Overcoming bacteriophage insensitivity in Staphylococcus aureus using clindamycin and azithromycinat sub-inhibitory concentrations

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dc.contributor.authorLiu, S.
dc.contributor.authorZhao, Y.
dc.contributor.authorHayes, A.
dc.contributor.authorHon, K.
dc.contributor.authorZhang, G.
dc.contributor.authorBennett, C.
dc.contributor.authorHu, H.
dc.contributor.authorFinnie, J.
dc.contributor.authorMorales, S.
dc.contributor.authorShearwin, L.
dc.contributor.authorPsaltis, A.J.
dc.contributor.authorShearwin, K.
dc.contributor.authorWormald, P.
dc.contributor.authorVreugde, S.
dc.date.issued2021
dc.description.abstractBackground: Staphylococcus aureus is a pathogen of major concern in both acute infections and chronic conditions such as chronic rhinosinusitis (CRS). Bacteriophage (phage) therapy has recently regained interest for its potential to treat infections caused by antibiotic resistant strains including Methicillin Resistant Staphylococcus aureus (MRSA). However, bacteria can adapt and become resistant to phages. The aim of this study is to determine the potential for antibiotics to overcome phage resistance. Methods: The susceptibility of S. aureus clinical isolates (CIs) to phages J-Sa36, Sa83 and Sa87 alone or in combination with protein synthesis inhibitor (PSI) antibiotics clindamycin, azithromycin and erythromycin was assessed using plaque spot assays, minimum inhibitory concentration (MIC) assays, double layer spot assays and resazurin assays. The safety and efficacy of subinhibitory PSI antibiotics in combination with phage was tested in a Sprague Dawley rat model of sinusitis infected with a phage resistant S. aureus CI. Results: All three antibiotics at subinhibitory concentrations showed synergy when combined with all 3 phages against S. aureus CIs in planktonic and biofilm form and could sensitize phage-resistant S. aureus to promote phage infection. The combination of topical subinhibitory clindamycin or azithromycin and phage was safe and could eradicate S. aureus sinonasal biofilms in vivo. Conclusion: Subinhibitory concentrations of PSI antibiotics could sensitize phage-resistant S. aureus and MRSA strains to phages in vitro and in vivo. This data supports the potential use of phage-PSI antibiotic combination therapies, in particular for difficult-to- treat infections with phage-resistant S. aureus and MRSA strains.
dc.description.statementofresponsibilitySha Liu, Yin Zhao, Andrew Hayes, Karen Hon, Guimin Zhang, Catherine Bennett, Hua Hu, John Finnie, Sandra Morales, Linda Shearwin, Alkis J. Psaltis, Keith Shearwin, Peter-John Wormald, Sarah Vreugde
dc.identifier.citationAllergy. European Journal of Allergy and Clinical Immunology, 2021; 76(11):3446-3458
dc.identifier.doi10.1111/all.14883
dc.identifier.issn0105-4538
dc.identifier.issn1398-9995
dc.identifier.orcidLiu, S. [0000-0003-2890-3247]
dc.identifier.orcidHayes, A. [0000-0001-8038-1656]
dc.identifier.orcidHon, K. [0000-0001-9836-6534]
dc.identifier.orcidFinnie, J. [0000-0003-2277-1693]
dc.identifier.orcidShearwin, L. [0000-0002-4504-6534]
dc.identifier.orcidPsaltis, A.J. [0000-0003-2197-0797] [0000-0003-2967-1855]
dc.identifier.orcidShearwin, K. [0000-0002-7736-2742]
dc.identifier.orcidWormald, P. [0000-0001-7753-7277]
dc.identifier.orcidVreugde, S. [0000-0003-4719-9785]
dc.identifier.urihttps://hdl.handle.net/2440/146101
dc.language.isoen
dc.publisherWiley
dc.rights© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
dc.source.urihttps://doi.org/10.1111/all.14883
dc.subjectbacteriophage therapy; chronic rhinosinusitis; clindamycin; S. aureus; subinhibitory
dc.subject.meshAnimals
dc.subject.meshRats
dc.subject.meshRats, Sprague-Dawley
dc.subject.meshStaphylococcus aureus
dc.subject.meshBacteriophages
dc.subject.meshStaphylococcal Infections
dc.subject.meshClindamycin
dc.subject.meshAnti-Bacterial Agents
dc.subject.meshMethicillin-Resistant Staphylococcus aureus
dc.titleOvercoming bacteriophage insensitivity in Staphylococcus aureus using clindamycin and azithromycinat sub-inhibitory concentrations
dc.typeJournal article
pubs.publication-statusPublished

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