Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Richmond, Virginia, USA.
Mol Microbiol. 2022 Feb;117(2):353-374. doi: 10.1111/mmi.14853. Epub 2021 Dec 18.
Streptococcus sanguinis is an important cause of infective endocarditis. In strain SK36, the ABC-family manganese transporter, SsaACB, is essential for virulence. We have now identified a ZIP-family protein, TmpA, as a secondary manganese transporter. A tmpA mutant had no phenotype, but a ΔssaACB ΔtmpA mutant was more attenuated for serum growth and for virulence in a rabbit model than its ΔssaACB parent. The growth of both mutants was restored by supplemental manganese, but the ΔssaACB ΔtmpA mutant required twenty-fold more and accumulated less. Although ZIP-family proteins are known for zinc and iron transport, TmpA-mediated transport of either metal was minimal. While ssaACB appears ubiquitous in St. sanguinis, tmpA was present in a majority of strains and a mntH gene encoding an NRAMP-family transporter was identified in relatively few, including VMC66. As in SK36, deletion of ssaACB greatly diminished VMC66 endocarditis virulence and serum growth, and deletion of tmpA from this mutant diminished virulence further. Virulence was not significantly altered by deletion of mntH from either VMC66 or its ΔssaACB mutant. This and the accompanying paper together suggest that SsaACB is of primary importance for endocarditis virulence while secondary transporters TmpA and MntH contribute to growth under differing conditions.
血链球菌是感染性心内膜炎的重要病因。在 SK36 菌株中，ABC 家族锰转运体 SsaACB 对毒力至关重要。我们现在已经确定了一种 ZIP 家族蛋白TmpA 是次要锰转运体。TmpA 突变体没有表型，但与 ΔssaACB 亲本相比，ΔssaACB ΔtmpA 突变体在血清生长和兔模型中的毒力方面更为衰减。两种突变体的生长都可以通过补充锰来恢复，但 ΔssaACB ΔtmpA 突变体需要多 20 倍的锰，并且积累的锰更少。尽管 ZIP 家族蛋白以转运锌和铁而闻名，但 TmpA 介导的这两种金属的转运作用都很微小。虽然 ssaACB 似乎在血链球菌中普遍存在，但 tmpA 存在于大多数菌株中，并且在相对较少的菌株中鉴定出编码 NRAMP 家族转运体的 mntH 基因，包括 VMC66。与 SK36 一样，ssaACB 的缺失大大降低了 VMC66 的心内膜炎毒力和血清生长，而从该突变体中缺失 tmpA 则进一步降低了毒力。从 VMC66 或其 ΔssaACB 突变体中缺失 mntH 并没有显著改变毒力。这篇论文和附带的论文一起表明，SsaACB 对心内膜炎毒力至关重要，而次要转运体 TmpA 和 MntH 在不同条件下有助于生长。
