QZ conceived the study, participated in experimental design and data analysis, and revised the manuscript. All authors have read and approved the final manuscript.”
“Background Two-component regulatory find more systems (TCRS) are the most abundant and widespread transcriptional regulators in bacteria, as indicated by the number of instances of the Pfam PF00072 response regulator receiver domain . Bacterial genomes typically contain dozens to hundreds of these systems . Response regulator domains of transcriptional regulatory proteins are phosphorylated by cognate sensor histidine kinase proteins in response to changes in environment or growth conditions . This phosphorylation
results in conformational change of the Eltanexor ic50 response regulator protein, leading to transcriptional activation or repression. Even with the recognized importance of these systems, very few of them have been characterized with regard to the signal input and the regulatory targets. The ExoS/ChvI two-component regulatory system, consisting of the membrane-spanning histidine protein kinase ExoS and the response Bafilomycin A1 clinical trial regulator ChvI, is found in
alphaproteobacterial genomes. In Agrobacterium tumefaciens, the ChvG/ChvI system is vital for plant tumor formation, and mutants are sensitive to acidic pH and detergents . The BvrS/BvrR system of Brucella abortus is required for virulence  and has a broad impact on cell envelope as well as carbon and nitrogen metabolism . The Bartonella henselae BatR/BatS system is also involved in regulating virulence-associated genes . Analysis of a mutant of the ExoS homolog of Rhizobium leguminosarum confirmed its requirement for successful nodule invasion and nitrogen fixation . This mutant also had a destabilized outer membrane, associated with reduction of ropB expression, as well as increased accumulation of intracellular poly-3-hydroxybutrate (PHB), and reduction in exopolysaccharide production. In all cases studied, ExoS/ChvI TCRS and its orthologs play a role, although not well understood, in the bacterial-host interaction. Sinorhizobium meliloti exoS was first identified through a Tn5 insertion mutant that resulted in
overproduction of exopolysaccharide due to disruption of the membrane-spanning portion of the protein, causing constitutive activation of the kinase activity, thus resulting in constant triclocarban phosphorylation of ChvI . Null mutants of exoS and chvI are able to trigger the formation of nodules, but those nodules do not develop normally and they do not fix nitrogen . The mutants do not grow on complex or in liquid media, and cultivation on defined agar-media is challenging, a condition that prompted an early conclusion that exoS and chvI are essential for S. meliloti viability . A chvI deletion mutant demonstrated enhanced motility, and reduction in PHB accumulation, the opposite of what was found for a R. leguminosarum exoS homolog mutant . Similar to the R.