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Tytuł:
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Development of Advanced Chimeric Endolysin to Control Multidrug-Resistant Staphylococcus aureus through Domain Shuffling.
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Autorzy:
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Lee C; Department of Food and Animal Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.; Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Kim J; Department of Food and Animal Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.; Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Son B; Department of Food and Animal Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Ryu S; Department of Food and Animal Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.; Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.; Center for Food and Bioconvergence, Seoul National University, Seoul 08826, Republic of Korea.
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Źródło:
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ACS infectious diseases [ACS Infect Dis] 2021 Aug 13; Vol. 7 (8), pp. 2081-2092. Date of Electronic Publication: 2021 May 28.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Washington, DC : ACS Publications, [2015]-
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MeSH Terms:
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Methicillin-Resistant Staphylococcus aureus*
Staphylococcal Infections*/drug therapy
Animals ; Endopeptidases/genetics ; Mice ; Staphylococcus aureus
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Contributed Indexing:
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Keywords: MRSA; Staphylococcus aureus; antibiotic alternative; chimeric endolysin; therapeutic agent
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Substance Nomenclature:
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EC 3.4.- (Endopeptidases)
EC 3.4.99.- (endolysin)
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Entry Date(s):
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Date Created: 20210528 Date Completed: 20210909 Latest Revision: 20210909
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Update Code:
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20240105
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DOI:
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10.1021/acsinfecdis.0c00812
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PMID:
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34047546
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The increase in the prevalence of multidrug-resistant (MDR) Staphylococcus aureus with strong biofilm-forming capacity poses a serious public health concern. Endolysins derived from bacteriophages are a promising solution for antibiotic resistance problems. However, some natural staphylococcal endolysins have several shortcomings, such as low solubility and high sequence homology among domains. To overcome these limitations, we constructed a hybrid endolysin library by swapping an enzymatically active domain (EAD) and a cell wall binding domain (CBD) of 12 natural staphylococcal endolysins. We found a novel chimeric endolysin, ClyC, which showed enhanced lytic activity against S. aureus compared to its parental endolysin forms. ClyC also exhibited strong antibacterial activity against S. aureus in various biomatrices, such as milk and blood. Moreover, the treatment of chimeric endolysin effectively eradicated biofilms of multidrug-resistant bacteria, including methicillin-resistant S. aureus (MRSA), S. epidermidis (MRSE), and S. aureus clinical isolates. In an in vivo mouse infection model, ClyC showed effective protection capability against methicillin-resistant Staphylococcus aureus (MRSA) without any toxic effects. Taken together, our data suggest that the chimeric endolysin ClyC can be considered a potential antibacterial agent against multidrug-resistant S. aureus and may have clinical relevance.
