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YjcC, a c-di-GMP phosphodiesterase protein, regulates the oxidative stress response and virulence of Klebsiella pneumoniae CG43.

Identifieur interne : 000690 ( Main/Exploration ); précédent : 000689; suivant : 000691

YjcC, a c-di-GMP phosphodiesterase protein, regulates the oxidative stress response and virulence of Klebsiella pneumoniae CG43.

Auteurs : Ching-Jou Huang [République populaire de Chine] ; Zhe-Chong Wang ; Hsi-Yuan Huang ; Hsien-Da Huang ; Hwei-Ling Peng

Source :

RBID : pubmed:23935824

Descripteurs français

English descriptors

Abstract

This study shows that the expression of yjcC, an in vivo expression (IVE) gene, and the stress response regulatory genes soxR, soxS, and rpoS are paraquat inducible in Klebsiella pneumoniae CG43. The deletion of rpoS or soxRS decreased yjcC expression, implying an RpoS- or SoxRS-dependent control. After paraquat or H2O2 treatment, the deletion of yjcC reduced bacterial survival. These effects could be complemented by introducing the ΔyjcC mutant with the YjcC-expression plasmid pJR1. The recombinant protein containing only the YjcC-EAL domain exhibited phosphodiesterase (PDE) activity; overexpression of yjcC has lower levels of cyclic di-GMP. The yjcC deletion mutant also exhibited increased reactive oxygen species (ROS) formation, oxidation damage, and oxidative stress scavenging activity. In addition, the yjcC deletion reduced capsular polysaccharide production in the bacteria, but increased the LD50 in mice, biofilm formation, and type 3 fimbriae major pilin MrkA production. Finally, a comparative transcriptome analysis showed 34 upregulated and 29 downregulated genes with the increased production of YjcC. The activated gene products include glutaredoxin I, thioredoxin, heat shock proteins, chaperone, and MrkHI, and proteins for energy metabolism (transporters, cell surface structure, and transcriptional regulation). In conclusion, the results of this study suggest that YjcC positively regulates the oxidative stress response and mouse virulence but negatively affects the biofilm formation and type 3 fimbriae expression by altering the c-di-GMP levels after receiving oxidative stress signaling inputs.

DOI: 10.1371/journal.pone.0066740
PubMed: 23935824
PubMed Central: PMC3720812


Affiliations:


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Le document en format XML

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<term>Bacterial Capsules (drug effects)</term>
<term>Bacterial Capsules (metabolism)</term>
<term>Bacterial Proteins (metabolism)</term>
<term>Base Sequence (MeSH)</term>
<term>Biofilms (drug effects)</term>
<term>Cyclic GMP (analogs & derivatives)</term>
<term>Cyclic GMP (metabolism)</term>
<term>Down-Regulation (drug effects)</term>
<term>Down-Regulation (genetics)</term>
<term>Female (MeSH)</term>
<term>Fimbriae, Bacterial (drug effects)</term>
<term>Fimbriae, Bacterial (metabolism)</term>
<term>Gene Deletion (MeSH)</term>
<term>Gene Expression Regulation, Bacterial (drug effects)</term>
<term>Klebsiella Infections (microbiology)</term>
<term>Klebsiella Infections (pathology)</term>
<term>Klebsiella pneumoniae (enzymology)</term>
<term>Klebsiella pneumoniae (genetics)</term>
<term>Klebsiella pneumoniae (pathogenicity)</term>
<term>Klebsiella pneumoniae (physiology)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred BALB C (MeSH)</term>
<term>Molecular Sequence Data (MeSH)</term>
<term>Oxidative Stress (MeSH)</term>
<term>Paraquat (toxicity)</term>
<term>Phosphoric Diester Hydrolases (metabolism)</term>
<term>Polysaccharides, Bacterial (metabolism)</term>
<term>Transcriptome (genetics)</term>
<term>Up-Regulation (drug effects)</term>
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<term>Capsules bactériennes (métabolisme)</term>
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<term>Fimbriae bactériens (métabolisme)</term>
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<term>Infections à Klebsiella (microbiologie)</term>
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<term>Régulation négative (effets des médicaments et des substances chimiques)</term>
<term>Régulation négative (génétique)</term>
<term>Régulation positive (effets des médicaments et des substances chimiques)</term>
<term>Régulation positive (génétique)</term>
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<term>Souris de lignée BALB C (MeSH)</term>
<term>Stress oxydatif (MeSH)</term>
<term>Séquence nucléotidique (MeSH)</term>
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<term>Virulence (effets des médicaments et des substances chimiques)</term>
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<div type="abstract" xml:lang="en">This study shows that the expression of yjcC, an in vivo expression (IVE) gene, and the stress response regulatory genes soxR, soxS, and rpoS are paraquat inducible in Klebsiella pneumoniae CG43. The deletion of rpoS or soxRS decreased yjcC expression, implying an RpoS- or SoxRS-dependent control. After paraquat or H2O2 treatment, the deletion of yjcC reduced bacterial survival. These effects could be complemented by introducing the ΔyjcC mutant with the YjcC-expression plasmid pJR1. The recombinant protein containing only the YjcC-EAL domain exhibited phosphodiesterase (PDE) activity; overexpression of yjcC has lower levels of cyclic di-GMP. The yjcC deletion mutant also exhibited increased reactive oxygen species (ROS) formation, oxidation damage, and oxidative stress scavenging activity. In addition, the yjcC deletion reduced capsular polysaccharide production in the bacteria, but increased the LD50 in mice, biofilm formation, and type 3 fimbriae major pilin MrkA production. Finally, a comparative transcriptome analysis showed 34 upregulated and 29 downregulated genes with the increased production of YjcC. The activated gene products include glutaredoxin I, thioredoxin, heat shock proteins, chaperone, and MrkHI, and proteins for energy metabolism (transporters, cell surface structure, and transcriptional regulation). In conclusion, the results of this study suggest that YjcC positively regulates the oxidative stress response and mouse virulence but negatively affects the biofilm formation and type 3 fimbriae expression by altering the c-di-GMP levels after receiving oxidative stress signaling inputs. </div>
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<AbstractText>This study shows that the expression of yjcC, an in vivo expression (IVE) gene, and the stress response regulatory genes soxR, soxS, and rpoS are paraquat inducible in Klebsiella pneumoniae CG43. The deletion of rpoS or soxRS decreased yjcC expression, implying an RpoS- or SoxRS-dependent control. After paraquat or H2O2 treatment, the deletion of yjcC reduced bacterial survival. These effects could be complemented by introducing the ΔyjcC mutant with the YjcC-expression plasmid pJR1. The recombinant protein containing only the YjcC-EAL domain exhibited phosphodiesterase (PDE) activity; overexpression of yjcC has lower levels of cyclic di-GMP. The yjcC deletion mutant also exhibited increased reactive oxygen species (ROS) formation, oxidation damage, and oxidative stress scavenging activity. In addition, the yjcC deletion reduced capsular polysaccharide production in the bacteria, but increased the LD50 in mice, biofilm formation, and type 3 fimbriae major pilin MrkA production. Finally, a comparative transcriptome analysis showed 34 upregulated and 29 downregulated genes with the increased production of YjcC. The activated gene products include glutaredoxin I, thioredoxin, heat shock proteins, chaperone, and MrkHI, and proteins for energy metabolism (transporters, cell surface structure, and transcriptional regulation). In conclusion, the results of this study suggest that YjcC positively regulates the oxidative stress response and mouse virulence but negatively affects the biofilm formation and type 3 fimbriae expression by altering the c-di-GMP levels after receiving oxidative stress signaling inputs. </AbstractText>
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