@article{Altwiley:2021:10.1101/2021.06.02.446699,
author = {Altwiley, D and Brignoli, T and Edwards, A and Recker, M and Lee, J and Massey, RC},
doi = {10.1101/2021.06.02.446699},
title = {A Functional Menadione Biosynthesis Pathway is Required for Capsule Production by <i>Staphylococcus aureus</i>},
url = {http://dx.doi.org/10.1101/2021.06.02.446699},
year = {2021}
}

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TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p><jats:italic>Staphylococcus aureus</jats:italic> 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 <jats:italic>S. aureus</jats:italic> to produce a capsule that protects the bacteria from several aspects of the human immune system. To identify novel regulators of capsule production by <jats:italic>S. aureus</jats:italic> 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 <jats:italic>menD</jats:italic> 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 <jats:italic>S. aureus</jats:italic> 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 <jats:italic>menD</jats:italic> and capsule production. Although the clinical isolates with polymorphisms in the <jats:italic>menD</jats:italic> gene in our collections had no apparent growth defects, they were more resistant to gentamicin when compared to those with the wild-type <jats:italic>menD</jats:italic> gene. Our work suggests that menadione plays a critical role in the production of the <jats:italic>S. aureus</jats:italic> capsule, and that amongst clinical isolates polymorphisms exist in the <jats:italic>menD</jats:italic> gene that confer the characteristic increased gentamicin resistance, but not the major growth defect associated with S
AU  - Altwiley,D
AU  - Brignoli,T
AU  - Edwards,A
AU  - Recker,M
AU  - Lee,J
AU  - Massey,RC
DO  - 10.1101/2021.06.02.446699
PY  - 2021///
TI  - A Functional Menadione Biosynthesis Pathway is Required for Capsule Production by <i>Staphylococcus aureus</i>
UR  - http://dx.doi.org/10.1101/2021.06.02.446699
ER  - 

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