De novo mutations mediate phenotypic switching in an opportunistic human lung pathogen.

Autor:	Poret AJ; Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology.; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology.; Department of Biological Engineering, Massachusetts Institute of Technology., Schaefers M; Department of Anesthesiology, Critical Care and Pain Medicine, Division of Critical Care Medicine, Boston Children's Hospital.; Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts., Merakou C; Department of Anesthesiology, Critical Care and Pain Medicine, Division of Critical Care Medicine, Boston Children's Hospital.; Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts., Mansour KE; Department of Anesthesiology, Critical Care and Pain Medicine, Division of Critical Care Medicine, Boston Children's Hospital., Lagoudas GK; Department of Biological Engineering, Massachusetts Institute of Technology.; Broad Institute of MIT and Harvard., Cross AR; Department of Pediatrics, Division of Pulmonary, Asthma, Cystic Fibrosis, and Sleep, Emory University School of Medicine., Goldberg JB; Department of Pediatrics, Division of Pulmonary, Asthma, Cystic Fibrosis, and Sleep, Emory University School of Medicine., Kishony R; Faculty of Biology and Faculty of Computer Science, Technion Israel., Uluer AZ; Department of Pediatrics, Division of Respiratory Diseases, Boston Children's Hospital.; Adult CF Program, Brigham and Women's Hospital.; Department of Pediatrics, Harvard Medical School., McAdam AJ; Department of Laboratory Medicine, Boston Children's Hospital.; Department of Pathology, Harvard Medical School., Blainey PC; Department of Biological Engineering, Massachusetts Institute of Technology.; Broad Institute of MIT and Harvard.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology., Vargas SO; Department of Pathology, Harvard Medical School.; Department of Pathology, Boston Children's Hospital., Lieberman TD; Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology.; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology.; Department of Anesthesiology, Critical Care and Pain Medicine, Division of Critical Care Medicine, Boston Children's Hospital., Priebe GP; Department of Anesthesiology, Critical Care and Pain Medicine, Division of Critical Care Medicine, Boston Children's Hospital.; Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts.; Broad Institute of MIT and Harvard.; Department of Pediatrics, Division of Infectious Diseases, Boston Children's Hospital.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 06. Date of Electronic Publication: 2024 Feb 06.
DOI:	10.1101/2024.02.06.579193
Abstrakt:	Bacteria evolving within human hosts encounter selective tradeoffs that render mutations adaptive in one context and deleterious in another. Here, we report that the cystic fibrosis-associated pathogen Burkholderia dolosa overcomes in-human selective tradeoffs by acquiring successive point mutations that alternate phenotypes. We sequenced the whole genomes of 931 respiratory isolates from two recently infected patients and an epidemiologically-linked, chronically-infected patient. These isolates are contextualized using 112 historical genomes from the same outbreak strain. Within both newly infected patients, diverse parallel mutations that disrupt O-antigen expression quickly arose, comprising 29% and 63% of their B. dolosa communities by 3 years. The selection for loss of O-antigen starkly contrasts with our previous observation of parallel O-antigen-restoring mutations after many years of chronic infection in the historical outbreak. Experimental characterization revealed that O-antigen loss increases uptake in immune cells while decreasing competitiveness in the mouse lung. We propose that the balance of these pressures, and thus whether O-antigen expression is advantageous, depends on tissue localization and infection duration. These results suggest that mutation-driven alternation during infection may be more frequent than appreciated and is underestimated without dense temporal sampling.
Databáze:	MEDLINE
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