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Pathogenesis of Achromobacter xylosoxidans respiratory infections: colonization and persistence in vivo and differential gene expression in cystic fibrosis sputum

ABSTRACT: The goals of this study were to determine differential gene expression between Achromobacter xylosoxidans clinical isolate Ax 7 in a synthetic artificial sputum media compared to a rich media control (LB).

ORGANISM(S): Achromobacter xylosoxidans

PROVIDER: GSE235679 | GEO | 2023/12/14

REPOSITORIES: GEO

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Pathogenesis of <i>Achromobacter xylosoxidans</i> respiratory infections: colonization, persistence, and transcriptome profiling in synthetic cystic fibrosis sputum medium.

Project description:Cystic fibrosis (CF) is a genetic disease affecting epithelial ion transport, resulting in thickened mucus and impaired mucociliary clearance. Persons with CF (pwCF) experience life-long infections of the respiratory mucosa caused by a diverse array of opportunists, which are leading causes of morbidity and mortality. In recent years, there has been increased appreciation for the range and diversity of microbes causing CF-related respiratory infections. The introduction of new therapeutics and improved detection methodology has revealed CF-related opportunists such as Achromobacter xylosoxidans (Ax). Ax is a Gram-negative bacterial species which is widely distributed in environmental sources and has been increasingly observed in sputa and other samples from pwCF, typically in patients in later stages of CF disease. In this study, we characterized CF clinical isolates of Ax and tested colonization and persistence of Ax in respiratory infection using immortalized human CF respiratory epithelial cells and BALB/c mice. Genomic analyses of clinical Ax isolates showed homologs for factors including flagellar synthesis, antibiotic resistance, and toxin secretion systems. Ax isolates adhered to polarized cultures of CFBE41o- human immortalized CF bronchial epithelial cells and caused significant cytotoxicity and depolarization of cell layers. Ax colonized and persisted in mouse lungs for up to 72 h post infection, with inflammatory consequences that include increased neutrophil influx in the lung, lung damage, cytokine production, and mortality. We also identified genes that are differentially expressed in synthetic CF sputum media. Based on these results, we conclude that Ax is an opportunistic pathogen of significance in CF.

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Stenotrophomonas maltophilia differential gene expression in synthetic cystic fibrosis sputum identifies shared and cystic fibrosis strain-specific expression responses to the sputum environment

Project description:We characterized the transcriptional responses of three S. maltophilia strains during exposure to synthetic CF sputum media (SCFM2) to gain insight into how this organism interacts with the host in the CF lung. These efforts led to the identification of 881 transcripts differentially expressed by all three strains, many of which reflect different metabolic pathways used by S. maltophilia in sputum, and altered stress responses. The latter correlated with increased resistance to peroxide exposure after pre-growth in SCFM2. We also compared the SCFM2 transcriptomes of two S. maltophilia CF isolates with the SCFM2 transcriptome of the acute infection model strain, S. maltophilia K279A, allowing us to identify CF isolate-specific signatures in differential gene expression that may be suggestive of adaptation to the CF lung. Each strain also possessed genes not shared by the other two and here we show that expression of some of the accessory genes in each strain are changed in response to SCFM2. Collectively, this work details the response of S. maltophilia to the CF lung environment, identifying potential survival strategies and metabolic pathways used by S. maltophilia during infections.

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Pathogenesis of Achromobacter xylosoxidans respiratory infections: colonization and persistence in vivo and differential gene expression in cystic fibrosis sputum

Project description:Pathogenesis of Achromobacter xylosoxidans respiratory infections: colonization and persistence in vivo and differential gene expression in cystic fibrosis sputum

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