The Lactobacillales (LB) stand apart among bacterial orders, using manganese (Mn) instead of iron to support their growth and swiftly ferment complex foods while acidifying their environment. The present work investigates whether a shift in the use of Mn could mark the origin of LB. Transmembrane carriers of the ubiquitous Slc11 family play key roles in LB physiology by catalyzing proton-dependent Mn import. In prior studies, the Slc11 clade found in LB (MntH Cb, MCb) showed both remarkable structural plasticity and highly efficient Mn uptake, and another Slc11 clade, MCg1, demonstrated divergent evolution coinciding with emergence of bacterial genera (e.g.,
Bordetella,
Achromobacter). Herein, the Slc11 clade MCb is subdivided in sister groups: MCb
ie and MCb
gut. MCb
ie derives directly from the Slc11 clade MCa, pointing an intermediate stage in the evolution of MCb
gut. MCb
ie predominates in marine Bacillaceae, is more conserved than MCb
gut, lacks the structural plasticity that typify MCb
gut carriers, and responds differently to identical mutagenesis. Exchanging MCb
ie/MCb
gut amino acid residues at sites that distinguish these clades showed conformation-dependent effects with both MCb
ie and MCb
gut templates, and the 3D location of the targeted sites in the carrier structure together suggests that the mechanism to open the inner gate, and release Mn into the cytoplasm, differs between MCb
ie and MCb
gut. Building on the established phylogeny for
Enterococcus revealed that a pair of genes encoding MCb
gut was present in the common ancestor of LB, as MCb
gu1 and MCb
gu2 templates exhibited distinct structural dynamics properties. These data are discussed when examining whether MCb
gut+ LB could emerge in the upper gut of early vertebrates (ca. 540 mya), through genome contraction and evolution toward Mn-centrism, as they specialized as gastric aids favoring stomach establishment in jawed vertebrates through bi-directional communication with host nervous, endocrine and immune systems.
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