Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients
Open accessAbstract
Current theories of CF pathogenesis predict different predisposing "local environmental" conditions and sites of bacterial infection within CF airways.Here we show that, in CF patients with established lung disease, Psuedomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens.In vitro studies revealed that CF-specific increases in epithelial O 2 consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection.Motile P. aeruginosa deposited on CF airway surfaces penetrated into hypoxic mucus zones and responded to this environment with increased alginate production.With P. aeruginosa growth in oxygen restricted environments, local hypoxia was exacerbated and frank anaerobiosis, as detected in vivo, resulted.These studies indicate that novel therapies for CF include removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa adapted to anaerobic environments.
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In acute illness, the normally nutrient-poor alveolus is flooded with nutrient-rich oedema, oxygen and temperature gradients are established, and host stress signalling molecules selectively promote the growth of potential pathogens.
“The normally nutrient-poor environment of the alveolus is flooded with nutrient-rich oedema,55 pockets of oxygen and heterogeneous temperature gradients are established,48,49 and the signalling molecules of the host stress response selectively promote the growth of potential pathogens.”
From The microbiome and critical illness (2016) · cites this paper as [48]
The virulence of pathogens familiar in intensive care is promoted by conditions of nutrient scarcity, competition from neighbouring community members, disruption of stabilising commensal relationships, and exposure to the mediators of the host stress response.
“The virulence of pathogens familiar in intensive care is promoted by conditions of nutrient scarcity, competition from neighbouring community members, disruption of stabilising commensal relationships,20 and exposure to the mediators of the host stress response”
From The microbiome and critical illness (2016) · cites this paper as [48]
The influx of oedema into alveoli creates steep oxygen gradients, which shape bacterial community structure.
“The influx of oedema creates steep oxygen gradients, which shape bacterial community structure.”
From The microbiome and critical illness (2016) · cites this paper as [48]
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- Authors
- Worlitzsch, D., Tarran, R., Ulrich, M., Schwab, U., Cekici, A., Meyer, K. C., Birrer, P., Bellon, G., Berger, J., Weiss, T., Botzenhart, K., Yankaskas, J. R., Randell, S., Boucher, R. C., & Döring, G.
- Affiliations
- University of Tübingen (DE)
- University of North Carolina at Chapel Hill (US)
- University of Wisconsin–Madison (US)
- University of Bern (CH)
- Hôpital Lyon Sud (FR)
- Max Planck Institute for Developmental Biology (DE)
- Corresponding author
- Boucher, Richard C.
- Venue
- Journal of Clinical Investigation
- Published
- 2002-02-01
- Volume
- 109
- Issue
- 3
- Pages
- 317-325
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W4252523298
- Cited by
- 932
- References
- 34
- Citations by year
- 2026: 20 · 2025: 28 · 2024: 32 · 2023: 35 · 2022: 39 · 2021: 36 · 2020: 44 · 2019: 45 · 2018: 46 · 2017: 45 · 2016: 51 · 2015: 40 · 2014: 58 · 2013: 51 · 2012: 31
- FWCI
- 25.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Infections and bacterial resistance
- Keywords
- cystic fibrosis, Pseudomonas aeruginosa, airway infection, hypoxia, airway surface liquid, alginate production, anaerobic conditions
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