Biotin-mediated growth and gene expression in Staphylococcus aureus is highly responsive to environmental biotin
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Biotin (Vitamin B7) is a critical enzyme co-factor in metabolic pathways important for bacterial survival. Biotin is obtained either from the environment or by de novo synthesis, with some bacteria capable of both. In certain species, the bifunctional protein BirA plays a key role in biotin homeostasis as it regulates expression of biotin biosynthetic enzymes in response to biotin demand and supply. Here, we compare the effect of biotin on the growth of two bacteria that possess a bifunctional BirA, namely Escherichia coli and Staphylococcus aureus. Unlike E. coli that could fulfill its biotin requirements through de novo synthesis, S. aureus showed improved growth rates in media supplemented with 10 nM biotin. S. aureus also accumulated more radiolabeled biotin from the media highlighting its ability to efficiently scavenge exogenous material. These data are consistent with S. aureus colonizing low biotin microhabitats. We also demonstrate that the S. aureus BirA protein is a transcriptional repressor of BioY, a subunit of the biotin transporter, and an operon containing yhfT and yhfS, the products of which have a putative role in fatty acid homeostasis. Increased expression of bioY is proposed to help cue S. aureus for efficient scavenging in low biotin environments.
KeywordsBiotin Gene expression/regulation Staphylococcus aureus BirA Biotin protein ligase
We thank the National BioResource Project (NIG, Japan) for the provision of bacterial strains.
J.S performed the experiments and data analysis and prepared the manuscript. B.A.E performed the data analysis. S.W.P. prepared the manuscript and data analysis. All authors contributed to the manuscript preparation and review.
This study was funded by the National Health and Medical Research Council of Australia Project Grant 1068885 awarded to SWP and GWB and Project Grants 1080784 and 1122582 awarded to CAM, and the Australian Research Council Discovery Project DP160101450 awarded to KES and DP150101856 and DP170102102 awarded to CAM. JS is a recipient of The University of Adelaide faculty divisional scholarship.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
This article does not contain any studies with human participants performed by any of the authors.
- Beckett D (2007) Biotin sensing: universal influence of biotin status on transcription. Annu Rev Genet 41:443–464. https://doi.org/10.1146/annurev.genet.41.042007.170450 CrossRefPubMedGoogle Scholar
- Cronan JE (2014b) Biotin and lipoic acid: synthesis, attachment and regulation. EcoSal Plus. https://doi.org/10.1128/ecosalplus.ESP-0001-2012.
- Finkenwirth F, Sippach M, Landmesser H, Kirsch F, Ogienko A, Grunzel M, Kiesler C, Steinhoff HJ, Schneider E, Eitinger T (2015) ATP-dependent conformational changes trigger substrate capture and release by an ECF-type biotin transporter. J Biol Chem 290(27):16929–16942. https://doi.org/10.1074/jbc.M115.654343 CrossRefPubMedPubMedCentralGoogle Scholar
- Henke SK, Cronan JE (2016) The Staphylococcus aureus group II biotin protein ligase BirA is an effective regulator of biotin operon transcription and requires the DNA binding domain for full enzymatic activity. Mol Microbiol 102(3):417–429. https://doi.org/10.1111/mmi.13470 CrossRefPubMedPubMedCentralGoogle Scholar
- Ringlstetter SL (2010) Identification of the biotin transporter in Escherichia coli, biotinylation of histones in Saccharomyces cerevisiae and analysis of biotin sensing in Saccharomyces cerevisiae. Doctoral thesis, Universität Regensburg, Germany. http://epub.uni-regensburg.de/15822/1/Diss_R_S.pdf
- Salaemae W, Booker GW, Polyak SW (2016) The role of biotin in bacterial physiology and virulence: a novel antibiotic target for Mycobacterium tuberculosis. Microbiol Spectrum 4(2):VMBF-0008-2015. https://doi.org/10.1128/microbiolspec.VMBF-0008-2015
- Soares da Costa TP, Yap MY, Perugini MA, Wallace JC, Abell AD, Wilce MCJ, Polyak SW, Booker GW (2014) Dual roles of F123 in protein homodimerization and inhibitor binding to biotin protein ligase from Staphylococcus aureus. Mol Microbiol 91(1):110–120. https://doi.org/10.1111/mmi.12446 CrossRefPubMedGoogle Scholar
- Weaver LH, Kwon K, Beckett D, Matthews BW (2001) Corepressor-induced organization and assembly of the biotin repressor: a model for allosteric activation of a transcriptional regulator. Proc Natl Acad Sci U S A 98(11):6045–6050. https://doi.org/10.1073/pnas.111128198 CrossRefPubMedPubMedCentralGoogle Scholar
- Woong Park S, Klotzsche M, Wilson DJ, Boshoff HI, Eoh H, Manjunatha U, Blumenthal A, Rhee K, Barry CE 3rd, Aldrich CC, Ehrt S, Schnappinger D (2011) Evaluating the sensitivity of Mycobacterium tuberculosis to biotin deprivation using regulated gene expression. PLoS Pathog 7(9):e1002264. https://doi.org/10.1371/journal.ppat.1002264 CrossRefPubMedPubMedCentralGoogle Scholar