Transcription factor function and promoter architecture govern the evolution of bacterial regulons

Abstract

Evolutionary changes in ancestral regulatory circuits can bring about phenotypic differences between related organisms. Studies of regulatory circuits in eukaryotes suggest that these modifications result primarily from changes in cis-regulatory elements (as opposed to alterations in the transcription factors that act upon these sequences). It is presently unclear how the evolution of gene regulatory circuits has proceeded in bacteria, given the rampant effects of horizontal gene transfer, which has significantly altered the composition of bacterial regulons. We now demonstrate that the evolution of the regulons governed by the regulatory protein PhoP in the related human pathogens Salmonella enterica and Yersinia pestis has entailed functional changes in the PhoP protein as well as in the architecture of PhoP-dependent promoters. These changes have resulted in orthologous PhoP proteins that differ both in their ability to promote transcription and in their role as virulence regulators. We posit that these changes allow bacterial transcription factors to incorporate newly acquired genes into ancestral regulatory circuits and yet retain control of the core members of a regulon.cis-regulatory elements ͉ horizontal gene transfer ͉ PhoP ͉ Salmonella ͉ Yersinia

Autoregulation of PhoP/PhoQ and Positive Regulation of the Cyclic AMP Receptor Protein-Cyclic AMP Complex by PhoP in Yersinia pestis

“…PhoP not only directly regulates the expression of specific genes, including virulence-related ones, but also controls various indirect targets by acting on a set of regulators in Y. pestis (5,15,16). PhoP recognizes the promoter region of rovA to repress its transcription in Y. pestis (19).…”

“…CRP senses the switch of catabolites, and glucose may be the only free sugar that the bacteria can detect in hosts, whereas the presence of glucose stops the CRPcAMP machinery (10). Both PhoP and CRP are global regulators controlling complex cellular pathways, including multiple virulence determinants in Y. pestis (5,(11)(12)(13)(14)(15)(16).…”

Mechanisms and Evolution of Control Logic in Prokaryotic Transcriptional Regulation

“…In another study, B. subtilis ComK, which is normally a transcriptional activator, appeared to function mainly as a repressor when it was heterologously expressed in L. lactis (286). Also, by studying PhoP orthologues from Salmonella enterica and Yersinia pestis (79% identical), Perez and Groisman found that they acted differently on promoters (one able and one unable to induce transcription) in the two species even in a case where both orthologues bound the PhoP binding site in the promoter effectively (230). Apparently, the evolution of TF-TFBS interactions involves a complex interplay of both minor modifications to the sequences of TFs and functional changes in the architecture of promoters.…”

Yersinia pestisTwo-Component Gene Regulatory Systems Promote Survival in Human Neutrophils

“…In both S. enterica serovar Typhimurium and Y. pestis, this property is conferred in part through covalent modification of lipid A phosphate residues with 4-aminoarabinose. Although important divergent regulatory mechanisms exist between genera, 4-aminoarabinose metabolism is controlled by enzymes encoded by ugd and within the pbgP operon (including pmrK) (38). PhoP is a global regulator of gene expression that governs a diversity of transcripts in Y. pestis, including those required for 4-aminoarabinose biosynthesis (15,41,54,56).…”