Substrate specificity within a family of outer membrane carboxylate channels

Elif Eren, Jagamya Vijayaraghavan, Jiaming Liu, Belete R. Cheneke, Debra S. Touw, Bryan W. Lepore, Mridhu Indic, Liviu Movileanu, Bert van den Berg

Research output: Contribution to journalArticle

  • 46 Citations

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.

Original languageEnglish (US)
Article numbere1001242
JournalPLoS biology.
Volume10
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

Substrate Specificity
Ion Channels
Anti-Bacterial Agents
Bacteria
Membranes
substrate specificity
antibiotics
bacteria
Bronchiolo-Alveolar Adenocarcinoma
Substrates
Bufo arenarum
Porins
Gram-Negative Bacteria
Pseudomonas aeruginosa
Permeability
Membrane Proteins
Food
porins
outer membrane proteins
membrane permeability

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Eren, E., Vijayaraghavan, J., Liu, J., Cheneke, B. R., Touw, D. S., Lepore, B. W., ... van den Berg, B. (2012). Substrate specificity within a family of outer membrane carboxylate channels. PLoS biology., 10(1), [e1001242]. DOI: 10.1371/journal.pbio.1001242

Substrate specificity within a family of outer membrane carboxylate channels. / Eren, Elif; Vijayaraghavan, Jagamya; Liu, Jiaming; Cheneke, Belete R.; Touw, Debra S.; Lepore, Bryan W.; Indic, Mridhu; Movileanu, Liviu; van den Berg, Bert.

In: PLoS biology., Vol. 10, No. 1, e1001242, 01.2012.

Research output: Contribution to journalArticle

Eren, E, Vijayaraghavan, J, Liu, J, Cheneke, BR, Touw, DS, Lepore, BW, Indic, M, Movileanu, L & van den Berg, B 2012, 'Substrate specificity within a family of outer membrane carboxylate channels' PLoS biology., vol 10, no. 1, e1001242. DOI: 10.1371/journal.pbio.1001242
Eren E, Vijayaraghavan J, Liu J, Cheneke BR, Touw DS, Lepore BW et al. Substrate specificity within a family of outer membrane carboxylate channels. PLoS biology. 2012 Jan;10(1). e1001242. Available from, 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 / Substrate specificity within a family of outer membrane carboxylate channels.

In: PLoS biology., Vol. 10, No. 1, e1001242, 01.2012.

Research output: Contribution to journalArticle

@article{bffb45eb6df0431fb6dad8ea3bc047ea,
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.",
author = "Elif Eren and Jagamya Vijayaraghavan and Jiaming Liu and Cheneke, {Belete R.} and Touw, {Debra S.} and Lepore, {Bryan W.} and Mridhu Indic and Liviu Movileanu and {van den Berg}, Bert",
year = "2012",
month = "1",
doi = "10.1371/journal.pbio.1001242",
volume = "10",
journal = "PLoS Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Substrate specificity within a family of outer membrane carboxylate channels

AU - Eren,Elif

AU - Vijayaraghavan,Jagamya

AU - Liu,Jiaming

AU - Cheneke,Belete R.

AU - Touw,Debra S.

AU - Lepore,Bryan W.

AU - Indic,Mridhu

AU - Movileanu,Liviu

AU - van den Berg,Bert

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84863012509&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863012509&partnerID=8YFLogxK

U2 - 10.1371/journal.pbio.1001242

DO - 10.1371/journal.pbio.1001242

M3 - Article

VL - 10

JO - PLoS Biology

T2 - PLoS Biology

JF - PLoS Biology

SN - 1544-9173

IS - 1

M1 - e1001242

ER -