Pseudomonas aeruginosa lasR mutant fitness in microoxia is supported by an Anr-regulated oxygen-binding hemerythrin.

Autor: Clay ME; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755., Hammond JH; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755., Zhong F; Department of Chemistry, Dartmouth College, Hanover, NH 03755., Chen X; Department of Chemistry, Dartmouth College, Hanover, NH 03755., Kowalski CH; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755., Lee AJ; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104., Porter MS; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755., Hampton TH; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755., Greene CS; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104., Pletneva EV; Department of Chemistry, Dartmouth College, Hanover, NH 03755., Hogan DA; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755; deborah.a.hogan@dartmouth.edu.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Feb 11; Vol. 117 (6), pp. 3167-3173. Date of Electronic Publication: 2020 Jan 24.
DOI: 10.1073/pnas.1917576117
Abstrakt: Pseudomonas aeruginosa strains with loss-of-function mutations in the transcription factor LasR are frequently encountered in the clinic and the environment. Among the characteristics common to LasR-defective (LasR-) strains is increased activity of the transcription factor Anr, relative to their LasR+ counterparts, in low-oxygen conditions. One of the Anr-regulated genes found to be highly induced in LasR- strains was PA14_42860 ( PA1673 ), which we named mhr for microoxic hemerythrin. Purified P. aeruginosa Mhr protein contained the predicted di-iron center and bound molecular oxygen with an apparent K d of ∼1 µM. Both Anr and Mhr were necessary for fitness in lasR + and lasR mutant strains in colony biofilms grown in microoxic conditions, and the effects were more striking in the lasR mutant. Among genes in the Anr regulon, mhr was most closely coregulated with the Anr-controlled high-affinity cytochrome c oxidase genes. In the absence of high-affinity cytochrome c oxidases, deletion of mhr no longer caused a fitness disadvantage, suggesting that Mhr works in concert with microoxic respiration. We demonstrate that Anr and Mhr contribute to LasR- strain fitness even in biofilms grown in normoxic conditions. Furthermore, metabolomics data indicate that, in a lasR mutant, expression of Anr-regulated mhr leads to differences in metabolism in cells grown on lysogeny broth or artificial sputum medium. We propose that increased Anr activity leads to higher levels of the oxygen-binding protein Mhr, which confers an advantage to lasR mutants in microoxic conditions.
Competing Interests: The authors declare no competing interest.
Databáze: MEDLINE
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