Fosfomycin Uptake in Escherichia coli Is Mediated by the Outer-Membrane Porins OmpF, OmpC, and LamB,ACS Infectious Diseases

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Fosfomycin Uptake in Escherichia coli Is Mediated by the Outer-Membrane Porins OmpF, OmpC, and LamB
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2023-12-17 , DOI: 10.1021/acsinfecdis.3c00367
Martina Bianchi ₁ , Mathias Winterhalter ₂ , Theresa Anisja Harbig ₃ , Daniel Hörömpöli ₄ , Ishan Ghai ₂ , Kay Nieselt _{3,

5} , Heike Brötz-Oesterhelt _{4,

5} , Christoph Mayer _{1,

5} , Marina Borisova-Mayer _{1,

5}

Affiliation

The antibiotic fosfomycin (FOS) is widely recognized for the treatment of lower urinary tract infections with Escherichia coli 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 E. coli, its outer-membrane (OM) transport remains insufficiently understood. While evaluating minimal inhibitory concentrations in OM porin-deficient mutants, we observed that the E. coli ΔompFΔompC 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 E. coli.

中文翻译：

大肠埃希菌对磷霉素的摄取由外膜孔蛋白 OmpF、OmpC 和 LamB 介导

抗生素磷霉素（FOS）被广泛认为用于治疗大肠杆菌下尿路感染，最近作为对抗多重耐药细菌的治疗选择越来越重要。然而，对 FOS 的耐药性通常是通过突变减少其摄取而产生的。尽管 FOS 的内膜转运已在大肠杆菌中得到广泛研究，但其外膜（OM）转运仍未得到充分了解。在评估 OM 孔蛋白缺陷突变体中的最小抑制浓度时，我们观察到大肠杆菌 ΔompFΔompC 菌株对 FOS 的抗性是野生型和相应单个突变体的四倍。持续监测 FOS 诱导的孔蛋白缺陷菌株裂解还强调了 LamB 的重要性。通过电生理学和转录分析证实了 OmpF 、 OmpC 和 LamB 与 FOS 摄取的相关性。我们的研究首次深入探讨了 FOS 在大肠杆菌中通过 OM 的运输。

更新日期：2023-12-17

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