Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilms
Abstract Staphylococcus aureus is considered a priority pathogen due to its increasing acquisition of antibiotic resistance determinants. Additionally, this microbe has the ability to form recalcitrant biofilms on different biotic and inert surfaces. In this context, bacteriophages and their derived...
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doaj-0e64b4831f964b449d236678ed4559972021-04-25T11:47:49ZengNature Publishing Groupnpj Biofilms and Microbiomes2055-50082021-04-017111010.1038/s41522-021-00208-5Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilmsAna Catarina Duarte0Lucía Fernández1Vincent De Maesschalck2Diana Gutiérrez3Ana Belén Campelo4Yves Briers5Rob Lavigne6Ana Rodríguez7Pilar García8Instituto de Productos Lácteos de Asturias (IPLA-CSIC)Instituto de Productos Lácteos de Asturias (IPLA-CSIC)Laboratory of Applied Biotechnology, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent UniversityLaboratory of Applied Biotechnology, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent UniversityInstituto de Productos Lácteos de Asturias (IPLA-CSIC)Laboratory of Applied Biotechnology, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent UniversityLaboratory of Gene Technology, Department of Biosystems, Faculty of Bioscience Engineering KU LeuvenInstituto de Productos Lácteos de Asturias (IPLA-CSIC)Instituto de Productos Lácteos de Asturias (IPLA-CSIC)Abstract Staphylococcus aureus is considered a priority pathogen due to its increasing acquisition of antibiotic resistance determinants. Additionally, this microbe has the ability to form recalcitrant biofilms on different biotic and inert surfaces. In this context, bacteriophages and their derived lytic proteins may be a forward-looking strategy to help combat staphylococcal biofilms. However, these antimicrobials exhibit individual limitations that may be overcome by combining them with other compounds. This work investigates the combination of a phage-derived lytic protein, CHAPSH3b, and the virulent bacteriophage phiIPLA-RODI. The obtained results show the synergy between both antimicrobials for the treatment of 24-h-old S. aureus biofilms, with greater reductions in viable cell counts observed when phage and lysin are applied together compared to the individual treatments. Time-kill curves and confocal microscopy revealed that the fast antibacterial action of CHAPSH3b reduces the population up to 7 hours after initial exposure, which is subsequently followed by phage predation, limiting regrowth of the bacterial population. Moreover, at least 90% of bacteriophage insensitive mutants are susceptible to the lytic protein. Therefore, CHAPSH3b might help curtail the development of phage resistance during treatment. The combination of the lysin and phiIPLA-RODI also showed promising results in an ex vivo pig skin model of wound infection. Overall, the results of this study demonstrate that the combination of phage-derived lytic proteins and bacteriophages can be a viable strategy to develop improved antibiofilm products.https://doi.org/10.1038/s41522-021-00208-5 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ana Catarina Duarte Lucía Fernández Vincent De Maesschalck Diana Gutiérrez Ana Belén Campelo Yves Briers Rob Lavigne Ana Rodríguez Pilar García |
spellingShingle |
Ana Catarina Duarte Lucía Fernández Vincent De Maesschalck Diana Gutiérrez Ana Belén Campelo Yves Briers Rob Lavigne Ana Rodríguez Pilar García Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilms npj Biofilms and Microbiomes |
author_facet |
Ana Catarina Duarte Lucía Fernández Vincent De Maesschalck Diana Gutiérrez Ana Belén Campelo Yves Briers Rob Lavigne Ana Rodríguez Pilar García |
author_sort |
Ana Catarina Duarte |
title |
Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilms |
title_short |
Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilms |
title_full |
Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilms |
title_fullStr |
Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilms |
title_full_unstemmed |
Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilms |
title_sort |
synergistic action of phage phiipla-rodi and lytic protein chapsh3b: a combination strategy to target staphylococcus aureus biofilms |
publisher |
Nature Publishing Group |
series |
npj Biofilms and Microbiomes |
issn |
2055-5008 |
publishDate |
2021-04-01 |
description |
Abstract Staphylococcus aureus is considered a priority pathogen due to its increasing acquisition of antibiotic resistance determinants. Additionally, this microbe has the ability to form recalcitrant biofilms on different biotic and inert surfaces. In this context, bacteriophages and their derived lytic proteins may be a forward-looking strategy to help combat staphylococcal biofilms. However, these antimicrobials exhibit individual limitations that may be overcome by combining them with other compounds. This work investigates the combination of a phage-derived lytic protein, CHAPSH3b, and the virulent bacteriophage phiIPLA-RODI. The obtained results show the synergy between both antimicrobials for the treatment of 24-h-old S. aureus biofilms, with greater reductions in viable cell counts observed when phage and lysin are applied together compared to the individual treatments. Time-kill curves and confocal microscopy revealed that the fast antibacterial action of CHAPSH3b reduces the population up to 7 hours after initial exposure, which is subsequently followed by phage predation, limiting regrowth of the bacterial population. Moreover, at least 90% of bacteriophage insensitive mutants are susceptible to the lytic protein. Therefore, CHAPSH3b might help curtail the development of phage resistance during treatment. The combination of the lysin and phiIPLA-RODI also showed promising results in an ex vivo pig skin model of wound infection. Overall, the results of this study demonstrate that the combination of phage-derived lytic proteins and bacteriophages can be a viable strategy to develop improved antibiofilm products. |
url |
https://doi.org/10.1038/s41522-021-00208-5 |
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