TY - JOUR
T1 - Pseudomonas aeruginosa Thiol Peroxidase Protects against Hydrogen Peroxide Toxicity and Displays Atypical Patterns of Gene Regulation
AU - Somprasong, Nawarat
AU - Jittawuttipoka, Thichakorn
AU - Duang-Nkern, Jintana
AU - Romsang, Adisak
AU - Chaiyen, Pimchai
AU - Schweizer, Herbert P.
AU - Vattanaviboon, Paiboon
AU - Mongkolsuk, Skorn
N1 - Funding Information:
This work was supported by grants from the Fondation pour la Recherche Médicale (Programme “équipe FRM,” DEQ20120323700) and the Agence Nationale de la Recherche (ANR) (ANR-08-MNP-030) to A.C. It was performed in the frame of the LABEX LIFESENSES (reference ANR-10-LABX-65) supported by French state funds managed by the ANR within the Investissements d’Avenir program under reference ANR-11-IDEX-0004-02. P.Z. was the recipient of a postdoctoral fellowship from the Région ile de France (Neuropole). H.B. is the recipient of an École des Neurosciences de Paris (ENP) Graduate Program fellowship from the ENP and the Région Ile-de-France (DIM Cerveau et Pensée). A.P. is a recipient of a fellowship under the Investissements d’Avenir program (ANR-10-LABX-54 MEMO LIFE). Z.W. was supported in part by a Bristol-Myers Squibb Postdoctoral Fellowship at the Rockefeller University.
PY - 2012/8
Y1 - 2012/8
N2 - The Pseudomonas aeruginosa PAO1 thiol peroxidase homolog (Tpx) belongs to a family of enzymes implicated in the removal of toxic peroxides. We have shown the expression of tpx to be highly inducible with redox cycling/superoxide generators and diamide and weakly inducible with organic hydroperoxides and hydrogen peroxide (H2O2). The PAO1 tpx pattern is unlike the patterns for other peroxide-scavenging genes in P. aeruginosa. Analysis of the tpx promoter reveals the presence of a putative IscR binding site located near the promoter. The tpx expression profiles in PAO1 and the iscR mutant, together with results from gel mobility shift assays showing that purified IscR specifically binds the tpx promoter, support the role of IscR as a transcriptional repressor of tpx that also regulates the oxidant-inducible expression of the gene. ecombinant Tpx has been purified and biochemically characterized. The enzyme catalyzes thioredoxin-dependent peroxidation and can utilize organic hydroperoxides and H2O2 as substrates. The Δtpx mutant demonstrates differential sensitivity to H2O2 only at moderate concentrations (0.5 mM) and not at high (20 mM) concentrations, suggesting a novel protective role of tpx against H2O2 in P. aeruginosa. Altogether, P. aeruginosa tpx is a novel member of the IscR regulon and plays a primary role in protecting the bacteria from submillimolar concentrations of H2O2.
AB - The Pseudomonas aeruginosa PAO1 thiol peroxidase homolog (Tpx) belongs to a family of enzymes implicated in the removal of toxic peroxides. We have shown the expression of tpx to be highly inducible with redox cycling/superoxide generators and diamide and weakly inducible with organic hydroperoxides and hydrogen peroxide (H2O2). The PAO1 tpx pattern is unlike the patterns for other peroxide-scavenging genes in P. aeruginosa. Analysis of the tpx promoter reveals the presence of a putative IscR binding site located near the promoter. The tpx expression profiles in PAO1 and the iscR mutant, together with results from gel mobility shift assays showing that purified IscR specifically binds the tpx promoter, support the role of IscR as a transcriptional repressor of tpx that also regulates the oxidant-inducible expression of the gene. ecombinant Tpx has been purified and biochemically characterized. The enzyme catalyzes thioredoxin-dependent peroxidation and can utilize organic hydroperoxides and H2O2 as substrates. The Δtpx mutant demonstrates differential sensitivity to H2O2 only at moderate concentrations (0.5 mM) and not at high (20 mM) concentrations, suggesting a novel protective role of tpx against H2O2 in P. aeruginosa. Altogether, P. aeruginosa tpx is a novel member of the IscR regulon and plays a primary role in protecting the bacteria from submillimolar concentrations of H2O2.
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U2 - 10.1128/JB.00347-12
DO - 10.1128/JB.00347-12
M3 - Article
C2 - 22609922
AN - SCOPUS:84866342431
SN - 0021-9193
VL - 194
SP - 3904
EP - 3912
JO - Journal of Bacteriology
JF - Journal of Bacteriology
IS - 15
ER -