Staphylococcus aureus PerR Is a Hypersensitive Hydrogen Peroxide Sensor using Iron-mediated Histidine Oxidation

Ji, Chang-Jun; Kim, Jung-Hoon; Won, Young-Bin; Lee, Yeh-Eun; Choi, Tae-Woo; Ju, Shinyeong; Youn, Hwan; Helmann, John D.; Lee, Jinwon

doi:10.1074/jbc.m115.664961

Cited by 54 publications

(70 citation statements)

References 42 publications

(69 reference statements)

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“…The ability of Mn(II) and Fe(II) to bind to similar sites in proteins is well documented (Helmann, 2014;Huang et al, 2014;Imlay, 2014), and in some cases both cofactored forms of the protein retain activity. Examples include so-called cambialistic SODs (Abreu and Cabelli, 2010), the metalloregulatory protein PerR (Lee and Helmann, 2006;Ji et al, 2015;Turner et al, 2015), and some mononuclear Fe(II) enzymes (Anjem and Imlay, 2012). In other cases, binding of Mn(II) may lead to enzyme inhibition.…”

Section: Discussionmentioning

confidence: 99%

Bacillus subtilis MntR coordinates the transcriptional regulation of manganese uptake and efflux systems

Huang

Shin

Pinochet-Barros

et al. 2016

Molecular Microbiology

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104

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Summary The Bacillus subtilis MntR metalloregulatory protein senses manganese, an essential element required for central metabolism, oxidative stress resistance and replication. An mntR null mutant is highly sensitive to Mn(II) intoxication, which is attributed in part to the constitutive expression of two importers: the proton-dependent NRAMP family transporter MntH and the ABC transporter MntABCD. Here, we show that an mntR null mutant is still sensitive to Mn(II) intoxication even if both of the import systems are absent. This Mn(II) sensitivity results from the requirement for MntR to activate the transcription of two genes encoding cation diffusion facilitator (CDF) family efflux pumps. Physiological studies indicate that MneP (formerly YdfM) serves as the primary Mn(II) efflux pump with MneS (formerly YeaB) playing a secondary role. Mutant strains lacking mneP are Mn(II) sensitive and accumulate elevated levels of Mn(II), and these effects are exacerbated in a mneP mneS double mutant. DNA-binding and in vitro transcription studies demonstrate that MntR binds to both the mneP and mneS regulatory regions and directly activates transcription in response to levels of Mn(II) several-fold higher than required for repression of import genes. These results highlight the delicate balance of Mn(II) uptake and efflux systems controlled by MntR.

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Section: Discussionmentioning

confidence: 99%

Bacillus subtilis MntR coordinates the transcriptional regulation of manganese uptake and efflux systems

Huang

Shin

Pinochet-Barros

et al. 2016

Molecular Microbiology

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104

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“…In B. subtilis , hemEHY is induced anaerobically and hemAXCBL is induced by peroxide through de-repression of PerR [38,68]. As in B. subtilis , PerR has been implicated as a regulator of the hemEHY operon in Staphylococcus aureus ; yet recent work has demonstrated that major differences exist between B. subtilis and S. aureus PerR orthologs, and therefore, it is difficult to conclude that PerR plays a role in S. aureus heme synthesis [69,70]. Corynebacterium diphtheriae , a member of the Actinobacteria phylum, encodes two heme-responsive two-component systems (TCS).…”

Section: Bacterial Heme Synthesismentioning

confidence: 99%

Heme Synthesis and Acquisition in Bacterial Pathogens

Choby

Skaar

2016

Journal of Molecular Biology

256

266

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Bacterial pathogens require the iron-containing cofactor heme to cause disease. Heme is essential to the function of hemoproteins, which are involved in energy generation by the electron transport chain, detoxification of host immune effectors, and other processes. During infection, bacterial pathogens must synthesize heme or acquire heme from the host; however, host heme is sequestered in high-affinity hemoproteins. Pathogens have evolved elaborate strategies to acquire heme from host sources, particularly hemoglobin, and both heme acquisition and synthesis are important for pathogenesis. Paradoxically, excess heme is toxic to bacteria and pathogens must rely on heme detoxification strategies. Heme is a key nutrient in the struggle for survival between host and pathogen, and its study has offered significant insight into the molecular mechanisms of bacterial pathogenesis.

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“…In addition to Cys residues, iron is frequently used by regulatory proteins to sense O 2 , NO·, carbon monoxide (CO), O 2 · − , or redox cycling compounds. Iron can be found as (i) mononuclear centers in Fur, PerR (peroxide regulator) or NorR (nitric oxide regulator), (ii) [2Fe-2S] and [4Fe-4S] clusters in SoxR (superoxide regulator), FNR (fumarate-nitrate reduction regulator) or NsrR (nitric oxide-responsive regulator), or (iii) heme prosthetic groups in dormancy survival regulatory proteins DosT and DosS, or DNR (dissimilative nitrate respiration regulator) (Crack et al, 2014; Ji et al, 2015; Lobato et al, 2014; Ma et al, 2012). Molecular mechanisms of redox sensing rely on protein conformational changes triggered by interaction with reactive oxygen and nitrogen species (see accompanying review in this issue, Fang et al, 2016) (Figure 2B).…”

Section: Stresses In the Host Environmentmentioning

confidence: 99%

Bacterial Stress Responses during Host Infection

Fang

Frawley

Tapscott

et al. 2016

Cell Host & Microbe

259

224

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Pathogenic bacteria must withstand diverse host environments during infection. Environmental signals, such as pH, temperature, nutrient scarcity, etc., not only trigger adaptive responses within bacteria to these specific stress conditions but also direct the expression of virulence genes at an appropriate time and place. An appreciation of stress responses and their regulation is therefore essential for an understanding of bacterial pathogenesis. This review considers specific stresses in the host environment and their relevance to pathogenesis, with a particular focus on the enteric pathogen Salmonella.

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Staphylococcus aureus PerR Is a Hypersensitive Hydrogen Peroxide Sensor using Iron-mediated Histidine Oxidation

Cited by 54 publications

References 42 publications

Bacillus subtilis MntR coordinates the transcriptional regulation of manganese uptake and efflux systems

Bacillus subtilis MntR coordinates the transcriptional regulation of manganese uptake and efflux systems

Heme Synthesis and Acquisition in Bacterial Pathogens

Bacterial Stress Responses during Host Infection

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