| The major source of variation generating phenotypic diversity in prokaryotes is thought to result from the gain and loss of genes. However, the differential regulation of homologous genes may also have important implications for the ecology and evolution of bacterial species.; Inducible membrane remodeling is an adaptive mechanism that enables gram-negative bacteria to resist killing by toxic compounds, such as the cationic antimicrobial peptide polymyxin B. In Salmonella enterica, modification of the lipopolysaccharide (LPS) is governed by the PmrA/PmrB two-component regulatory system, which is activated directly by exposure to Fe3+ , and in low Mg2+, in a process dependent on the PhoP/PhoQ two-component system and the PhoP-regulated PmrD protein, a posttranslational activator of the PmrA protein.; Escherichia coli, the close relative of Salmonella , harbors the genetic components required to mediate polymyxin B resistance; however, it is unable to modify its LPS during growth in low Mg 2+. We demonstrate that this disparity in inducible membrane remodeling results from the differential regulation of homologous genes and not from differences in gene content. We establish that the PmrD protein is responsible for this phenotype and that selection might have driven the molecular and functional divergence between the PmrD proteins of the two genera.; Examination of the transcriptional activation of inducible membrane remodeling among enteric species revealed that different bacterial species have adopted distinct regulatory solutions to express the biosynthesis genes required for polymyxin B resistance during growth in low Mg2+ environments. Moreover, we propose a likely scenario for the evolutionary history of this property.; These results demonstrate that the differential regulation of conserved genes can mediate phenotypic traits that distinguish closely related bacterial species. This can be due to allelic variation in orthologous regulatory proteins, such as PmrD, or the result of differences in cis regulatory sequences. |
