DsbM affects aminoglycoside resistance in<i>Pseudomonas aeruginosa</i>by the reduction of OxyR

Li, Mingxuan; Guan, Xidong; Wang, Xuehan; Xu, Haijin; Bai, Yanling; Zhang, Xiuming; Qiao, Mingqiang

doi:10.1111/1574-6968.12384

Cited by 7 publications

(5 citation statements)

References 20 publications

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“…Given the cellular location of DsbM, DsbM should acquire its reducing power from the cytosolic glutathione pool. Considering both the results in this paper and previously reported data on the reduction of DsbM by OxyR (Li et al, 2014), we propose an mechanism of action for DsbM in which the oxidized OxyR and the reduced glutathione are shuttled on the glutathione-binding site (or putative substrate-binding region) of DsbM (Fig. 7).…”

Section: Discussionsupporting

confidence: 73%

“…In the absence of hydrogen peroxide, OxyR returns to its reduced form (inactive state) through cellular reducing agents, such as glutathione (Toledano et al, 1994;Storz & Tartaglia, 1992;Jo et al, 2015;Choi et al, 2001). The interaction between DsbM and OxyR was confirmed through a yeast two-hybrid screen, and DsbM showed increased reduction of OxyR in P. aeruginosa (Li et al, 2014;Wang et al, 2012). In particular, it was reported that aminoglycoside resistance was increased in P. aeruginosa when dsbM was deleted.…”

Section: Introductionmentioning

confidence: 79%

“…Although DsbM has been implicated in the reduction of oxidized OxyR in P. aeruginosa (Li et al, 2014;Wang et al, 2012), its role remains ambiguous. We found that the fluorescence from the tryptophan residue was highly quenched when the DsbM protein was oxidized, presumably because the disulfide bond in the CXXC motif quenched the fluorescence from Trp16 in the CXXC motif.…”

Section: Selective Reduction Of the Disulfide Bond Of Oxyr By Dsbmmentioning

confidence: 99%

“…Oxidized DsbM was found to be reduced by cellular glutathiones. Furthermore, DsbM has been implicated in the reduction of the peroxide-dependent transcription factor OxyR in the bacterial cytoplasm (Li et al, 2014;Wang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Crystal structures of the disulfide reductase DsbM from Pseudomonas aeruginosa

Park

Chung

et al. 2016

Acta Cryst Sect D Struct Biol

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In bacteria, many Dsb-family proteins play diverse roles in the conversion between the oxidized and reduced states of cysteine residues of substrate proteins. Most Dsb enzymes catalyze disulfide formation in periplasmic or secreted substrate proteins. Recently, a DsbM protein has been found in a Gram-negative bacterium, and was characterized as a cytosolic Dsb member with the conserved CXXC motif on the basis of sequence homology to the Dsb-family proteins. The protein was implicated in the reduction of the cytoplasmic redox-sensor protein OxyR in Pseudomonas aeruginosa. Here, crystal structures of DsbM from P. aeruginosa are presented, revealing that it consists of a modified thioredoxin domain containing the CXXC motif and a lid domain surrounding the CXXC motif. In a glutathione-linked structure, a glutathione molecule is linked to the CXXC motif of DsbM and is bound in an elongated cavity region in the thioredoxin domain, which is also suited for substrate peptide binding. A striking structural similarity to a human glutathione S-transferase was found in the glutathione-binding pocket. Further, biochemical evidence is presented suggesting that DsbM is directly involved in the reduction of the disulfide of Cys199 and Cys208 in OxyR, resulting in the acceleration of OxyR reduction in the absence of reactive oxygen species stress. These findings may help to expand the understanding of the diverse roles of redox-related proteins that contain the CXXC motif.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 79%

Section: Selective Reduction Of the Disulfide Bond Of Oxyr By Dsbmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Crystal structures of the disulfide reductase DsbM from Pseudomonas aeruginosa

Park

Chung

et al. 2016

Acta Cryst Sect D Struct Biol

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“…Suggesting a possible connection between GSH and Dsb proteins in the periplasm, a new Dsb member, DsbM, was described in Pseudomonas aeruginosa which has structural similarity to DsbA and, to a lesser extent, to the Trx-domain of DsbC (134). While DsbM is cytoplasmic, it was reported to have a GSHdependent reductase activity against an oxidized OxyR mechanism of direct regulation of OxyR by reduction (135,136), suggesting that well-known Dsb proteins such as DsbA and DsbC may have GSH-dependent mechanisms that are still undisclosed. The dsbC gene is in a bi-cistronic operon with the downstream gene recJ, which encodes a 5′→3′ exonuclease.…”

Section: Isomerization Of Mismatched Disulfides and Protection Of Lonmentioning

confidence: 99%

Disulfide Bond Formation in the Periplasm of Escherichia coli

2019

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The formation of disulfide bonds is critical to the folding of many extracytoplasmic proteins in all domains of life. With the discovery in the early 1990s that disulfide bond formation is catalyzed by enzymes, the field of oxidative folding of proteins was born. Escherichia coli played a central role as a model organism for the elucidation of the disulfide bond-forming machinery. Since then, many of the enzymatic players and their mechanisms of forming, breaking, and shuffling disulfide bonds have become understood in greater detail. This article summarizes the discoveries of the past 3 decades, focusing on disulfide bond formation in the periplasm of the model prokaryotic host E. coli.

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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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DsbM affects aminoglycoside resistance inPseudomonas aeruginosaby the reduction of OxyR

Cited by 7 publications

References 20 publications

Crystal structures of the disulfide reductase DsbM from Pseudomonas aeruginosa

Crystal structures of the disulfide reductase DsbM from Pseudomonas aeruginosa

Disulfide Bond Formation in the Periplasm of Escherichia coli

Peroxide‐Sensing Transcriptional Regulators in Bacteria

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