PhoB Regulates the Survival of Bacteroides fragilis in Peritoneal Abscesses

Wakimoto, Shin; Nakayama‐Imaohji, Haruyuki; Ichimura, Minoru; Hirakawa, Hideki; Hayashi, Tetsuya; Yasutomo, Koji; Kuwahara, Tomomi

doi:10.1371/journal.pone.0053829

Cited by 14 publications

(13 citation statements)

References 37 publications

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“…This observation indicates that inappropriate Pho activation is detrimental to bacterial pathogenesis. Other studies demonstrate that disruption of PhoPR can also be detrimental to bacterial virulence (12,(22)(23)(24)(25), including our observation that PhoPR is necessary for wild-type levels of staphylococcal pathogenesis. Notably, in this work, we observe that ΔphoPR and ΔpstSCAB ΔnptA mutants are similarly attenuated in the liver.…”

Section: Discussionsupporting

confidence: 64%

“…PhoPR is important for virulence of S. aureus independent of P i transporter regulation. In several bacterial pathogens, PhoPR has a critical role in virulence (12,(22)(23)(24)(25). Additionally, phosphate metabolism has been linked to antibiotic resistance (46); specifically, a point mutation in pitA increases stationary-phase tolerance of S. aureus to the clinically important antibiotic daptomycin (DAP) (47).…”

Section: Resultsmentioning

confidence: 99%

“…To regulate P i acquisition and homeostasis, many bacteria contain a P i -responsive two-component system (TCS) called PhoPR (PhoBR in Escherichia coli and other Gramnegative organisms, PnpRS in Streptococcus pneumoniae, and SenX3-RegX3 in M. tuberculosis) (21). The importance of maintaining proper P i homeostasis is highlighted by the observation that deletion or disruption of PhoPR decreases the virulence of E. coli, V. cholerae, M. tuberculosis, and others (12,(22)(23)(24)(25). In these organisms, PhoPR is FIG 1 Model of phosphate uptake and homeostasis in S. aureus.…”

mentioning

confidence: 99%

“…activated upon P i starvation and induces the transcription of genes involved in highaffinity phosphate assimilation, collectively called the Pho regulon. The Pho regulon of a variety of organisms (Caulobacter crescentus, Bacillus subtilis, and Streptomyces coelicolor), including human pathogens (pathogenic E. coli, Salmonella enterica serovar Typhimurium, S. pneumoniae, and Bacteroides fragilis), has been elucidated (20,23,(26)(27)(28)(29)(30). Conserved, direct targets of PhoPR frequently include PstSCAB, an alkaline phosphatase, and transporters for organic sources of phosphate, such as glycerol-3phosphate (21,31).…”

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confidence: 99%

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PhoPR Contributes to Staphylococcus aureus Growth during Phosphate Starvation and Pathogenesis in an Environment-Specific Manner

2018

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Microbial pathogens must obtain all essential nutrients, including phosphate, from the host. To optimize phosphate acquisition in diverse and dynamic environments, such as mammalian tissues, many bacteria use the PhoPR two-component system. Despite the necessity of this system for virulence in several species, PhoPR has not been studied in the major human pathogen To illuminate its role in staphylococcal physiology, we initially assessed whether PhoPR controls the expression of the three inorganic phosphate (P) importers (PstSCAB, NptA, and PitA) in This analysis revealed that PhoPR is required for the expression of and and can modulate expression. Consistent with a role in phosphate homeostasis, PhoPR-mediated regulation of the transporters is influenced by phosphate availability. Further investigations revealed that PhoPR is necessary for growth under P-limiting conditions, and in some environments, its primary role is to induce the expression of or Interestingly, in other environments, PhoPR is necessary for growth independent of P transporter expression, indicating that additional PhoPR-regulated factors promote adaptation to low-P conditions. Together, these data suggest that PhoPR differentially contributes to growth in an environment-specific manner. In a systemic infection model, a mutant of lacking PhoPR is highly attenuated. Further investigation revealed that PhoPR-regulated factors, in addition to P transporters, are critical for staphylococcal pathogenesis. Cumulatively, these findings point to an important role for PhoPR in orchestrating P acquisition as well as transporter-independent mechanisms that contribute to virulence.

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Section: Discussionsupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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PhoPR Contributes to Staphylococcus aureus Growth during Phosphate Starvation and Pathogenesis in an Environment-Specific Manner

2018

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“…86 Under these Pi-limiting conditions, it has been shown that in Bacteroides fragilis PhoB was necessary for successful infection and survival in peritoneal abscesses. 87 In this study, activation of the Pho regulon induced a shift of B. fragilis from gut symbiosis to pathogenicity. Recently, it has been shown that Mycobacterium tuberculosis requires the Pst system to negatively regulate activity of RegX3 (a PhoB analog) in response to in vivo available Pi.…”

Section: Pho Regulon Expression During Infection and Immune System Himentioning

confidence: 62%

Interplay between genetic regulation of phosphate homeostasis and bacterial virulence

2014

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Bacterial pathogens, including those of humans, animals, and plants, encounter phosphate (Pi)-limiting or Pi-rich environments in the host, depending on the site of infection. The environmental Pi-concentration results in modulation of expression of the Pho regulon that allows bacteria to regulate phosphate assimilation pathways accordingly. In many cases, modulation of Pho regulon expression also results in concomitant changes in virulence phenotypes. Under Pi-limiting conditions, bacteria use the transcriptional-response regulator PhoB to translate the Pi starvation signal sensed by the bacterium into gene activation or repression. This regulator is employed not only for the maintenance of bacterial Pi homeostasis but also to differentially regulate virulence. The Pho regulon is therefore not only a regulatory circuit of phosphate homeostasis but also plays an important adaptive role in stress response and bacterial virulence. Here we focus on recent findings regarding the mechanisms of gene regulation that underlie the virulence responses to Pi stress in Vibrio cholerae, Pseudomonas spp., and pathogenic E. coli.

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Expression, Purification, and Characterization of the Recombinant, Two-Component, Response Regulator ArlR from Fusobacterium nucleatum

Fan

Shi

et al. 2022

Appl Biochem Biotechnol

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Fusobacterium nucleatum is associated with the incidence and development of multiple diseases, such as periodontitis and colorectal cancer (CRC). Till now, studies have proved only a few proteins to be associated with such pathogenic diseases. The two-component system is one of the most prevalent forms of bacterial signal transduction related to intestinal diseases. Here we report a novel, recombinant, two-component, response-regulator protein ArlR from the genome of F. nucleatum strain ATCC 25586. We optimized the expression and puri cation conditions of ArlR; in addition, we characterized the interaction of this response regulator protein to the corresponding histidine kinase and DNA sequence. The fulllength ArlR was successfully expressed in six of the E. coli host strains. However, optimum expression conditions of ArlR were present only in E. coli strain BL21 Condon plus (DE3) RIL that was later induced with isopropyl β-D-1-thiogalactopyranoside (IPTG) for 8 h at 25 °C. The SDS-PAGE analysis revealed the molecular weight of the recombinant protein as 27.3 kDa and approximately 90% purity after gel ltration chromatography. ArlR was biologically active after its puri cation. Therefore, it accepted the corresponding phosphorylated histidine-kinase phosphate group and bound to the analogous DNA sequence. The binding constant between ArlR and the corresponding histidine kinase is 1.28 µM, while the binding constant between ArlR and the bound DNA sequence is 37.5 µM. Altogether, these results illustrate an effective expression and puri cation method for the novel two-component system protein ArlR.

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PhoB Regulates the Survival of Bacteroides fragilis in Peritoneal Abscesses

Cited by 14 publications

References 37 publications

PhoPR Contributes to Staphylococcus aureus Growth during Phosphate Starvation and Pathogenesis in an Environment-Specific Manner

PhoPR Contributes to Staphylococcus aureus Growth during Phosphate Starvation and Pathogenesis in an Environment-Specific Manner

Interplay between genetic regulation of phosphate homeostasis and bacterial virulence

Expression, Purification, and Characterization of the Recombinant, Two-Component, Response Regulator ArlR from Fusobacterium nucleatum

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