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Probing transport of fosfomycin through substrate specific OprO and OprP from Pseudomonas aeruginosa.

Abstract：

:Increasing antimicrobial drug resistance is a global threat especially with respect to Gram-negative bacteria. The low permeability of the bacterial outer cell wall has been identified as an important bottleneck that prevents a sufficient antibacterial effect to be achieved at low doses of the antibiotics. In particular, the outer membrane permeability for negatively charged molecules of the clinical important ESKAPE bacterium Pseudomonas aeruginosa is determined by the low conductance porins OprO and OprP Here we show that the alternative phosphonic-acid antibiotic fosfomycin is highly permeable through the OprO and OprP channels. For this, we applied an electrophysiological zero-current assay using concentration gradients of fosfomycin under tri-ionic conditions to quantify flux of fosfomycin through OprO and OprP. Our analyzes show that OprO, and to a lesser degree OprP, have unexpected very high permeability to fosfomycin, so the antibiotic should be a potentially excellent alternative choice for the control of Pseudomonas aeruginosa infections.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Citak F,Ghai I,Rosenkötter F,Benier L,Winterhalter M,Wagner R

doi

10.1016/j.bbrc.2017.11.188

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

1454-1460

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(17)32365-3

journal_volume

495

pub_type

杂志文章

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