Novel DNA binding protein SarZ contributes to virulence in <i>Staphylococcus aureus</i>

Kaito, Chikara; Morishita, Daisuke; Matsumoto, Yasuhiko; Kurokawa, Kenji; Sekimizu, Kazuhisa

doi:10.1111/j.1365-2958.2006.05480.x

Cited by 95 publications

(89 citation statements)

References 44 publications

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“…Kaito et al identified SarZ (Kaito et al, 2006), based on its ability to restore hemolysis activity in a S. aureus cvfA mutant defective in hla expression. A sarZ mutant of RN4220 had attenuated virulence in both silk worm and mouse infection models.…”

Section: C Other Sara Homologsmentioning

confidence: 99%

The SarA protein family of Staphylococcus aureus

Cheung

Nishina

Trotonda

et al. 2008

The International Journal of Biochemistry & Cell Biology

174

172

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Staphylococcus aureus is widely appreciated as an opportunistic pathogen, primarily in hospitalrelated infections. However, recent reports indicate that S. aureus infections can now occur in other wise healthy individuals in the community setting. The success of this organism can be attributed to the large array of regulatory proteins, including the SarA protein family, used to respond to changing microenvironments. Sequence alignment and structural data reveal that the SarA protein family can be divided into three subfamilies: 1) single domain proteins; 2) double domain proteins and 3) MarR homologs. Structural studies have also demonstrated that SarA, SarR, SarS, MgrA, and thus possibly all members of this protein family are winged helix proteins with minor variations. Mutagenesis studies of SarA disclose that the winged helix motifs are important for DNA binding and function. Recent progress concerning the functions and plausible mechanisms of regulation of SarA and its homologs are discussed.

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Section: C Other Sara Homologsmentioning

confidence: 99%

The SarA protein family of Staphylococcus aureus

Cheung

Nishina

Trotonda

et al. 2008

The International Journal of Biochemistry & Cell Biology

174

172

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“…Other members of the group include Pseudomonas aeruginosa OspR (63) and MgrA and SarZ in Staphylococcus aureus (54,73). All sense peroxides or other oxidants through the initial oxidation of a sensing cysteine residue (15,16,63).…”

Section: Ohrrmentioning

confidence: 99%

Peroxide‐Sensing Transcriptional Regulators in Bacteria

Dubbs

Mongkolsuk

2016

Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria

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The ability to maintain intracellular concentrations of toxic reactive oxygen species (ROS) within safe limits is essential for all aerobic life forms. In bacteria, as well as other organisms, ROS are produced during the normal course of aerobic metabolism, necessitating the constitutive expression of ROS scavenging systems. However, bacteria can also experience transient high-level exposure to ROS derived either from external sources, such as the host defense response, or as a secondary effect of other seemingly unrelated environmental stresses. Consequently, transcriptional regulators have evolved to sense the levels of ROS and coordinate the appropriate oxidative stress response. Three well-studied examples of these are the peroxide responsive regulators OxyR, PerR, and OhrR. OxyR and PerR are sensors of primarily H 2 O 2 , while OhrR senses organic peroxide (ROOH) and sodium hypochlorite (NaOCl). OxyR and OhrR sense oxidants by means of the reversible oxidation of specific cysteine residues. In contrast, PerR senses H 2 O 2 via the Fe-catalyzed oxidation of histidine residues. These transcription regulators also influence complex biological phenomena, such as biofilm formation, the evasion of host immune responses, and antibiotic resistance via the direct regulation of specific proteins.

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“…Transcription profiling identified sarZ as a regulator of metabolic processes, antibiotic resistance, autolysis, peroxide response, and virulence (4). In studies using silkworm and mouse infection models, a sarZ mutant strain produced less hemolysin and exhibited less virulence than the wild-type strain (6). Most recently, SarZ has been identified as a regulator important for the spread of active infections, influencing toxin and protease production (7,8).…”

mentioning

confidence: 99%

“…aureus SarZ is a transcriptional regulator that has affinity for various promoter fragments, including those of ohr, hla, and agr, genes involved in organic hydroperoxide resistance, hemolysin production, and virulence regulation, respectively (4,6). Transcription profiling identified sarZ as a regulator of metabolic processes, antibiotic resistance, autolysis, peroxide response, and virulence (4).…”

mentioning

confidence: 99%

Crystal Structures of the Reduced, Sulfenic Acid, and Mixed Disulfide Forms of SarZ, a Redox Active Global Regulator in Staphylococcus aureus

Poor¹,

Chen²,

Duguid

et al. 2009

Journal of Biological Chemistry

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SarZ is a global transcriptional regulator that uses a single cysteine residue, Cys 13 , to sense peroxide stress and control metabolic switching and virulence in Staphylococcus aureus. SarZ belongs to the single-cysteine class of OhrR-MgrA proteins that play key roles in oxidative resistance and virulence regulation in various bacteria. We present the crystal structures of the reduced form, sulfenic acid form, and mixed disulfide form of SarZ. Both the sulfenic acid and mixed disulfide forms are structurally characterized for the first time for this class of proteins. The Cys 13 sulfenic acid modification is stabilized through two hydrogen bonds with surrounding residues, and the overall DNA-binding conformation is retained. A further reaction of the Cys 13 sulfenic acid with an external thiol leads to formation of a mixed disulfide bond, which results in an allosteric change in the DNA-binding domains, disrupting DNA binding. Thus, the crystal structures of SarZ in three different states provide molecular level pictures delineating the mechanism by which this class of redox active regulators undergoes activation. These structures help to understand redox-mediated virulence regulation in S. aureus and activation of the MarR family proteins in general.

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Novel DNA binding protein SarZ contributes to virulence in Staphylococcus aureus

Cited by 95 publications

References 44 publications

The SarA protein family of Staphylococcus aureus

The SarA protein family of Staphylococcus aureus

Peroxide‐Sensing Transcriptional Regulators in Bacteria

Crystal Structures of the Reduced, Sulfenic Acid, and Mixed Disulfide Forms of SarZ, a Redox Active Global Regulator in Staphylococcus aureus

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