The Ferritin-Like Dps Protein Is Required for
 Salmonella enterica
 Serovar Typhimurium Oxidative Stress Resistance and Virulence

Halsey, Thomas A.; Vázquez‐Torres, Andrés; Gravdahl, Daniel J.; Fang, Ferric C.; Libby, Stephen J.

doi:10.1128/iai.72.2.1155-1158.2004

Cited by 142 publications

(132 citation statements)

References 30 publications

(27 reference statements)

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…The peroxiredoxin domain of PGdx has a role in protection (3,4,92). Similarly, in Salmonella enterica serovar Typhimurium, Dps protects against H 2 O 2 -derived oxidative stress and is needed for bacterial survival after phagocytosis by macrophages, as shown in a mouse model of infection (27). Dps' protective function is derived from its ability to bind Fe 2ϩ and abrogate H 2 O 2 -induced hydroxy radical production via the Fenton reaction; H 2 O 2 treatment of Fe 2ϩ -DNA complexes, in the absence of Dps, leads to the total degradation of the DNA (89).…”

Section: Resultsmentioning

confidence: 99%

“…Proteins involved in such processes include catalase, which decomposes H 2 O 2 , and members of both the AhpCF/TsaA family of alkylhydroperoxidases and the organic hydroperoxide resistance proteins (Ohr) that decompose organic peroxides. Also, DNA-binding ferritin-like proteins (Dps) sequester free iron and bind to DNA, thus protecting DNA from damage (27,33,45,53,59,60,67). In addition, many bacterial species possess genes encoding OxyR, a global regulator of antioxidant defenses (24, 66).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The OxyR Regulon in Nontypeable Haemophilus influenzae

et al. 2007

View full text Add to dashboard Cite

Nontypeable Haemophilus influenzae (NTHi) is a gram-negative bacterium and a common commensal organism of the upper respiratory tract in humans. NTHi causes a number of diseases, including otitis media, sinusitis, conjunctivitis, exacerbations of chronic obstructive pulmonary disease, and bronchitis. During the course of colonization and infection, NTHi must withstand oxidative stress generated by insult due to multiple reactive oxygen species produced endogenously by other copathogens and by host cells. Using an NTHi-specific microarray containing oligonucleotides representing the 1821 open reading frames of the recently sequenced NTHi isolate 86-028NP, we have identified 40 genes in strain 86-028NP that are upregulated after induction of oxidative stress due to hydrogen peroxide. Further comparisons between the parent and an isogenic oxyR mutant identified a subset of 11 genes that were transcriptionally regulated by OxyR, a global regulator of oxidative stress. Interestingly, hydrogen peroxide induced the OxyR-independent upregulation of expression of the genes encoding components of multiple iron utilization systems. This finding suggested that careful balancing of levels of intracellular iron was important for minimizing the effects of oxidative stress during NTHi colonization and infection and that there are additional regulatory pathways involved in iron utilization.In the evolution of life, a delicate physiological balance has arisen to compensate for both an organism's need for oxygen and the attendant lethal consequences of oxygen's toxicity. For example, in the electron transport chain, electrons can be inadvertently transferred from redox-active proteins to oxygen, producing reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H 2 O 2 ). The effects of ROS on cells can then be exacerbated by the presence of free iron which, via the Fenton reaction, can react with H 2 O 2 to produce more highly reactive hydroxyl radicals (34, 40, 52). Within a host, this problem is compounded by the release of extracellular ROS by phagocytes, which again, can have deleterious effects on invading pathogens (13). Thus, bacteria have evolved an array of increasingly well-defined mechanisms to abrogate the effects of oxidative stress. Proteins involved in such processes include catalase, which decomposes H 2 O 2 , and members of both the AhpCF/TsaA family of alkylhydroperoxidases and the organic hydroperoxide resistance proteins (Ohr) that decompose organic peroxides. Also, DNA-binding ferritin-like proteins (Dps) sequester free iron and bind to DNA, thus protecting DNA from damage (27,33,45,53,59,60,67). In addition, many bacterial species possess genes encoding OxyR, a global regulator of antioxidant defenses (24, 66).Protection against oxidative stress is especially important to nontypeable Haemophilus influenzae (NTHi). NTHi is one of three bacterial commensal organisms, the others being Streptococcus pneumoniae and Moraxella catarrhalis, which can ascend a virus-compromised eustachian tube and caus...

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

The OxyR Regulon in Nontypeable Haemophilus influenzae

et al. 2007

View full text Add to dashboard Cite

show abstract

“…H 2 O 2 ) (17)(18)(19)(20), nutrient starvation (13,15,21), and the presence of ethanol (15,16). Although Dps proteins are not essential for cell viability under normal growth conditions, it was shown that Dps deletion mutants of some bacteria are susceptible to oxidative stress (22)(23)(24), acids, bases, or UV radiation (25). Dps proteins can be induced by increasing iron concentrations in the medium (18) and may be up-regulated during iron starvation (19,26).…”

mentioning

confidence: 99%

Structure and Mechanism of Iron Translocation by a Dps Protein from Microbacterium arborescens

Pesek

Büchler

Albrecht

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Dps (DNA protection during starvation) enzymes are a major class of dodecameric proteins that bacteria use to detoxify their cytosol through the uptake of reactive iron species. In the stationary growth phase of bacteria, Dps enzymes are primarily used to protect DNA by biocrystallization. To characterize the wild type Dps protein from Microbacterium arborescens that displays additional catalytic functions (amide hydrolysis and synthesis), we determined the crystal structure to a resolution of 2.05 Å at low iron content. The structure shows a single iron at the ferroxidase center coordinated by an oxo atom, one water molecule, and three ligating residues. An iron-enriched protein structure was obtained at 2 Å and shows the stepwise uptake of two hexahydrated iron atoms moving along channels at the 3-fold axis before a restriction site inside the channels requires removal of the hydration sphere. Supporting biochemical data provide insight into the regulation of this acylamino acid hydrolase. Moreover, the peroxidase activity of the protein was determined. The influence of iron and siderophores on the expression of acylamino acid hydrolase was monitored during several stages of cell growth. Altogether our data provide an interesting view of an unusual Dps-like enzyme evolutionarily located apart from the large Dps sequence clusters.Iron is an essential element for cells as the cofactor in numerous enzymes. The element plays a fundamental role in cell respiration, for example as a component of cytochromes and iron-sulfur proteins. In addition, many processes such as photosynthesis, nitrogen fixation, and methanogenesis are strictly iron-dependent (1). Remarkably, iron of the two redox states differs in solubility: the reduced ferrous Fe 2ϩ form is soluble at 10 Ϫ1 M, whereas the oxidized ferric Fe 3ϩ species is highly insoluble at physiological pH.Bacteria regulate iron homeostasis using iron-sensing repressors such as Fur in Escherichia coli (1-3). Fur mainly regulates the synthesis and transport of siderophores, low molecular weight compounds with a high affinity for Fe 3ϩ that are secreted into the external medium (1). The poor bioavailability of iron often limits bacterial growth (1 Bacteria are protected against H 2 O 2 and ROS by different enzymes such as superoxide dismutases, superoxide reductases, catalases, and Dps proteins (DNA protection during starvation) (4). Dps proteins belong to the superfamily of the ferritin fold but, unlike the 24-mer ferritins, in prokaryotes they occur only as 12-meric complexes with a slightly variable architecture (5). They are active in Fe 2ϩ uptake, oxidation, storage, and H 2 O 2 destruction (1, 6, 7) and also provide physical protection by binding DNA and forming ordered material as shown for E. coli (8, 9), Bacillus cereus (10), and the marine cyanobacterium Trichodesmium erythraeum (11

show abstract

“…We also constructed sep22-defective Salmonella mutants and examined the correlation between expression of SEp22 and pathogenicity to BALB/c mice using these mutants together with the wild-type parental strain (12,13,Amano et al,manuscript in preparation). In the course of our study on SEp22, Halsey et al reported the involvement of Salmonella Dps in the pathogenicity of Salmonella infection in a gene-targeting study (7). However, regulation of SEp22 expression especially with respect to virulence of environmental isolates remains largely unknown.…”

Section: Introductionmentioning

confidence: 96%

“…We analyzed sequences of N-terminal 22 amino acids of SEp22, and performed cloning of the sep22 gene covering full length coding of nucleotide sequences corresponding to 168 amino acids. The sep22 gene was shown to be similar to E. coli dps/ pexB, and subsequently to be identical to Salmonella dps (7). We also constructed sep22-defective Salmonella mutants and examined the correlation between expression of SEp22 and pathogenicity to BALB/c mice using these mutants together with the wild-type parental strain (12,13,Amano et al,manuscript in preparation).…”

Section: Introductionmentioning

confidence: 99%

Expression and Degradation of SEp22, a Pathogenicity-Related Protein of Salmonella Dps, in Salmonella enterica serovar Enteritidis Isolated from the Poultry Farms in Japan

Terai

Yamasaki²,

Igimi³

et al. 2005

Bioscience Microflora

View full text Add to dashboard Cite

We isolated and characterized a pathogenicity-related protein in Salmonella enterica serovar Enteritidis (SE) from poultry farms, and designated it as SEp22, which has recently been identified with Salmonella Dps, a DNA-binding protein (12, 13, Amano et al., manuscript in preparation). Expression of SEp22 was shown to be transcriptionally regulated, because another SE strain without virulence was found to possess a full-length non-mutated gene of sep22, but had little expression of SEp22 mRNA and much lower levels of SEp22 protein compared to the virulent standard strain SE Cl#15-1. Besides, expression of SEp22 was connected with bacterial growth, showing reduced expression in the logarithmic phase but increased expression from the late logarithmic to stationary phases. These changes were slightly later than those in σ 38 levels as well as SEp22 mRNA, suggesting that expression of SEp22 is under transcriptional control through RNA polymerase activity by σ 38 . In addition, high levels of SEp22 in the stationary phase were rapidly reduced upon incubation of the bacteria in fresh medium. This reduction was dependent on bacterial concentration in the culture, temperature, and time of incubation, suggesting proteolytic degradation of SEp22 in growing bacteria.

show abstract

The Ferritin-Like Dps Protein Is Required for Salmonella enterica Serovar Typhimurium Oxidative Stress Resistance and Virulence

Cited by 142 publications

References 30 publications

The OxyR Regulon in Nontypeable Haemophilus influenzae

The OxyR Regulon in Nontypeable Haemophilus influenzae

Structure and Mechanism of Iron Translocation by a Dps Protein from Microbacterium arborescens

Expression and Degradation of SEp22, a Pathogenicity-Related Protein of <i>Salmonella</i> Dps, in <i>Salmonella enterica</i> serovar Enteritidis Isolated from the Poultry Farms in Japan

Contact Info

Product

Resources

About