An Essential Regulatory System Originating from Polygenic Transcriptional Rewiring of PhoP-PhoQ of Xanthomonas campestris

Abstract

How essential, regulatory genes originate and evolve is intriguing because mutations of these genes not only lead to lethality in organisms, but also have pleiotropic effects since they control the expression of multiple downstream genes. Therefore, the evolution of essential, regulatory genes is not only determined by genetic variations of their own sequences, but also by the biological function of downstream genes and molecular mechanisms of regulation. To understand the origin of essential, regulatory genes, experimental dissection of the complete regulatory cascade is needed. Here, we provide genetic evidences to reveal that PhoP-PhoQ is an essential two-component signal transduction system in the gram-negative bacterium , but that its orthologs in other bacteria belonging to Proteobacteria are nonessential. Mutational, biochemical, and chromatin immunoprecipitation together with high-throughput sequencing analyses revealed that and of and its close relative are replaceable, and that the consensus binding motifs of the transcription factor PhoP are also highly conserved. PhoP in regulates the transcription of a number of essential, structural genes by directly binding to-regulatory elements (CREs); however, these CREs are lacking in the orthologous essential, structural genes in , and thus the regulatory relationships between PhoP and these downstream essential genes are disassociated. Our findings suggested that the recruitment of regulatory proteins by critical structural genes via transcription factor-CRE rewiring is a driving force in the origin and functional divergence of essential, regulatory genes.

Global Regulator PhoP is Necessary for Motility, Biofilm Formation, Exoenzyme Production, and Virulence of Xanthomonas citri Subsp. citri on Citrus Plants

“…oryzae , and X. campestris pv. campestris [18,20,22,23,38,39]. However, little is known about the PhoQ/PhoP proteins in the important plant pathogen X. citri subsp.…”

“…citri virulence, contributing to growth in planta , biofilm formation, LPS production, catalase activity, and resistance to environmental stress [6]. PhoQ/PhoP, which modulates adaptive responses to changes in levels of divalent cations, including magnesium, in the environment [16,17], is an evolutionarily active system involved in bacterial adaptation to various ecological niches [18]. In animal-pathogenic bacterium Salmonella enterica subsp.…”

“…campestris , PhoP controls the transcription of many essential, structural genes by directly binding to their cis -regulatory elements. However, it does not control the same essential genes in Pseudomonas aeruginosa , as no PhoP binding sites exist in the promoter regions of the genes [18]. A comparative analysis of the genomes of P. aeruginosa , X. campestris pv.…”

PhoPQ two-component regulatory system plays a global regulatory role in antibiotic susceptibility, physiology, stress adaptation, and virulence in Stenotrophomonas maltophilia

“…The unavailability of the phoQ mutant in this study was reminiscent of the essentiality of PhoPQ in Xanthomonas campestris [22]. With the exemption of Xanthomonas campestris, the reported phoQ orthologs in other bacteria, such as Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, and P. fluorescens, are mutable [8,23,24].…”

“…Peng et al have proposed the polygenic transcriptional rewiring model to explain the essentiality of PhoPQ in X. campestris. They suggested that the PhoP regulon of X. campestris includes several essential genes, but the PhoP regulons of other bacteria do not [22]. In contrast to PhoP essentiality in X. campestris, the phoP deletion mutant is viable in S. maltophilia.…”