A functional menadione biosynthesis pathway is required for capsule production by Staphylococcus aureus

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dc.contributor.authorAltwiley, Dina
dc.contributor.authorBrignoli, Tarcisio
dc.contributor.authorEdwards, Andrew
dc.contributor.authorRecker, Mario
dc.contributor.authorLee, Jean C.
dc.contributor.authorMassey, Ruth C.
dc.date.accessioned2022-09-15T13:29:08Z
dc.date.available2022-09-15T13:29:08Z
dc.date.issued2021-11-26
dc.date.updated2022-09-15T13:22:36Z
dc.description.abstractStaphylococcus aureus is a major human pathogen that utilises a wide array of pathogenic and immune evasion strategies to cause disease. One immune evasion strategy, common to many bacterial pathogens, is the ability of S. aureus to produce a capsule that protects the bacteria from several aspects of the human immune system. To identify novel regulators of capsule production by S. aureus, we applied a genome wide association study (GWAS) to a collection of 300 bacteraemia isolates that represent the two major MRSA clones in UK and Irish hospitals: CC22 and CC30. One of the loci associated with capsule production, the menD gene, encodes an enzyme critical to the biosynthesis of menadione. Mutations in this gene that result in menadione auxotrophy induce the slow growing small-colony variant (SCV) form of S. aureus often associated with chronic infections due to their increased resistance to antibiotics and ability to survive inside phagocytes. Utilising such an SCV, we functionally verified this association between menD and capsule production. Although the clinical isolates with polymorphisms in the menD gene in our collections had no apparent growth defects, they were more resistant to gentamicin when compared to those with the wild-type menD gene. Our work suggests that menadione is involved in the production of the S. aureus capsule, and that amongst clinical isolates polymorphisms exist in the menD gene that confer the characteristic increased gentamicin resistance, but not the major growth defect associated with SCV phenotype.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid001108en
dc.identifier.citationAltwiley, D., Brignoli, T., Edwards, A., Recker, M., Lee, J. C. and Massey, R. C. (2021) 'A functional menadione biosynthesis pathway is required for capsule production by Staphylococcus aureus', Microbiology, 167(11), 001108 (11pp). doi: 10.1099/mic.0.001108en
dc.identifier.doi10.1099/mic.0.001108en
dc.identifier.eissn1465-2080
dc.identifier.endpage11en
dc.identifier.issn1350-0872
dc.identifier.issued11en
dc.identifier.journaltitleMicrobiologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/13609
dc.identifier.volume167en
dc.language.isoenen
dc.publisherMicrobiology Societyen
dc.rights© 2021, The Authors This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/en
dc.subjectCapsuleen
dc.subjectMenadioneen
dc.subjectPersistersen
dc.subjectSCVsen
dc.subjectSmall colony variantsen
dc.subjectStaphylococcus aureusen
dc.titleA functional menadione biosynthesis pathway is required for capsule production by Staphylococcus aureusen
dc.typeArticle (peer-reviewed)en
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