Characterization of the general stress response in Bartonella henselae

Abstract

Bacteria utilize a general stress response system to combat stresses from their surrounding environments. In alpha-proteobacteria, the general stress response uses an alternate sigma factor as the main regulator and incorporates it with a two-component system into a unique regulatory circuit. This system has been described in several alpha-proteobacterial species, including the pathogens Bartonella quintana and Brucella abortus. Most of the studies have focused on characterizing the PhyR anti-anti-sigma factor, the NepR anti-sigma factor, and the alternate sigma factor. However, not enough attention is directed toward studying the role of histidine kinases in the general stress response. Our study identifies the general stress response system in Bartonella henselae, where the gene synteny is conserved and both the PhyR and alternate sigma factor have similar sequence and domain structures with other alpha-proteobacteria. Our data showed that the general stress response genes are up-regulated under conditions that mimic the cat flea vector. Furthermore, we showed that both RpoE and PhyR positively regulate this system and that RpoE also affects transcription of genes encoding heme-binding proteins and the gene encoding the BadA adhesin. Finally, we identified a histidine kinase, annotated as BH13820 that can potentially phosphorylate PhyR.

Bartonella Species, an Emerging Cause of Blood-Culture-Negative Endocarditis

“…Likewise, the amount of surface-localized BadA is also highly variable, ranging from no detectable BadA in the Berlin-1 and ATCC 49793 strains to very high expression in the Marseille strain (72). Regulation of the badA gene has been attributed to the BatR/S two-component regulatory system (326) and the general stress response system (327). More recent studies have shown that a family of nine unannotated and highly transcribed RNAs designated Bartonella regulatory transcript (Brt1 to Brt9) found upstream of a putative transcriptional regulator protein are important in the regulation of badA (75).…”

MostSinorhizobium melilotiExtracytoplasmic Function Sigma Factors Control Accessory Functions

“…Our study is the first report of an alphaproteobacterial strain deleted for all of its multiple ECF σs. The number of ECF σs encoded in alphaproteobacterial genomes varies widely: obligate intracellular species with reduced genomes such as Rickettsia , Wolbachia , and Liberibacter lack ECF σs ( 66 ); bartonellae have only a single group ECF15 σ, which is involved in the GSR and host adaptation ( 67 , 68 ), and brucellae have two ECF σs—a group ECF16 σ and a group ECF15 σ involved in the GSR and mammalian infection ( 69 ). Model plant-associated rhizobia with expanded genomes, such as Sinorhizobium , Mesorhizobium , Rhizobium , and Bradyrhizobium possess up to 20 ECF σs ( 70 ).…”

Structure and function of HWE/HisKA2-family sensor histidine kinases

“…Staron and Mascher [34] noted that genomes containing PhyR and EcfG also contain HWE/HisKA2 kinases, and suggested this family of kinases as candidate regulators of GSR. Indeed, all histidine kinases demonstrated to phosphorylate PhyR and/or regulate GSR transcription to date are HWE/HisKA2 kinases [7,9–11,36–40]. The only histidine kinase known to signal to the GSR pathway that is not HWE/HisKA2 does so indirectly via an HWE/HisKA2 kinase that directly phosphorylates PhyR [9,41].…”