Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR
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Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR. / Prabhala, Bala K; Aduri, Nanda G; Iqbal, Mazhar; Rahman, Moazur; Gajhede, Michael; Hansen, Paul R; Mirza, Osman.
In: Research in Microbiology, Vol. 168, No. 5, 16.02.2017, p. 443-449.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR
AU - Prabhala, Bala K
AU - Aduri, Nanda G
AU - Iqbal, Mazhar
AU - Rahman, Moazur
AU - Gajhede, Michael
AU - Hansen, Paul R
AU - Mirza, Osman
N1 - Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
PY - 2017/2/16
Y1 - 2017/2/16
N2 - Proton-dependent oligopeptide transporters (POTs) are secondary active transporters found in all kingdoms of life. POTs utilize the proton electrochemical gradient for the uptake of nutrient dipeptides and tripeptides. The human POT hPepT1 is known to transport a number of drugs. As part of ongoing studies on substrate specificities of POTs from Escherichia coli, our aim in this study was to investigate whether bacterial POTs could also transport these drugs. For this, we selected the common orally administered drugs sulpiride, bestatin, valacyclovir, ampicillin and oseltamivir, that are all transported by hPepT1. The transport of these drugs was evaluated using the prototypical POT YdgR from E. coli. The transport studies were pursued through combining cell-based assays with liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. These investigations revealed that YdgR from E. coli is able to transport five (sulpiride, bestatin, valacyclovir, ampicillin and oseltamivir) drugs. Furthermore, cells not overexpressing YdgR were also able to transport these drugs in a POT-like manner. Orthologues of YdgR are found in several species in the gut microbiome; hence, our findings could have implications for further understanding about the interaction between gut microbes and orally administered drugs.
AB - Proton-dependent oligopeptide transporters (POTs) are secondary active transporters found in all kingdoms of life. POTs utilize the proton electrochemical gradient for the uptake of nutrient dipeptides and tripeptides. The human POT hPepT1 is known to transport a number of drugs. As part of ongoing studies on substrate specificities of POTs from Escherichia coli, our aim in this study was to investigate whether bacterial POTs could also transport these drugs. For this, we selected the common orally administered drugs sulpiride, bestatin, valacyclovir, ampicillin and oseltamivir, that are all transported by hPepT1. The transport of these drugs was evaluated using the prototypical POT YdgR from E. coli. The transport studies were pursued through combining cell-based assays with liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. These investigations revealed that YdgR from E. coli is able to transport five (sulpiride, bestatin, valacyclovir, ampicillin and oseltamivir) drugs. Furthermore, cells not overexpressing YdgR were also able to transport these drugs in a POT-like manner. Orthologues of YdgR are found in several species in the gut microbiome; hence, our findings could have implications for further understanding about the interaction between gut microbes and orally administered drugs.
KW - Journal Article
U2 - 10.1016/j.resmic.2017.01.005
DO - 10.1016/j.resmic.2017.01.005
M3 - Journal article
C2 - 28214542
VL - 168
SP - 443
EP - 449
JO - Research in Microbiology
JF - Research in Microbiology
SN - 0923-2508
IS - 5
ER -
ID: 174424329