Oxidative stress and metal ions regulate a ferritin-like gene, dpr, in Streptococcus pyogenes

Tsou, Chih Cheng; Chiang-Ni, Chuan; Lin, Yee Shin; Chuang, Woei Jer; Lin, Ming Tsan; Liu, Ching Chuan; Wu, Jiunn Jong

doi:10.1016/j.ijmm.2009.09.002

Cited by 29 publications

(29 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we confirm that pmtA expression is upregulated by both Fe(II) and hydrogen peroxide and is regulated via PerR. The GAS ferritin-like protein Dpr (formerly MrgA) is also regulated by PerR (14) and has been shown to chelate Fe and protect GAS under conditions of oxidative stress (46). We hypothesize that GAS uses Dpr and PmtA to sequester and export Fe(II) under oxidative stress conditions, respec-tively.…”

Section: Discussionsupporting

confidence: 73%

The PerR-Regulated P _1B-4 -Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes

et al. 2017

View full text Add to dashboard Cite

Streptococcus pyogenes (group A Streptococcus [GAS]) is an obligate human pathogen responsible for a broad spectrum of human disease. GAS has a requirement for metal homeostasis within the human host and, as such, tightly modulates metal uptake and efflux during infection. Metal acquisition systems are required to combat metal sequestration by the host, while metal efflux systems are essential to protect against metal overload poisoning. Here, we investigated the function of PmtA (PerRregulated metal transporter A), a P 1B-4 -type ATPase efflux pump, in invasive GAS M1T1 strain 5448. We reveal that PmtA functions as a ferrous iron [Fe(II)] efflux system. In the presence of high Fe(II) concentrations, the 5448ΔpmtA deletion mutant exhibited diminished growth and accumulated 5-fold-higher levels of intracellular Fe(II) than did the wild type and the complemented mutant. The 5448ΔpmtA deletion mutant also showed enhanced susceptibility to killing by the Fe-dependent antibiotic streptonigrin as well as increased sensitivity to hydrogen peroxide and superoxide. We suggest that the PerRmediated control of Fe(II) efflux by PmtA is important for bacterial defense against oxidative stress. PmtA represents an exemplar for an Fe(II) efflux system in a host-adapted Gram-positive bacterial pathogen.KEYWORDS iron efflux, PmtA, oxidative stress response, PerR, group A Streptococcus, Streptococcus pyogenes D efense against peroxide is recognized as one of the most widespread stress responses in prokaryotes. A characteristic of the peroxide stress response is the increased expression of peroxidases that can directly remove hydrogen peroxide as well as the induction of systems that can repair damaged proteins and nucleic acids (1, 2). Streptococcus pyogenes (group A Streptococcus [GAS]) coordinates oxidative stress responses through the action of the regulator PerR, which functions as a repressor of oxidative stress defense genes under normal conditions through binding to DNA at per boxes upstream of these genes (3, 4). This stable complex typically exists with Fe as a prosthetic group; in the presence of hydrogen peroxide, Fe causes metal-catalyzed oxidation and damage of the complex, leading to its dissociation and the subsequent transcription of peroxide response genes (3-6). In GAS, the PerR-regulated oxidative stress response encompasses both direct mechanisms, involving the detoxification of reactive oxygen species (ROS), and indirect mechanisms, which involve the repair of biomolecules damaged by oxidative stress. Direct mechanisms involving the enzymatic detoxification of reactive oxygen species are achieved through alkyl hydroperoxidases and glutathione peroxidases (1, 2, 5) as well as a single superoxide dismutase, SodA, which is Mn dependent (7). An example of an indirect response mechanism is PolAI, a DNA polymerase that repairs oxidatively damaged DNA (8).

show abstract

Section: Discussionsupporting

confidence: 73%

The PerR-Regulated P _1B-4 -Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The bacterial strains S. pyogenes A-20 (M1 serotype) and perR deficient mutant (SW-612) were described previously (21). Two S. pyogenes strains were cultured in trypticase soy broth containing 0.5% yeast extract (TSBYE) supplemented with protease inhibitor mixture (PIC) without agitation at 37°C.…”

Section: Bacterial Strains Growth Conditions and Sample Preparation-mentioning

confidence: 99%

“…The resulting construction was designated Plasmid 6625. Electroporation of this plasmid into the strain A-20 was conducted by the standard protocol described previously (21).…”

Section: Bacterial Strains Growth Conditions and Sample Preparation-mentioning

confidence: 99%

“…However, the mechanism by which PerR contributes to S. pyogenes virulence and the specific contribution of PerR-regulated protein expression to bacterial survival at particular host sites during infection remains unknown. The construction of the strain SW-612 has been previously described in detail (21). The expression levels of the perR gene products in strain SW-612 were also determined for virulence evaluation in the present study.…”

Section: Validation Of Characteristics Of the Perr Deficient Mutant-mentioning

confidence: 99%

“…The recombinant His6-tagged PerR was expressed and purified under native conditions. The estimated size of r-PerR with tag was 19 kDa (21). A 428-bp upstream region containing the Per-like box (TTTTATTAATTTTAA) of the mf3 gene was amplified by PCR.…”

Section: Summary Of Differentially Expressed Protein Spots On Two-dimmentioning

confidence: 99%

See 2 more Smart Citations

Differential Secretomics of Streptococcus pyogenes Reveals a Novel Peroxide Regulator (PerR)-regulated Extracellular Virulence Factor Mitogen Factor3 (MF3)

Wen

Tsou

Kuo

et al. 2011

Molecular & Cellular Proteomics

Self Cite

View full text Add to dashboard Cite

Streptococcus pyogenes is a human pathogen that causes various diseases. Numerous virulence factors secreted by S. pyogenes are involved in pathogenesis. The peroxide regulator (PerR) is associated with the peroxide resistance response and pathogenesis, but little is known about the regulation of the secretome involved in virulence. To investigate how PerR regulates the expression of the S. pyogenes secretome involved in virulence, a perR deficient mutant was used for comparative secretomic analysis with a wild-type strain. The conditioned medium containing secreted proteins of a wild-type strain and a perR deficient mutant at the stationary phase were collected for two-dimensional gel electrophoresis analysis, where protease inhibitors were applied to avoid the degradation of extracellular proteins. Differentially expressed protein spots were identified by liquid chromatography electrospray ionization tandem MS. More than 330 protein spots were detected on each gel. We identified 25 unique up-regulated proteins and 13 unique downregulated proteins that were directly or indirectly controlled by the PerR regulator. Among these identified proteins, mitogen factor 3 (MF3), was selected to verify virulence and the expression of gene products. The data showed that MF3 protein levels in conditioned medium, as measured by immunoblot analysis, correlated well with protein levels determined by two-dimensional gel electrophoresis analysis. We also demonstrated that PerR bound to the promoter region of the mf3 gene. The result of an infection model showed that virulence was attenuated in the mf3 deficient mutant. Additional growth data of the wild-type strain and the mf3 deficient mutant suggested that MF3 played a role in digestion of exogenous DNA for promoting growth. To summarize, we conclude that PerR can positively regulate the expression of the secreted protein MF3 that contributes to the virulence in S. pyogenes. The analysis of the PerR-regulated secretome provided key information for the elucidation of the host-pathogen interactions and might assist in the

show abstract

Virulence factors of Streptococcus pyogenes strains from women in peri-labor with invasive infections

Golińska

Linden

Więcek

et al. 2016

Eur J Clin Microbiol Infect Dis

View full text Add to dashboard Cite

Invasive group A streptococcal (GAS) infections constitute an important epidemiological problem. Many cases occur in women during the postnatal period. The objective of this study was to evaluate the presence of the genes responsible for production of iron-chelating protein (perR) and superantigens (speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ, and ssa) in S. pyogenes strains isolated from invasive infections in women after delivery. Furthermore, this study sought to verify whether S. pyogenes strains show special phenotypic and genotypic (sla, spy1325) characteristics that may play a decisive role in adherence to the genital tract epithelium. Moreover, the emm-types and antibiotic susceptibility were determined. We tested 30 invasive S. pyogenes strains isolated from postpartum invasive infection and 37 GAS control strains isolated from the genital tracts of asymptomatic multiparous women. The majority of the tested strains were shown to express two types of emm genes (1 and 28), though emm −12, −28, −75 and −89 were uniquely expressed in the group of strains isolated from invasive infections. A significantly higher prevalence of perR in the strains from puerperal fever was shown. Significant differences were also found between the two groups with respect to the incidence of the genes related to adherence; GAS strains originating from women with sepsis/puerperal fever showed presence of these genes less frequently than those of the control group. Although differences in frequencies of the gene coding for various superantigens were noted between the compared groups of GAS strains, they were not significant.

show abstract

Oxidative stress and metal ions regulate a ferritin-like gene, dpr, in Streptococcus pyogenes

Cited by 29 publications

References 40 publications

The PerR-Regulated P _1B-4 -Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes

The PerR-Regulated P _1B-4 -Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes

Differential Secretomics of Streptococcus pyogenes Reveals a Novel Peroxide Regulator (PerR)-regulated Extracellular Virulence Factor Mitogen Factor3 (MF3)

Virulence factors of Streptococcus pyogenes strains from women in peri-labor with invasive infections

Contact Info

Product

Resources

About

Oxidative stress and metal ions regulate a ferritin-like gene, dpr, in Streptococcus pyogenes

Cited by 29 publications

References 40 publications

The PerR-Regulated P 1B-4 -Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes

The PerR-Regulated P 1B-4 -Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes

Differential Secretomics of Streptococcus pyogenes Reveals a Novel Peroxide Regulator (PerR)-regulated Extracellular Virulence Factor Mitogen Factor3 (MF3)

Virulence factors of Streptococcus pyogenes strains from women in peri-labor with invasive infections

Contact Info

Product

Resources

About

The PerR-Regulated P _1B-4 -Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes

The PerR-Regulated P _1B-4 -Type ATPase (PmtA) Acts as a Ferrous Iron Efflux Pump in Streptococcus pyogenes