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

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

PROVIDER: PRJNA986891 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25010253_1.fastq.gz	Fastqsanger.gz
	SRR25010253_2.fastq.gz	Fastqsanger.gz
	SRR25010254_1.fastq.gz	Fastqsanger.gz
	SRR25010254_2.fastq.gz	Fastqsanger.gz
	SRR25010255_1.fastq.gz	Fastqsanger.gz

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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: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).

2023-12-14 | GSE235679 | GEO

The Achromobacter xylosoxidans type VI secretion system 2 (T6SS): from clinical to molecular evidences of its 3 implication in cystic fibrosis

Project description:Bacteria of the genus Achromobacter are environmental germs, with an unknown reservoir, which can become opportunistic pathogens in immunocompromised patients, and be responsible for bacteremia, meningitis, pneumonia and peritonitis. Achromobacter xylosoxidans is an emerging pathogenic bacterium frequently isolated in the context of cystic fibrosis (CF). Recent studies show that A. xylosoxidans is involved in the degradation of the respiratory function of CF patients. The respiratory ecosystem of CF patients is colonized by bacterial species that constantly fight for space and access to nutrients. In particular, these bacteria use an antagonism system, a type VI secretion nanomachine (T6SS), which represents a virulence factor in many pathogenic bacteria. This study aimed to investigate the prevalence of the T6SS genes in Achromobacter xylosoxidans isolated in cystic fibrosis patient. We also evaluated clinical and molecular characteristics of T6SS-positive A. xylosoxidans strains. We have shown that A. xylosoxidans possesses a T6SS-encoded gene cluster and that some environmental and clinical isolates assemble a functional T6SS nanomachine. The A. xylosoxidans T6SS is used to target competitor bacteria, including other CF-specific pathogens. We gathered some evidences pointing toward a role of T6SS in CF-lung colonization: i, CF mimicking conditions trigger the activation of A. xylosoxidans T6SS; ii, we detected Hcp in the sputum of CF patient and iii, the T6SS helps internalization of A. xylosoxidans in lung epithelial cells. Our study highlights a new clinical determinant of the virulence of A. xylosoxidans as well as new diagnostic and therapeutic options in cystic fibrosis.

2024-02-01 | PXD031682 | Pride

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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