AI Article Synopsis
- Fosfomycin (FOS) is an important antibiotic for treating lower urinary tract infections and is increasingly used against multidrug-resistant bacteria.
- Resistance to FOS often arises from mutations that hinder its uptake, and previous research has mainly focused on its transport across the inner membrane.
- The study reveals that certain outer-membrane proteins, particularly OmpF, OmpC, and LamB, are crucial for FOS uptake, showing that a specific mutant strain is significantly more resistant compared to the wild type.
Article Abstract
The antibiotic fosfomycin (FOS) is widely recognized for the treatment of lower urinary tract infections with and has lately gained importance as a therapeutic option to combat multidrug-resistant bacteria. However, resistance to FOS frequently develops through mutations reducing its uptake. Although the inner-membrane transport of FOS has been extensively studied in , its outer-membrane (OM) transport remains insufficiently understood. While evaluating minimal inhibitory concentrations in OM porin-deficient mutants, we observed that the ΔΔ strain is four times more resistant to FOS than the wild type and the respective single mutants. Continuous monitoring of FOS-induced lysis of porin-deficient strains additionally highlighted the importance of LamB. The relevance of OmpF, OmpC, and LamB to FOS uptake was confirmed by electrophysiological and transcriptional analysis. Our study gives for the first time in-depth insight into the transport of FOS through the OM in .
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789261 | PMC |
| http://dx.doi.org/10.1021/acsinfecdis.3c00367 | DOI Listing |
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