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Title: Substrate Specificity within a Family of Outer Membrane Carboxylate Channels

Abstract

Many Gram-negative bacteria, including human pathogens such as Pseudomonas aeruginosa, do not have large-channel porins. This results in an outer membrane (OM) that is highly impermeable to small polar molecules, making the bacteria intrinsically resistant towards many antibiotics. In such microorganisms, the majority of small molecules are taken up by members of the OprD outer membrane protein family. Here we show that OprD channels require a carboxyl group in the substrate for efficient transport, and based on this we have renamed the family Occ, for outer membrane carboxylate channels. We further show that Occ channels can be divided into two subfamilies, based on their very different substrate specificities. Our results rationalize how certain bacteria can efficiently take up a variety of substrates under nutrient-poor conditions without compromising membrane permeability. In addition, they explain how channel inactivation in response to antibiotics can cause resistance but does not lead to decreased fitness.

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1069493
Report Number(s):
BNL-100065-2013-JA
Journal ID: ISSN 1545-7885
DOE Contract Number:
AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: PLoS biology (Online); Journal Volume: 10; Journal Issue: 1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Eren, Elif, Vijayaraghavan, Jagamya, Liu, Jiaming, Cheneke, Belete R., Touw, Debra S., Lepore, Bryan W., Indic, Mridhu, Movileanu, Liviu, van den Berg, Bert, and Dutzler, Raimund. Substrate Specificity within a Family of Outer Membrane Carboxylate Channels. United States: N. p., 2012. Web. doi:10.1371/journal.pbio.1001242.
Eren, Elif, Vijayaraghavan, Jagamya, Liu, Jiaming, Cheneke, Belete R., Touw, Debra S., Lepore, Bryan W., Indic, Mridhu, Movileanu, Liviu, van den Berg, Bert, & Dutzler, Raimund. Substrate Specificity within a Family of Outer Membrane Carboxylate Channels. United States. doi:10.1371/journal.pbio.1001242.
Eren, Elif, Vijayaraghavan, Jagamya, Liu, Jiaming, Cheneke, Belete R., Touw, Debra S., Lepore, Bryan W., Indic, Mridhu, Movileanu, Liviu, van den Berg, Bert, and Dutzler, Raimund. 2012. "Substrate Specificity within a Family of Outer Membrane Carboxylate Channels". United States. doi:10.1371/journal.pbio.1001242.
@article{osti_1069493,
title = {Substrate Specificity within a Family of Outer Membrane Carboxylate Channels},
author = {Eren, Elif and Vijayaraghavan, Jagamya and Liu, Jiaming and Cheneke, Belete R. and Touw, Debra S. and Lepore, Bryan W. and Indic, Mridhu and Movileanu, Liviu and van den Berg, Bert and Dutzler, Raimund},
abstractNote = {Many Gram-negative bacteria, including human pathogens such as Pseudomonas aeruginosa, do not have large-channel porins. This results in an outer membrane (OM) that is highly impermeable to small polar molecules, making the bacteria intrinsically resistant towards many antibiotics. In such microorganisms, the majority of small molecules are taken up by members of the OprD outer membrane protein family. Here we show that OprD channels require a carboxyl group in the substrate for efficient transport, and based on this we have renamed the family Occ, for outer membrane carboxylate channels. We further show that Occ channels can be divided into two subfamilies, based on their very different substrate specificities. Our results rationalize how certain bacteria can efficiently take up a variety of substrates under nutrient-poor conditions without compromising membrane permeability. In addition, they explain how channel inactivation in response to antibiotics can cause resistance but does not lead to decreased fitness.},
doi = {10.1371/journal.pbio.1001242},
journal = {PLoS biology (Online)},
number = 1,
volume = 10,
place = {United States},
year = 2012,
month = 1
}
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