期刊
SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-022-14635-7
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资金
- Italian Ministry of Education, University and Research (MIUR) [20177J5Y3P, 202089LLEH]
Pseudomonas aeruginosa has two functional DksA paralogs, with DksA1 constitutively expressed and containing a zinc-finger motif, while DksA2 is only expressed under zinc starvation conditions. Both DksA1 and DksA2 play a role in the tolerance of P. aeruginosa to H2O2-induced oxidative stress, with DksA1 stimulating virulence factor production and being necessary for full pathogenicity in vivo. Complementation with either dksA1 or dksA2 genes restores wild type phenotypes, indicating their mutual contribution to P. aeruginosa virulence.
In Gram-negative pathogens, the stringent response regulator DksA controls the expression of hundreds of genes, including virulence-related genes. Interestingly, Pseudomonas aeruginosa has two functional DksA paralogs: DksA1 is constitutively expressed and has a zinc-finger motif, while DksA2 is expressed only under zinc starvation conditions and does not contain zinc. DksA1 stimulates the production of virulence factors in vitro and is required for full pathogenicity in vivo. DksA2 can replace these DksA1 functions. Here, the role of dksA paralogs in P. aeruginosa tolerance to H2O2-induced oxidative stress has been investigated. The P. aeruginosa dksA1 dksA2 mutant showed impaired H2O2 tolerance in planktonic and biofilm-growing cultures and increased susceptibility to macrophages-mediated killing compared to the wild type. Complementation with either dksA1 or dksA2 genes restored the wild type phenotypes. The DksA-dependent tolerance to oxidative stress involves, at least in part, the positive transcriptional control of both katA and katE catalase-encoding genes. These data support the hypothesis that DksA1 and DksA2 are eco-paralogs with indistinguishable function but optimal activity under different environmental conditions, and highlight their mutual contribution to P. aeruginosa virulence.
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