Monothiol Glutaredoxin Is Essential for Oxidative Stress Protection and Virulence in Pseudomonas aeruginosa.
Kritsakorn SaninjukAdisak RomsangJintana Duang-NkernLampet WongsarojPanithi LeesukonJames M DubbsPaiboon VattanaviboonSkorn MongkolsukPublished in: Applied and environmental microbiology (2022)
Glutaredoxins (Grxs), ubiquitous redox enzymes belonging to the thioredoxin family, catalyze the reduction of thiol-disulfide exchange reactions in a glutathione-dependent manner. A Pseudomonas aeruginosa Δ grxD mutant exhibited hypersensitivity to oxidative stress-generating agents, such as paraquat (PQ) and cumene hydroperoxide (CHP). In vitro studies showed that P. aeruginosa GrxD acts as an electron donor for organic hydroperoxide resistance enzyme (Ohr) during CHP degradation. The ectopic expression of iron-sulfur cluster ([Fe-S]) carrier proteins, including ErpA, IscA, and NfuA, complements the function of GrxD in the Δ grxD mutant under PQ toxicity. Constitutively high expression of iscR , nfuA , tpx , and fprB was observed in the Δ grxD mutant. These results suggest that GrxD functions as a [Fe-S] cluster carrier protein involved in [Fe-S] cluster maturation. Moreover, the Δ grxD mutant demonstrates attenuated virulence in a Drosophila melanogaster host model. Altogether, the data shed light on the physiological role of GrxD in oxidative stress protection and virulence of the human pathogen, P. aeruginosa. IMPORTANCE Glutaredoxins (Grxs) are ubiquitous disulfide reductase enzymes. Monothiol Grxs, containing a CXXS motif, play an essential role in iron homeostasis and maturation of [Fe-S] cluster proteins in various organisms. We now establish that the human pathogen Pseudomonas aeruginosa GrxD is crucial for bacterial virulence, maturation of [Fe-S] clusters and facilitation of Ohr enzyme activity. GrxD contains a conserved signature monothiol motif (C 29 GFS), in which C29 is essential for its function in an oxidative stress protection. Our findings reveal the physiological roles of GrxD in oxidative stress protection and virulence of P. aeruginosa.
Keyphrases
- pseudomonas aeruginosa
- oxidative stress
- biofilm formation
- cystic fibrosis
- acinetobacter baumannii
- dna damage
- escherichia coli
- diabetic rats
- staphylococcus aureus
- endothelial cells
- induced apoptosis
- ischemia reperfusion injury
- poor prognosis
- antimicrobial resistance
- metal organic framework
- candida albicans
- wild type
- binding protein
- drosophila melanogaster
- aqueous solution
- heat shock
- transcription factor
- visible light
- big data
- gene expression
- genome wide
- iron deficiency
- deep learning
- protein protein
- gram negative
- pulmonary fibrosis