Manganese uptake and streptococcal virulence
- 516 Downloads
Streptococcal solute-binding proteins (SBPs) associated with ATP-binding cassette transporters gained widespread attention first as ostensible adhesins, next as virulence determinants, and finally as metal ion transporters. In this mini-review, we will examine our current understanding of the cellular roles of these proteins, their contribution to metal ion homeostasis, and their crucial involvement in mediating streptococcal virulence. There are now more than 35 studies that have collected structural, biochemical and/or physiological data on the functions of SBPs across a broad range of bacteria. This offers a wealth of data to clarify the formerly puzzling and contentious findings regarding the metal specificity amongst this group of essential bacterial transporters. In particular we will focus on recent findings related to biological roles for manganese in streptococci. These advances will inform efforts aimed at exploiting the importance of manganese and manganese acquisition for the design of new approaches to combat serious streptococcal diseases.
KeywordsABC transporter Manganese Zinc Cluster A–I SBP Metal binding Solute-binding protein Streptococcus Virulence
This work was supported by the Australian Research Council Grant DP120103957 to C.A.M., the National Health & Medical Research Council Project Grant 1022240 and 1080784 to C.A.M., and National Institutes of Health Grants R01AI47841 and R56AI085195 to T.K. This work is solely the responsibility of the authors and does not reflect the views of the National Institutes of Health.
Conflict of interest
The authors declare no competing financial interests.
- Abate F, Malito E, Cozzi R, Lo Surdo P, Maione D, Bottomley MJ (2014) Apo, Zn2+-bound and Mn2+-bound structures reveal ligand binding properties of SitA from the pathogen Staphylococcus pseudintermedius. Biosci Rep 34:e00154Google Scholar
- Ammendola S, Pasquali P, Pistoia C, Petrucci P, Petrarca P, Rotilio G, Battistoni A (2007) High-affinity Zn2+ uptake system ZnuABC is required for bacterial zinc homeostasis in intracellular environments and contributes to the virulence of Salmonella enterica. Infect Immun 75:5867–5876PubMedCentralPubMedGoogle Scholar
- Daly MJ (2009) A new perspective on radiation resistance based on Deinococcus radiodurans. Nat Rev Micro 7:237–245Google Scholar
- Froeliger EH, Fives-Taylor P (2000) Streptococcus parasanguis FimA does not contribute to adherence to SHA (abstract 1552). J Dent Res 79:337Google Scholar
- Linke C, Caradoc-Davies TT, Proft T, Baker EN (2008) Purification, crystallization and preliminary crystallographic analysis of Streptococcus pyogenes laminin-binding protein Lbp. Acta Crystallogr Sect F 64:141–143Google Scholar
- Locher KP (2009) Review. Structure and mechanism of ATP-binding cassette transporters. Philos Trans R Soc Lond B 364:239–245Google Scholar
- Oetjen J, Fives-Taylor P, Froeliger EH (2002) The divergently transcribed Streptococcus parasanguis virulence-associated fimA operon encoding an Mn(2+)-responsive metal transporter and pepO encoding a zinc metallopeptidase are not coordinately regulated. Infect Immun 70:5706–5714PubMedCentralPubMedGoogle Scholar
- Ragunathan P, Spellerberg B, Ponnuraj K (2009a) Expression, purification, crystallization and preliminary crystallographic analysis of laminin-binding protein (Lmb) from Streptococcus agalactiae. Acta Crystallogr Sect F 65:492–494Google Scholar
- Rantanen MK, Lehtiö L, Rajagopal L, Rubens CE, Goldman A (2007) Structure of the Streptococcus agalactiae family II inorganic pyrophosphatase at 2.80 Å resolution. Acta Crystallogr Sect D 63:738–743Google Scholar
- Smith AJ, Ward PN, Field TR, Jones CL, Lincoln RA, Leigh JA (2003) MtuA, a lipoprotein receptor antigen from Streptococcus uberis, is responsible for acquisition of manganese during growth in milk and is essential for infection of the lactating bovine mammary gland. Infect Immun 71:4842–4849PubMedCentralPubMedGoogle Scholar