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466606/
https://www.ncbi.nlm.nih.gov/pubmed/30901901
http://dx.doi.org/10.3390/v11030284
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author Antonova, Nataliia P.
Vasina, Daria V.
Lendel, Anastasiya M.
Usachev, Evgeny V.
Makarov, Valentine V.
Gintsburg, Alexander L.
Tkachuk, Artem P.
Gushchin, Vladimir A.
author_facet Antonova, Nataliia P.
Vasina, Daria V.
Lendel, Anastasiya M.
Usachev, Evgeny V.
Makarov, Valentine V.
Gintsburg, Alexander L.
Tkachuk, Artem P.
Gushchin, Vladimir A.
author_sort Antonova, Nataliia P.
collection PubMed
description The extremely rapid spread of multiple-antibiotic resistance among Gram-negative pathogens threatens to move humankind into the so-called “post-antibiotic era” in which the most efficient and safe antibiotics will not work. Bacteriophage lysins represent promising alternatives to antibiotics, as they are capable of digesting bacterial cell wall peptidoglycans to promote their osmotic lysis. However, relatively little is known regarding the spectrum of lysin bactericidal activity against Gram-negative bacteria. In this study, we present the results of in vitro activity assays of three putative and newly cloned Myoviridae bacteriophage endolysins (LysAm24, LysECD7, and LysSi3). The chosen proteins represent lysins with diverse domain organization (single-domain vs. two-domain) and different predicted mechanisms of action (lysozyme vs. peptidase). The enzymes were purified, and their properties were characterized. The enzymes were tested against a panel of Gram-negative clinical bacterial isolates comprising all Gram-negative representatives of the ESKAPE group. Despite exhibiting different structural organizations, all of the assayed lysins were shown to be capable of lysing Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Salmonella typhi strains. Less than 50 μg/mL was enough to eradicate growing cells over more than five orders of magnitude. Thus, LysAm24, LysECD7, and LysSi3 represent promising therapeutic agents for drug development.
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spelling pubmed-64666062019-04-18 Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens Antonova, Nataliia P. Vasina, Daria V. Lendel, Anastasiya M. Usachev, Evgeny V. Makarov, Valentine V. Gintsburg, Alexander L. Tkachuk, Artem P. Gushchin, Vladimir A. Viruses Article The extremely rapid spread of multiple-antibiotic resistance among Gram-negative pathogens threatens to move humankind into the so-called “post-antibiotic era” in which the most efficient and safe antibiotics will not work. Bacteriophage lysins represent promising alternatives to antibiotics, as they are capable of digesting bacterial cell wall peptidoglycans to promote their osmotic lysis. However, relatively little is known regarding the spectrum of lysin bactericidal activity against Gram-negative bacteria. In this study, we present the results of in vitro activity assays of three putative and newly cloned Myoviridae bacteriophage endolysins (LysAm24, LysECD7, and LysSi3). The chosen proteins represent lysins with diverse domain organization (single-domain vs. two-domain) and different predicted mechanisms of action (lysozyme vs. peptidase). The enzymes were purified, and their properties were characterized. The enzymes were tested against a panel of Gram-negative clinical bacterial isolates comprising all Gram-negative representatives of the ESKAPE group. Despite exhibiting different structural organizations, all of the assayed lysins were shown to be capable of lysing Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Salmonella typhi strains. Less than 50 μg/mL was enough to eradicate growing cells over more than five orders of magnitude. Thus, LysAm24, LysECD7, and LysSi3 represent promising therapeutic agents for drug development. MDPI 2019-03-21 /pmc/articles/PMC6466606/ /pubmed/30901901 http://dx.doi.org/10.3390/v11030284 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Antonova, Nataliia P.
Vasina, Daria V.
Lendel, Anastasiya M.
Usachev, Evgeny V.
Makarov, Valentine V.
Gintsburg, Alexander L.
Tkachuk, Artem P.
Gushchin, Vladimir A.
Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens
title Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens
title_full Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens
title_fullStr Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens
title_full_unstemmed Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens
title_short Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens
title_sort broad bactericidal activity of the myoviridae bacteriophage lysins lysam24, lysecd7, and lyssi3 against gram-negative eskape pathogens
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466606/
https://www.ncbi.nlm.nih.gov/pubmed/30901901
http://dx.doi.org/10.3390/v11030284
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