Role of O-specific antigen expression in Pseudomonas aeruginosa pathogenicity
8 affiliations
- 1Department of Molecular Bacteriology, Helmholtz Centre for Infection Research (HZI)
- 2Institute of Molecular Bacteriology, TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School (MHH) and the HZI
- 3Cluster of Excellence RESIST (EXC 2155), Hannover Medical School
- 4Department of Clinical Microbiology, Copenhagen University Hospital—Rigshospitalet
- 5Institute of Preventive Veterinary Medicine, Sichuan Agricultural University
- 6Research Center of Avian Diseases, College of Veterinary Medicine, Sichuan Agricultural University
- 7Key Laboratory of Animal Disease and Human Health of Sichuan Province
- 8Central Facility for Microscopy, Helmholtz Centre for Infection Research
Abstract
Pseudomonas aeruginosa is a versatile, opportunistic pathogen, well-known for its adaptability to the challenging conditions encountered during infection of the human host. In chronic biofilm-associated infections, variations in motility and LPS structure are commonly observed adaptive traits. In this study, we identified differences in the expression of the O-specific antigen (OSA) biosynthetic cluster as a key driver of motility variation among a large number of clinical PA14 clade isolates. Despite retaining flagellar presence and function, OSA-deficient mutants exhibited increased hydrophobicity, which enhanced surface attachment and, in turn, reduced surface motility while promoting biofilm formation. The modified lipopolysaccharide structure with a lack of OSA also resulted in increased serum sensitivity, reduced phagocytic uptake, increased aminoglycoside resistance, and enhanced expression of the type III secretion system. These findings suggest that the commonly observed loss of OSA in P. aeruginosa isolates recovered from chronically infected cystic fibrosis lungs may be selectively advantageous. Importantly, we demonstrate that clinically relevant phenotypes influenced by the presence of OSA, such as motility and antibiotic resistance, become detectable only under test conditions that promote bacterial attachment. Similarly, the role of OSA expression in bacterial pathogenicity is conditional, with neither its presence nor its absence uniformly favoring infection. Together, our findings support a model in which OSA expression may be beneficial during early infection, whereas reduced OSA expression may promote traits associated with persistence at later stages.
IMPORTANCE: Loss of the O-specific antigens (OSA) in Pseudomonas aeruginosa isolates recovered from chronically infected cystic fibrosis lungs is a commonly observed phenotype that may confer a selective advantage to this opportunistic pathogen. In this study, we demonstrate that P. aeruginosa strains lacking OSA become more adhesive, limiting their motility but enhancing biofilm formation. Furthermore, OSA-deficient strains exhibit increased serum sensitivity, while they are phagocytosed less, express elevated type III secretion system genes, and show enhanced antibiotic resistance. Our findings suggest that altered OSA expression may contribute to stage-dependent infection phenotypes, where reduced OSA expression during later stages drives biofilm formation and antibiotic resistance, thereby enabling persistence.
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BibTeX
@article{hartmann2026role,
title = {{Role of O-specific antigen expression in Pseudomonas aeruginosa pathogenicity}},
author = {Oliver Hartmann and Matthias Preusse and Ann Kathrin Heroven and Sebastian Felgner and Melisa Gür and Adrian Kordes and Victor Wolff Bengtsen and Mohammad Roghanian and Xinxin Zhao and Mathias Müsken and Nicolas Oswaldo Gomez and Susanne Häussler},
journal = {mBio},
year = {2026},
month = oct,
doi = {10.1128/mbio.01551-26},
url = {https://journals.asm.org/doi/10.1128/mbio.01551-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Role of O-specific antigen expression in Pseudomonas aeruginosa pathogenicity
AU - Oliver Hartmann
AU - Matthias Preusse
AU - Ann Kathrin Heroven
AU - Sebastian Felgner
AU - Melisa Gür
AU - Adrian Kordes
AU - Victor Wolff Bengtsen
AU - Mohammad Roghanian
AU - Xinxin Zhao
AU - Mathias Müsken
AU - Nicolas Oswaldo Gomez
AU - Susanne Häussler
PY - 2026
DA - 2026/10/05
JO - mBio
DO - 10.1128/mbio.01551-26
UR - https://journals.asm.org/doi/10.1128/mbio.01551-26
AB - Pseudomonas aeruginosa is a versatile, opportunistic pathogen, well-known for its adaptability to the challenging conditions encountered during infection of the human host. In chronic biofilm-associated infections, variations in motility and LPS structure are commonly observed adaptive traits. In this study, we identified differences in the expression of the O-specific antigen (OSA) biosynthetic cluster as a key driver of motility variation among a large number of clinical PA14 clade isolates. Despite retaining flagellar presence and function, OSA-deficient mutants exhibited increased hydrophobicity, which enhanced surface attachment and, in turn, reduced surface motility while promoting biofilm formation. The modified lipopolysaccharide structure with a lack of OSA also resulted in increased serum sensitivity, reduced phagocytic uptake, increased aminoglycoside resistance, and enhanced expression of the type III secretion system. These findings suggest that the commonly observed loss of OSA in P. aeruginosa isolates recovered from chronically infected cystic fibrosis lungs may be selectively advantageous. Importantly, we demonstrate that clinically relevant phenotypes influenced by the presence of OSA, such as motility and antibiotic resistance, become detectable only under test conditions that promote bacterial attachment. Similarly, the role of OSA expression in bacterial pathogenicity is conditional, with neither its presence nor its absence uniformly favoring infection. Together, our findings support a model in which OSA expression may be beneficial during early infection, whereas reduced OSA expression may promote traits associated with persistence at later stages. IMPORTANCE: Loss of the O-specific antigens (OSA) in Pseudomonas aeruginosa isolates recovered from chronically infected cystic fibrosis lungs is a commonly observed phenotype that may confer a selective advantage to this opportunistic pathogen. In this study, we demonstrate that P. aeruginosa strains lacking OSA become more adhesive, limiting their motility but enhancing biofilm formation. Furthermore, OSA-deficient strains exhibit increased serum sensitivity, while they are phagocytosed less, express elevated type III secretion system genes, and show enhanced antibiotic resistance. Our findings suggest that altered OSA expression may contribute to stage-dependent infection phenotypes, where reduced OSA expression during later stages drives biofilm formation and antibiotic resistance, thereby enabling persistence.
SN - 2150-7511
ER -