Human airway model reveals host-pathogen co-infection dynamics of Staphylococcus aureus and Pseudomonas aeruginosa
Abstract
Polymicrobial airway infections, particularly those involving Staphylococcus aureus and Pseudomonas aeruginosa, are a hallmark of severe chronic respiratory diseases such as those in people with cystic fibrosis (pwCF). Yet, the mechanisms enabling their co-existence remain poorly understood. Using a human air-liquid interface (ALI) airway model, we dissected host-pathogen and interspecies dynamics during mono- and co-infections with clinically relevant bacterial pathogens. We found that S. aureus strains exhibited distinct colonization patterns and virulence profiles, with the deletion of the agr quorum sensing locus leading to attenuated epithelial disruption. Additionally, the H1 component of P. aeruginosa’s type VI secretion system was critical for competitive exclusion of S. aureus, its deletion allowing for occasional co-localization of both species. Importantly, the order of co-infection strongly influenced pathogen dominance, with prior colonization of ALI models with S. aureus enabled coexistence with P. aeruginosa, thereby mimicking clinical observations in pwCF. Our results reveal that strain-specific traits and secretion systems influence microbial competition and persistence in the airway and underscore the importance of physiologically relevant models for studying chronic infections. Moreover, they provide the foundation for exploring therapeutic strategies for polymicrobial infections that account for the colonization sequence and microbial evolution for treatment design.
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BibTeX
@article{madsen2026human,
title = {{Human airway model reveals host-pathogen co-infection dynamics of Staphylococcus aureus and Pseudomonas aeruginosa}},
author = {Katrine Madsen and Signe Lolle and Martin Saxtorph Bojer and Hanne Ingmer and Helle Krogh Johansen and Søren Molin and Ruggero La Rosa},
journal = {ISME Communications},
year = {2026},
month = oct,
doi = {10.1093/ismeco/ycag284},
url = {https://doi.org/10.1093/ismeco/ycag284},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Human airway model reveals host-pathogen co-infection dynamics of Staphylococcus aureus and Pseudomonas aeruginosa
AU - Katrine Madsen
AU - Signe Lolle
AU - Martin Saxtorph Bojer
AU - Hanne Ingmer
AU - Helle Krogh Johansen
AU - Søren Molin
AU - Ruggero La Rosa
PY - 2026
DA - 2026/10/06
JO - ISME Communications
DO - 10.1093/ismeco/ycag284
UR - https://doi.org/10.1093/ismeco/ycag284
AB - Polymicrobial airway infections, particularly those involving Staphylococcus aureus and Pseudomonas aeruginosa, are a hallmark of severe chronic respiratory diseases such as those in people with cystic fibrosis (pwCF). Yet, the mechanisms enabling their co-existence remain poorly understood. Using a human air-liquid interface (ALI) airway model, we dissected host-pathogen and interspecies dynamics during mono- and co-infections with clinically relevant bacterial pathogens. We found that S. aureus strains exhibited distinct colonization patterns and virulence profiles, with the deletion of the agr quorum sensing locus leading to attenuated epithelial disruption. Additionally, the H1 component of P. aeruginosa’s type VI secretion system was critical for competitive exclusion of S. aureus, its deletion allowing for occasional co-localization of both species. Importantly, the order of co-infection strongly influenced pathogen dominance, with prior colonization of ALI models with S. aureus enabled coexistence with P. aeruginosa, thereby mimicking clinical observations in pwCF. Our results reveal that strain-specific traits and secretion systems influence microbial competition and persistence in the airway and underscore the importance of physiologically relevant models for studying chronic infections. Moreover, they provide the foundation for exploring therapeutic strategies for polymicrobial infections that account for the colonization sequence and microbial evolution for treatment design.
SN - 2730-6151
ER -