Carbapenem-resistance oprD mutations reshape Pseudomonas aeruginosa host-pathogen interactions during infection.
| Title: | Carbapenem-resistance oprD mutations reshape Pseudomonas aeruginosa host-pathogen interactions during infection. |
|---|---|
| Authors: | Laborda P; Department of Clinical Microbiology 9301, Rigshospitalet, Copenhagen, Denmark. palama@dtu.dk.; Colque CA; Department of Clinical Microbiology 9301, Rigshospitalet, Copenhagen, Denmark.; La Rosa R; Department of Clinical Microbiology 9301, Rigshospitalet, Copenhagen, Denmark.; Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.; Molin S; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.; Johansen HK; Department of Clinical Microbiology 9301, Rigshospitalet, Copenhagen, Denmark.; Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. |
| Source: | Nature communications [Nat Commun] 2026 Apr 10. Date of Electronic Publication: 2026 Apr 10. |
| Publication Model: | Ahead of Print |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| Abstract: | Antibiotic resistance is a major global health threat. While its role in reducing drug susceptibility is well established, the broader consequences of resistance mutations on bacterial physiology and phenotype during infection remain poorly understood. Carbapenem-resistant Pseudomonas aeruginosa is considered among the highest-priority bacterial threats, with resistance commonly driven by loss-of-function mutations in the carbapenem uptake porin OprD. Here we show that such mutations can arise in clinical isolates even without prior carbapenem treatment, suggesting that their biological impact during infection is not limited to antibiotic resistance. Consistent with this, we found that oprD mutants exhibit enhanced early attachment to and translocation across airway epithelial barriers in an in vitro human infection model, an effect observed across strains with distinct clinical genomic backgrounds and infection dynamics. Our findings indicate that loss of OprD alters the bacterial outer membrane charge and reduces mucus entrapment, thereby facilitating epithelial barrier colonization. Overall, these results illustrate how antibiotic resistance mutations can directly shape infection dynamics, extending their impact well beyond antimicrobial susceptibility.; (© 2026. The Author(s).) |
| Competing Interests: | Competing interests: The authors declare no competing interests. |
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| Entry Date(s): | Date Created: 20260410 Latest Revision: 20260410 |
| Update Code: | 20260411 |
| DOI: | 10.1038/s41467-026-71782-5 |
| PMID: | 41963355 |
| Database: | MEDLINE |
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