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Outer membrane permeability: Antimicrobials and diverse nutrients bypass porins in Pseudomonas aeruginosa

Ude, Johanna and Tripathi, Vishwachi and Buyck, Julien M. and Söderholm, Sandra and Cunrath, Olivier and Fanous, Joseph and Claudi, Beatrice and Egli, Adrian and Schleberger, Christian and Hiller, Sebastian and Bumann, Dirk. (2021) Outer membrane permeability: Antimicrobials and diverse nutrients bypass porins in Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences of the United States of America, 118 (31). e2107644118.

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Abstract

Gram-negative bacterial pathogens have an outer membrane that restricts entry of molecules into the cell. Water-filled protein channels in the outer membrane, so-called porins, facilitate nutrient uptake and are thought to enable antibiotic entry. Here, we determined the role of porins in a major pathogen,; Pseudomonas aeruginosa; , by constructing a strain lacking all 40 identifiable porins and 15 strains carrying only a single unique type of porin and characterizing these strains with NMR metabolomics and antimicrobial susceptibility assays. In contrast to common assumptions, all porins were dispensable for; Pseudomonas; growth in rich medium and consumption of diverse hydrophilic nutrients. However, preferred nutrients with two or more carboxylate groups such as succinate and citrate permeated poorly in the absence of porins. Porins provided efficient translocation pathways for these nutrients with broad and overlapping substrate selectivity while efficiently excluding all tested antibiotics except carbapenems, which partially entered through OprD. Porin-independent permeation of antibiotics through the outer-membrane lipid bilayer was hampered by carboxylate groups, consistent with our nutrient data. Together, these results challenge common assumptions about the role of porins by demonstrating porin-independent permeation of the outer-membrane lipid bilayer as a major pathway for nutrient and drug entry into the bacterial cell.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Hiller)
UniBasel Contributors:Hiller, Sebastian
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
ISSN:0027-8424
e-ISSN:1091-6490
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
edoc DOI:
Last Modified:08 Mar 2022 08:26
Deposited On:03 Mar 2022 12:01

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