LYZ2-SH3b as a novel and efficient enzybiotic against methicillin-resistant Staphylococcus aureus.
Enzybiotic
Exolysin
MRSA
SH3b domain
Staphylococcus aureus
Journal
BMC microbiology
ISSN: 1471-2180
Titre abrégé: BMC Microbiol
Pays: England
ID NLM: 100966981
Informations de publication
Date de publication:
13 09 2023
13 09 2023
Historique:
received:
12
01
2023
accepted:
04
09
2023
medline:
15
9
2023
pubmed:
14
9
2023
entrez:
13
9
2023
Statut:
epublish
Résumé
Enzybiotics are promising alternatives to conventional antibiotics for drug-resistant infections. Exolysins, as a class of enzybiotics, show antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA). This study evaluated a novel exolysin containing an SH3b domain for its antibacterial activity against MRSA. This study designed a chimeric exolysin by fusing the Cell-binding domain (SH3b) from Lysostaphin with the lytic domain (LYZ2) from the gp61 enzyme. Subsequently, LYZ2-SH3b was cloned and expressed in Escherichia coli (E. coli). Finally, the antibacterial effects of LYZ2-SH3b compared with LYZ2 and vancomycin against reference and clinical isolates of MRSA were measured using the disc diffusion method, the minimal inhibitory concentration (MIC), and the minimal bactericidal concentration (MBC) assays. Analysis of bioinformatics showed that LYZ2-SH3b was stable, soluble, and non-allergenic. Protein purification was performed with a 0.8 mg/ml yield for LYZ2-SH3b. The plate lysis assay results indicated that, at the same concentrations, LYZ2-SH3b has a more inhibitory effect than LYZ2. The MICs of LYZ2 were 4 µg/mL (ATCC 43,300) and 8 µg/mL (clinical isolate ST239), whereas, for LYZ2-SH3b, they were 2 µg/mL (ATCC 43,300) and 4 µg/mL (clinical isolate ST239). This suggests a higher efficiency of LYZ2-SH3b compared to LYZ2. Furthermore, the MBCs of LYZ2 were 4 µg/mL (ATCC 43,300) and 8 µg/mL (clinical isolate ST239), whereas, for LYZ2-SH3b, they were 2 µg/mL (ATCC 43,300) and 4 µg/mL (clinical isolate ST239), thus confirming the superior lytic activity of LYZ2-SH3b over LYZ2. The study suggests that phage endolysins, such as LYZ2-SH3b, may represent a promising new approach to treating MRSA infections, particularly in cases where antibiotic resistance is a concern. But further studies are needed.
Sections du résumé
BACKGROUND
Enzybiotics are promising alternatives to conventional antibiotics for drug-resistant infections. Exolysins, as a class of enzybiotics, show antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA). This study evaluated a novel exolysin containing an SH3b domain for its antibacterial activity against MRSA.
METHODS
This study designed a chimeric exolysin by fusing the Cell-binding domain (SH3b) from Lysostaphin with the lytic domain (LYZ2) from the gp61 enzyme. Subsequently, LYZ2-SH3b was cloned and expressed in Escherichia coli (E. coli). Finally, the antibacterial effects of LYZ2-SH3b compared with LYZ2 and vancomycin against reference and clinical isolates of MRSA were measured using the disc diffusion method, the minimal inhibitory concentration (MIC), and the minimal bactericidal concentration (MBC) assays.
RESULTS
Analysis of bioinformatics showed that LYZ2-SH3b was stable, soluble, and non-allergenic. Protein purification was performed with a 0.8 mg/ml yield for LYZ2-SH3b. The plate lysis assay results indicated that, at the same concentrations, LYZ2-SH3b has a more inhibitory effect than LYZ2. The MICs of LYZ2 were 4 µg/mL (ATCC 43,300) and 8 µg/mL (clinical isolate ST239), whereas, for LYZ2-SH3b, they were 2 µg/mL (ATCC 43,300) and 4 µg/mL (clinical isolate ST239). This suggests a higher efficiency of LYZ2-SH3b compared to LYZ2. Furthermore, the MBCs of LYZ2 were 4 µg/mL (ATCC 43,300) and 8 µg/mL (clinical isolate ST239), whereas, for LYZ2-SH3b, they were 2 µg/mL (ATCC 43,300) and 4 µg/mL (clinical isolate ST239), thus confirming the superior lytic activity of LYZ2-SH3b over LYZ2.
CONCLUSIONS
The study suggests that phage endolysins, such as LYZ2-SH3b, may represent a promising new approach to treating MRSA infections, particularly in cases where antibiotic resistance is a concern. But further studies are needed.
Identifiants
pubmed: 37704938
doi: 10.1186/s12866-023-03002-9
pii: 10.1186/s12866-023-03002-9
pmc: PMC10500863
doi:
Substances chimiques
Anti-Bacterial Agents
0
Vancomycin
6Q205EH1VU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
257Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
Références
Front Microbiol. 2021 Sep 14;12:723834
pubmed: 34594314
Viruses. 2012 Dec;4(12):3316-35
pubmed: 23342361
Bacteriophage. 2015 Jun 23;5(3):e1062590
pubmed: 26442196
Appl Environ Microbiol. 2012 Apr;78(7):2241-8
pubmed: 22267667
Viruses. 2018 May 25;10(6):
pubmed: 29799482
Front Cell Infect Microbiol. 2021 Apr 15;11:668430
pubmed: 33937105
Viruses. 2021 Apr 15;13(4):
pubmed: 33920965
Microbiol Res. 2016 Oct;191:51-80
pubmed: 27524653
mBio. 2020 Apr 14;11(2):
pubmed: 32291298
Virus Genes. 2020 Aug;56(4):480-497
pubmed: 32367411
Front Microbiol. 2021 Jan 15;11:615887
pubmed: 33519773
Sci Rep. 2019 Apr 12;9(1):5965
pubmed: 30979923
Antibiotics (Basel). 2020 Aug 15;9(8):
pubmed: 32824115
BMC Microbiol. 2011 Oct 11;11:226
pubmed: 21985151
FEMS Microbiol Lett. 2008 Jul;284(1):9-16
pubmed: 18462391
mBio. 2018 Jan 23;9(1):
pubmed: 29362234
Front Cell Infect Microbiol. 2017 Jun 30;7:290
pubmed: 28713777
Antimicrob Agents Chemother. 2013 Nov;57(11):5572-9
pubmed: 23979748
J Adv Res. 2019 Oct 12;21:169-176
pubmed: 32071785
Antibiotics (Basel). 2020 Mar 30;9(4):
pubmed: 32235599
Viruses. 2017 Mar 18;9(3):
pubmed: 28335451
FEMS Microbiol Lett. 2015 Jan;362(1):1-8
pubmed: 25790497
NPJ Biofilms Microbiomes. 2021 Apr 22;7(1):39
pubmed: 33888725
Clin Microbiol Rev. 2017 Nov 29;31(1):
pubmed: 29187396
Antibiotics (Basel). 2018 Mar 22;7(2):
pubmed: 29565804
PLoS One. 2017 Aug 10;12(8):e0182821
pubmed: 28797064
Antibiotics (Basel). 2020 Jan 16;9(1):
pubmed: 31963311
Nat Chem Biol. 2020 Jan;16(1):24-30
pubmed: 31686030
Antibiotics (Basel). 2021 Jun 16;10(6):
pubmed: 34208478
Front Microbiol. 2014 Oct 16;5:542
pubmed: 25360133