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Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b : a combination strategy to target Staphylococcus aureus biofilms

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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.
Keywords
BACTERIOPHAGE ENDOLYSINS, BACTERIAL BIOFILMS, GENE-EXPRESSION, RESISTANCE, MASTITIS, REMOVAL, ENZYMES, BAP

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MLA
Duarte, Ana Catarina, et al. “Synergistic Action of Phage PhiIPLA-RODI and Lytic Protein CHAPSH3b : A Combination Strategy to Target Staphylococcus Aureus Biofilms.” NPJ BIOFILMS AND MICROBIOMES, vol. 7, no. 1, 2021, doi:10.1038/s41522-021-00208-5.
APA
Duarte, A. C., Fernández, L., De Maesschalck, V., Gutierrez Fernandez, D., Campelo, A. B., Briers, Y., … García, P. (2021). Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b : a combination strategy to target Staphylococcus aureus biofilms. NPJ BIOFILMS AND MICROBIOMES, 7(1). https://doi.org/10.1038/s41522-021-00208-5
Chicago author-date
Duarte, Ana Catarina, Lucía Fernández, Vincent De Maesschalck, Diana Gutierrez Fernandez, Ana Belén Campelo, Yves Briers, Rob Lavigne, Ana Rodríguez, and Pilar García. 2021. “Synergistic Action of Phage PhiIPLA-RODI and Lytic Protein CHAPSH3b : A Combination Strategy to Target Staphylococcus Aureus Biofilms.” NPJ BIOFILMS AND MICROBIOMES 7 (1). https://doi.org/10.1038/s41522-021-00208-5.
Chicago author-date (all authors)
Duarte, Ana Catarina, Lucía Fernández, Vincent De Maesschalck, Diana Gutierrez Fernandez, Ana Belén Campelo, Yves Briers, Rob Lavigne, Ana Rodríguez, and Pilar García. 2021. “Synergistic Action of Phage PhiIPLA-RODI and Lytic Protein CHAPSH3b : A Combination Strategy to Target Staphylococcus Aureus Biofilms.” NPJ BIOFILMS AND MICROBIOMES 7 (1). doi:10.1038/s41522-021-00208-5.
Vancouver
1.
Duarte AC, Fernández L, De Maesschalck V, Gutierrez Fernandez D, Campelo AB, Briers Y, et al. Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b : a combination strategy to target Staphylococcus aureus biofilms. NPJ BIOFILMS AND MICROBIOMES. 2021;7(1).
IEEE
[1]
A. C. Duarte et al., “Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b : a combination strategy to target Staphylococcus aureus biofilms,” NPJ BIOFILMS AND MICROBIOMES, vol. 7, no. 1, 2021.
@article{8705537,
  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.}},
  articleno    = {{39}},
  author       = {{Duarte, Ana Catarina and Fernández, Lucía and De Maesschalck, Vincent and Gutierrez Fernandez, Diana and Campelo, Ana Belén and Briers, Yves and Lavigne, Rob and Rodríguez, Ana and García, Pilar}},
  issn         = {{2055-5008}},
  journal      = {{NPJ BIOFILMS AND MICROBIOMES}},
  keywords     = {{BACTERIOPHAGE ENDOLYSINS,BACTERIAL BIOFILMS,GENE-EXPRESSION,RESISTANCE,MASTITIS,REMOVAL,ENZYMES,BAP}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{10}},
  title        = {{Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b : a combination strategy to target Staphylococcus aureus biofilms}},
  url          = {{http://dx.doi.org/10.1038/s41522-021-00208-5}},
  volume       = {{7}},
  year         = {{2021}},
}

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