Mac Aogain, Micheal and Ivan, Fransiskus Xaverius and Jaggi, Tavleen Kaur and Richardson, Hollian and Shoemark, Amelia and Narayana, Jayanth Kumar and Dicker, Alison J. and Koh, Mariko Siyue and Lee, Ken Cheah Hooi and How, Ong Thun and Poh, Mau Ern and Chin, Ka Kiat and Hou, Albert Lim Yick and Hon, Puah Ser and Low, Teck Boon and Abisheganaden, John Arputhan and Dimakou, Katerina and Digalaki, Antonia and Kosti, Chrysavgi and Gkousiou, Anna and Hansbro, Philip M. and Blasi, Francesco and Aliberti, Stefano and Chalmers, James D. and Chotirmall, Sanjay H. (2024) Airway ``Resistotypes'' and Clinical Outcomes in Bronchiectasis. American Journal of Respiratory and Critical Care Medicine, 210 (1, SI). pp. 47-62. ISSN 1073-449X, DOI https://doi.org/10.1164/rccm.202306-1059OC.
Full text not available from this repository.Abstract
Rationale: Chronic infection and inflammation shapes the airway microbiome in bronchiectasis. Utilizing whole-genome shotgun metagenomics to analyze the airway resistome provides insight into interplay between microbes, resistance genes, and clinical outcomes. Objectives: To apply whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis to highlight a diverse pool of antimicrobial resistance genes: the ``resistome,'' the clinical significance of which remains unclear. Methods: Individuals with bronchiectasis were prospectively recruited into cross-sectional and longitudinal cohorts (n = 280), including the international multicenter cross-sectional Cohort of Asian and Matched European Bronchiectasis 2 (CAMEB 2) study (n = 251) and two independent cohorts, one describing patients experiencing acute exacerbation and a further cohort of patients undergoing Pseudomonas aeruginosa eradication treatment. Sputum was subjected to metagenomic sequencing, and the bronchiectasis resistome was evaluated in association with clinical outcomes and underlying host microbiomes. Measurements and Main Results: The bronchiectasis resistome features a unique resistance gene profile and increased counts of aminoglycoside, bicyclomycin, phenicol, triclosan, and multidrug resistance genes. Longitudinally, it exhibits within-patient stability over time and during exacerbations despite between-patient heterogeneity. Proportional differences in baseline resistome profiles, including increased macrolide and multidrug resistance genes, associate with shorter intervals to the next exacerbation, whereas distinct resistome archetypes associate with frequent exacerbations, poorer lung function, geographic origin, and the host microbiome. Unsupervised analysis of resistome profiles identified two clinically relevant ``resistotypes,'' RT1 and RT2, the latter characterized by poor clinical outcomes, increased multidrug resistance, and P. aeruginosa. Successful targeted eradication in P. aeruginosa-colonized individuals mediated reversion from RT2 to RT1, a more clinically favorable resistome profile demonstrating reduced resistance gene diversity. Conclusions: The bronchiectasis resistome associates with clinical outcomes, geographic origin, and the underlying host microbiome. Bronchiectasis resistotypes link to clinical disease and are modifiable through targeted antimicrobial therapy.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | bronchiectasis; microbiome; metagenomics; resistome; resistotype |
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine > Medicine Department |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 24 Mar 2025 08:30 |
| Last Modified: | 24 Mar 2025 08:30 |
| URI: | http://eprints.um.edu.my/id/eprint/46854 |
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