Airway "Resistotypes" and Clinical Outcomes in Bronchiectasis.

Mac Aogáin, M; Ivan, FX; Jaggi, TK; Richardson, H; Shoemark, A; Narayana, JK; Dicker, AJ; Koh, MS; Lee, KCH; Thun How, O; Poh, ME; Chin, KK; Hou, ALY; Ser Hon, P; Low, TB; Abisheganaden, JA; Dimakou, K; Digalaki, A; Kosti, C; Gkousiou, A; Hansbro, PM; Blasi, F; Aliberti, S; Chalmers, JD; Chotirmall, SH

Airway "Resistotypes" and Clinical Outcomes in Bronchiectasis.

Mac Aogáin, M Ivan, FX Jaggi, TK Richardson, H Shoemark, A Narayana, JK Dicker, AJ Koh, MS Lee, KCH Thun How, O Poh, ME Chin, KK Hou, ALY Ser Hon, P Low, TB Abisheganaden, JA Dimakou, K Digalaki, A Kosti, C Gkousiou, A Hansbro, PM Blasi, F Aliberti, S Chalmers, JD Chotirmall, SH

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Publisher:: AMER THORACIC SOC
Publication Type:: Journal Article
Citation:: Am J Respir Crit Care Med, 2024, 210, (1), pp. 47-62
Issue Date:: 2024-07-01

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Field	Value	Language
dc.contributor.author	Mac Aogáin, M
dc.contributor.author	Ivan, FX
dc.contributor.author	Jaggi, TK
dc.contributor.author	Richardson, H
dc.contributor.author	Shoemark, A
dc.contributor.author	Narayana, JK
dc.contributor.author	Dicker, AJ
dc.contributor.author	Koh, MS
dc.contributor.author	Lee, KCH
dc.contributor.author	Thun How, O
dc.contributor.author	Poh, ME
dc.contributor.author	Chin, KK
dc.contributor.author	Hou, ALY
dc.contributor.author	Ser Hon, P
dc.contributor.author	Low, TB
dc.contributor.author	Abisheganaden, JA
dc.contributor.author	Dimakou, K
dc.contributor.author	Digalaki, A
dc.contributor.author	Kosti, C
dc.contributor.author	Gkousiou, A
dc.contributor.author	Hansbro, PM
dc.contributor.author	Blasi, F
dc.contributor.author	Aliberti, S
dc.contributor.author	Chalmers, JD
dc.contributor.author	Chotirmall, SH
dc.date.accessioned	2025-01-02T04:03:28Z
dc.date.available	2025-01-02T04:03:28Z
dc.date.issued	2024-07-01
dc.identifier.citation	Am J Respir Crit Care Med, 2024, 210, (1), pp. 47-62
dc.identifier.issn	1073-449X
dc.identifier.issn	1535-4970
dc.identifier.uri	http://hdl.handle.net/10453/182806
dc.description.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.
dc.format	Print
dc.language	eng
dc.publisher	AMER THORACIC SOC
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation	http://purl.org/au-research/grants/nhmrc/2010287
dc.relation.ispartof	Am J Respir Crit Care Med
dc.relation.isbasedon	10.1164/rccm.202306-1059OC
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	11 Medical and Health Sciences
dc.subject.classification	Respiratory System
dc.subject.classification	3201 Cardiovascular medicine and haematology
dc.subject.classification	3202 Clinical sciences
dc.subject.mesh	Bronchiectasis
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Female
dc.subject.mesh	Middle Aged
dc.subject.mesh	Aged
dc.subject.mesh	Cross-Sectional Studies
dc.subject.mesh	Longitudinal Studies
dc.subject.mesh	Anti-Bacterial Agents
dc.subject.mesh	Prospective Studies
dc.subject.mesh	Microbiota
dc.subject.mesh	Pseudomonas aeruginosa
dc.subject.mesh	Sputum
dc.subject.mesh	Metagenomics
dc.subject.mesh	Adult
dc.subject.mesh	Pseudomonas Infections
dc.subject.mesh	Sputum
dc.subject.mesh	Humans
dc.subject.mesh	Pseudomonas aeruginosa
dc.subject.mesh	Pseudomonas Infections
dc.subject.mesh	Bronchiectasis
dc.subject.mesh	Anti-Bacterial Agents
dc.subject.mesh	Longitudinal Studies
dc.subject.mesh	Prospective Studies
dc.subject.mesh	Cross-Sectional Studies
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Metagenomics
dc.subject.mesh	Microbiota
dc.subject.mesh	Bronchiectasis
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Female
dc.subject.mesh	Middle Aged
dc.subject.mesh	Aged
dc.subject.mesh	Cross-Sectional Studies
dc.subject.mesh	Longitudinal Studies
dc.subject.mesh	Anti-Bacterial Agents
dc.subject.mesh	Prospective Studies
dc.subject.mesh	Microbiota
dc.subject.mesh	Pseudomonas aeruginosa
dc.subject.mesh	Sputum
dc.subject.mesh	Metagenomics
dc.subject.mesh	Adult
dc.subject.mesh	Pseudomonas Infections
dc.title	Airway "Resistotypes" and Clinical Outcomes in Bronchiectasis.
dc.type	Journal Article
utslib.citation.volume	210
utslib.location.activity	United States
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Australian Institute for Microbiology & Infection (AIMI)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Inflammation (CFI)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Australian Institute for Microbiology & Infection (AIMI)/Australian Institute for Microbiology & Infection (AIMI) Associate Members
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated	2025-01-02T04:03:25Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	210
utslib.citation.issue	1

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.

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http://hdl.handle.net/10453/182806