Opis

• Tytuł:
  CRISPRi screen identifies FprB as a synergistic target for gallium therapy in Pseudomonas aeruginosa
• Twórca:
  Zhang, Yu;
  Zhang, Tingting;
  Xiao, Xue;
  Wang, Yejun;
  Kawalek, Adam;
  Ou, Jinzhao;
  Ren, Anmin;
  Sun, Wenhao;
  de Bakker, Vincent;
  Liu, Yujie;
  Li, Yuelong;
  Yang, Liang;
  Jia, Ning;
  Veening, Jan Willem;
  Liu, Xue
• Opis:
  With the rise of antibiotic-resistant bacteria, non-antibiotic therapies like gallium gain increasing attention. Intravenous gallium nitrate is under Phase II clinical trials to treat chronic Pseudomonas aeruginosa infections in cystic fibrosis patients. However, its clinical efficacy is constrained by the achievable peak concentration in human tissue. To address this limitation, we apply a genome-wide CRISPR interference approach (CRISPRi-seq) to identify potential synergistic targets with gallium. We classify the essential genes by response time and growth reduction, pinpointing the most vulnerable therapeutic targets in this species. In addition, we identify a highly conserved gene, fprB, encoding a ferredoxin-NADP⁺ reductase, whose deletion sensitizes P. aeruginosa to gallium, lowering its MIC by 32-fold and shifting mode of action from bacteriostatic to bactericidal. Further investigation reveals that FprB plays a critical role in modulating oxidative stress induced by gallium, via control of iron homeostasis and reactive oxygen species accumulation. Deleting fprB enhances gallium’s efficacy against biofilm formation and improves outcomes in a murine lung infection model of P. aeruginosa, suggesting FprB is a promising drug target in combination with gallium. Overall, our data show CRISPRi-seq as a powerful tool for systematic genetic analysis of P. aeruginosa, advancing the identification of novel therapeutic targets.
• Dostępność obiektu:
  Dostęp otwarty
• Data:
  2025.07.01
• Typ:
  Article;
  PeerReviewed
• Język:
  angielski
• Format:
  application/pdf
• Wydawca:
  Nature
• Relacja: http://eprints.ibb.waw.pl/2569 ;https://www.nature.com/articles/s41467-025-61208-z ;https://doi.org/10.1038/s41467-025-61208-z
• Temat i słowa kluczowe:
  QH301 Biology;
  QH426 Genetics;
  QR Microbiology
• Identyfikator: http://eprints.ibb.waw.pl/2569/1/s41467-025-61208-z.pdf ;
  Zhang, Yu and Zhang, Tingting and Xiao, Xue and Wang, Yejun and Kawalek, Adam and Ou, Jinzhao and Ren, Anmin and Sun, Wenhao and de Bakker, Vincent and Liu, Yujie and Li, Yuelong and Yang, Liang and Jia, Ning and Veening, Jan Willem and Liu, Xue (2025) CRISPRi screen identifies FprB as a synergistic target for gallium therapy in Pseudomonas aeruginosa. Nature Communications, 16 (5870). ISSN 2041-1723
• Dostawca danych:
  Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk
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