The Pseudomonas aeruginosa sirB2 gene is a fitness determinant of anaerobic growth and its inactivation affects virulence and rugose small colony variants emergence.
| Title: | The Pseudomonas aeruginosa sirB2 gene is a fitness determinant of anaerobic growth and its inactivation affects virulence and rugose small colony variants emergence. |
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| Authors: | Baldelli V; Department of Biosciences, University of Milan, Milan, Italy.; Carrasco Aliaga SJ; Department of Biosciences, University of Milan, Milan, Italy.; Colque CA; Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.; Mazzola F; Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy.; Ravishankar S; Department of Biosciences, University of Milan, Milan, Italy.; Johansen HK; Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Denmark.; Molin S; Department of Clinical Medicine Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Raffaelli N; Department of Agricultural, Food and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy.; Paroni M; Department of Biosciences, University of Milan, Milan, Italy.; Landini P; Department of Biosciences, University of Milan, Milan, Italy.; Rossi E; Department of Biosciences, University of Milan, Milan, Italy. |
| Source: | Virulence [Virulence] 2026 Dec; Vol. 17 (1), pp. 2605800. Date of Electronic Publication: 2025 Dec 21. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101531386 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-5608 (Electronic) Linking ISSN: 21505594 NLM ISO Abbreviation: Virulence Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2015- : Philadelphia, PA : Taylor & Francis; Original Publication: Austin, Tex. : Landes Bioscience |
| MeSH Terms: | Pseudomonas aeruginosa*/genetics ; Pseudomonas aeruginosa*/pathogenicity ; Pseudomonas aeruginosa*/growth & development ; Pseudomonas aeruginosa*/metabolism ; Bacterial Proteins*/genetics ; Bacterial Proteins*/metabolism ; Genetic Fitness*; Virulence/genetics ; Biofilms/growth & development ; Pseudomonas Infections/microbiology ; Moths/microbiology ; Cystic Fibrosis/microbiology ; Cyclic GMP/analogs & derivatives ; Cyclic GMP/metabolism ; Animals ; Anaerobiosis ; Gene Expression Regulation, Bacterial ; Humans |
| Abstract: | Pseudomonas aeruginosa is the leading cause of death in cystic fibrosis (CF) patients, yet the genetic mechanisms driving its fitness in the host remain poorly defined. Previously collected transcriptomic data of clinical samples showed that expression of the gene PA14_RS04555 (sirB2) is stimulated in the CF lung environment. In this work, we show that sirB2 is regulated by the global transcriptional regulators Vfr and AmrZ. Loss of sirB2 markedly enhanced P. aeruginosa pathogenicity, increasing virulence in Galleria mellonella, and promoting bacterial translocation and biofilm formation in a differentiated airway epithelial infection model. Deletion of sirB2 triggered the emergence of biofilm-proficient rugose small colony variants (RSCVs), driven by elevated c-di-GMP and increased Pel polysaccharide production when cultures were grown in static conditions. The RSCV phenotype depends on suppressor mutations in the wsp operon, possibly as a response to redox imbalance caused by the lack of sirB2 under oxygen-limited conditions. Indeed, the sirB2 mutant exhibited impaired fitness during anaerobic respiration when nitrate was the sole electron acceptor, in a manner independent of the ubiquinone pool. Our findings show that sirB2 inactivation promotes RSCV emergence and identify sirB2 as a novel genetic determinant of metabolic fitness under host-relevant conditions, thereby underscoring the role of redox balance in chronic CF infections. |
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| Contributed Indexing: | Keywords: Pseudomonas aeruginosa; anaerobic respiration; biofilm; redox imbalance; rugose small colony variants; virulence |
| Substance Nomenclature: | 0 (Bacterial Proteins); H2D2X058MU (Cyclic GMP) |
| Entry Date(s): | Date Created: 20251217 Date Completed: 20251221 Latest Revision: 20251224 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12721095 |
| DOI: | 10.1080/21505594.2025.2605800 |
| PMID: | 41408422 |
| Database: | MEDLINE |
Journal Article