Figure 1. Manganese homeostasis proteins across bacteria and their regulation by Mn.

The complement of common Mn importer and exporter families in bacteria and their typical regulation by a transcription factor or a riboswitch. (a) Two major classes of Mn importers (green) are the NRAMP family, exemplified by MntH, and ABC transporters, the Mn-specific versions of which have various names in different species, commonly SitABCD in gram-negative bacteria and MntABC in gram-positive bacteria. Four major classes of exporters (blue) used to efflux Mn are the CDF, MntP, UPF0016, and P-type ATPase families, with specific protein examples as indicated. The TerC family proteins (blue-green) may function as a Mn importer or exporter depending on the organism [27,32]. Other rare Mn transporters are not shown, including the importers MntX (ArsP_2 type), MntA (P-type ATPase), and the exporter CtpC (P-type ATPase) [54–56]. The typical mechanism of regulation is indicated by a 1 or 2 below the protein names. (b) Two main mechanisms are employed to regulate gene expression of Mn transporters: (1) transcriptional regulation via MntR (or sometimes Mur [57], not shown) or (2) post-transcriptional regulation via the yybP-ykoY riboswitch. A + sign indicates upregulation, and a − sign indicates downregulation. Other metal homeostasis proteins impacted by these regulators are not shown, but often include Fe importers upregulated in various bacteria by MntR and several families of proteins of unknown function induced by the riboswitch. (c) Once inside cells, Mn (purple) is partitioned into different intracellular pools, including Mn bound to proteins, DNA and RNA, small molecule chelates (crescent), and possibly some fully hydrated ions. The total Mn quota consists of Mn ions that are weakly bound and exchangeable, as well as kinetically trapped Mn (e.g., buried in proteins such as Mn-SOD or MncA [2,52]).