Manganese uptake and streptococcal virulence

Abstract

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.

Figure 1. Phylogeny of the cluster A-I SBPs of known function

The sequences of the 38 SBPs included in this study were obtained from the NCBI and had the following GI numbers: AdcA_Spn, GI:116516060 (Bayle et al. 2011); AdcAII_Spn, GI:116515739 (Bayle et al. 2011; Loisel et al. 2008); FimA_Spa, GI:504525723 (Oetjen et al. 2002); Lbp_Spy, GI:16151821 (Linke et al. 2008; Linke et al. 2009); Lmb_Sag, GI:22537388 (Ragunathan et al. 2009a; Ragunathan et al. 2009b); MntA_Ban, GI:229264967 (Gat et al. 2005); MtsA_Sag, GI:22537676 (Bray et al. 2009); MtsA_Spy, GI:383493478 (Sun et al. 2009; Sun et al. 2008); MntC_Ngo, GI:59800624 (Lim et al. 2008); MntC_Sau, GI:88194402 (Horsburgh et al. 2002a); MntC_Syn, GI:1653002 (Adir et al. 2002); MtsA_Sin, GI:343481042 (Zou et al. 2010); MtuA_Sub, GI:222113460 (Banerjee et al. 2003); PsaA_Spn, GI:116515973 (McDevitt et al. 2011); ScaA_Sgo, GI:310633 (Jakubovics et al. 2000; Kolenbrander et al. 1998); SitA_Eco, GI:84060846 (Sabri et al. 2006); SitA_Sen, GI:16761638 (Zhou et al. 1999); SitA_Sme, GI:15966779 (Chao et al. 2004; Davies and Walker 2007; Platero et al. 2004); SitA_Sps, GI:10135086 (Abate et al. 2014); SitC_Sep, GI:57636840 (Cockayne et al. 1998; Massonet et al. 2006); SloC_Smu, GI:8925939 (Paik et al. 2003); SsaB_San, GI:153826 (Crump et al. 2014); TroA_Ssu, GI:386583456 (Wichgers Schreur et al. 2011; Zheng et al. 2011); TroA_Tpa, GI:1777933 (Deka et al. 1999; Desrosiers et al. 2007; Lee et al. 1999; Lee et al. 2002); YfeA_Ype, GI:1245464 (Bearden and Perry 1999; Bearden et al. 1998); ZnuA_Cje, GI:384442496 (Davis et al. 2009); ZnuA_Eco, GI:298380994 (Patzer and Hantke 1998); ZnuA_Hin, GI:16272089 (Lu et al. 1997); ZnuA_Sen, GI:161353595 (Ammendola et al. 2007; Ilari et al. 2011); ZnuA_Syn, GI:38492833 (Banerjee et al. 2003); ZnuA_Tpa, GI:378974662 (Desrosiers et al. 2007); ZnuA_Vpa, GI:28901162 (Gribenko et al. 2013); ZnuA_Ype, GI:22126135 (Bobrov et al. 2014); ZnuA_Yru, GI:238754865 (Dahiya and Stevenson 2010); YcdH_Bsu, GI:2415736 (Gaballa and Helmann 1998; Gaballa et al. 2002). The three-letter abbreviation for bacterial species used was: Ban, Bacillus anthrasis; Cje, Campylobacter jejuni; Eco, Escherichia coli; Hin, Haemophilus influenzae; Ngo, Neisseria gonorrhoeae; Nme, Neisseria meningitidis; Sag, Streptococcus agalactiae; San, Streptococcus sanguinis; Sau, Staphylococcus aureus; Sen, Salmonella enterica; Sep, Staphylococcus epidermidis; Sgo, Streptococcus gordonii; Sin, Streptococcus iniae; Sme, Sinorhizobium meliloti; Smu, Streptococcus mutans; Spa, Streptococcus parasanguinis; Spn, Streptococcus pneumoniae; Sps, Staphylococcus pseudintermedius; Spy, Streptococcus pyogenes; Ssu, Streptococcus suis; Sub, Streptococcus uberis; Syn, Synechocystis; Tpa, Treponema pallidum; Vpa, Vibrio parahaemolyticus; Ype, Yersinia pestis; Yru, Yersinia ruckeri.