Fosmidomycin transport through the phosphate‐specific porins OprO and OprP of Pseudomonas aeruginosa
Please always quote using this URN: urn:nbn:de:bvb:20-opus-238905
- The Gram‐negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen, responsible for many hospital‐acquired infections. The bacterium is quite resistant toward many antibiotics, in particular because of the fine‐tuned permeability of its outer membrane (OM). General diffusion outer membrane pores are quite rare in this organism. Instead, its OM contains many substrate‐specific porins. Their expression is varying according to growth conditions and virulence. Phosphate limitations, as well as pathogenicity factors, result in theThe Gram‐negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen, responsible for many hospital‐acquired infections. The bacterium is quite resistant toward many antibiotics, in particular because of the fine‐tuned permeability of its outer membrane (OM). General diffusion outer membrane pores are quite rare in this organism. Instead, its OM contains many substrate‐specific porins. Their expression is varying according to growth conditions and virulence. Phosphate limitations, as well as pathogenicity factors, result in the induction of the two mono‐ and polyphosphate‐specific porins, OprP and OprO, respectively, together with an inner membrane uptake mechanism and a periplasmic binding protein. These outer membrane channels could serve as outer membrane pathways for the uptake of phosphonates. Among them are not only herbicides, but also potent antibiotics, such as fosfomycin and fosmidomycin. In this study, we investigated the interaction between OprP and OprO and fosmidomycin in detail. We could demonstrate that fosmidomycin is able to bind to the phosphate‐specific binding site inside the two porins. The inhibition of chloride conductance of OprP and OprO by fosmidomycin is considerably less than that of phosphate or diphosphate, but it can be measured in titration experiments of chloride conductance and also in single‐channel experiments. The results suggest that fosmidomycin transport across the OM of P. aeruginosa occurs through OprP and OprO. Our data with the ones already known in the literature show that phosphonic acid‐containing antibiotics are in general good candidates to treat the infections of P. aeruginosa at the very beginning through a favorable OM transport system.…
Author: | Claudio Piselli, Roland Benz |
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URN: | urn:nbn:de:bvb:20-opus-238905 |
Document Type: | Journal article |
Faculties: | Fakultät für Biologie / Rudolf-Virchow-Zentrum |
Language: | English |
Parent Title (English): | Molecular Microbiology |
Year of Completion: | 2021 |
Volume: | 116 |
Issue: | 1 |
First Page: | 97 |
Last Page: | 108 |
Source: | Molecular Microbiology 2021, 116(1):97-108. DOI: 10.1111/mmi.14693 |
DOI: | https://doi.org/10.1111/mmi.14693 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Tag: | OprO; OprP; fosmidomycin; lipid bilayer membrane; porin |
Release Date: | 2021/12/20 |
Licence (German): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |