The prototypical proton-coupled oligopeptide transporter YdgR from Escherichia coli facilitates chloramphenicol uptake into bacterial cells
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The prototypical proton-coupled oligopeptide transporter YdgR from Escherichia coli facilitates chloramphenicol uptake into bacterial cells. / Prabhala, Bala K; Aduri, Nanda G; Sharma, Neha; Shaheen, Aqsa; Sharma, Arpan; Iqbal, Mazhar; Hansen, Paul R; Brasen, Christoffer; Gajhede, Michael; Rahman, Moazur; Mirza, Osman.
In: The Journal of Biological Chemistry, Vol. 293, 2018, p. 1007-1017.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The prototypical proton-coupled oligopeptide transporter YdgR from Escherichia coli facilitates chloramphenicol uptake into bacterial cells
AU - Prabhala, Bala K
AU - Aduri, Nanda G
AU - Sharma, Neha
AU - Shaheen, Aqsa
AU - Sharma, Arpan
AU - Iqbal, Mazhar
AU - Hansen, Paul R
AU - Brasen, Christoffer
AU - Gajhede, Michael
AU - Rahman, Moazur
AU - Mirza, Osman
N1 - Copyright © 2017, The American Society for Biochemistry and Molecular Biology.
PY - 2018
Y1 - 2018
N2 - Chloramphenicol (Cam) is a broad-spectrum antibiotic used to combat bacterial infections in humans and animals. Cam export from bacterial cells is one of the mechanisms by which pathogens resist Cam's antibacterial effects, and several different proteins are known to facilitate this process. However, to date no report exists on any specific transport protein that facilitates Cam uptake. The proton-coupled oligopeptide transporter (POT) YdgR from Escherichia coli is a prototypical member of the POT family, functioning in proton-coupled uptake of di- and tripeptides. By following bacterial growth and conducting LC-MS-based assays we show here that YdgR facilitates Cam uptake. Some YdgR variants displaying reduced peptide uptake also exhibited reduced Cam uptake, indicating that peptides and Cam bind YdgR at similar regions. Homology modeling of YdgR, Cam docking, and mutational studies suggested a binding mode that resembles that of Cam binding to the multidrug resistance transporter MdfA. To our knowledge, this is the first report of Cam uptake into bacterial cells mediated by a specific transporter protein. Our findings suggest a specific bacterial transporter for drug uptake that might be targeted to promote greater antibiotic influx in order to increase cytoplasmic antibiotic concentration for enhanced cytotoxicity.
AB - Chloramphenicol (Cam) is a broad-spectrum antibiotic used to combat bacterial infections in humans and animals. Cam export from bacterial cells is one of the mechanisms by which pathogens resist Cam's antibacterial effects, and several different proteins are known to facilitate this process. However, to date no report exists on any specific transport protein that facilitates Cam uptake. The proton-coupled oligopeptide transporter (POT) YdgR from Escherichia coli is a prototypical member of the POT family, functioning in proton-coupled uptake of di- and tripeptides. By following bacterial growth and conducting LC-MS-based assays we show here that YdgR facilitates Cam uptake. Some YdgR variants displaying reduced peptide uptake also exhibited reduced Cam uptake, indicating that peptides and Cam bind YdgR at similar regions. Homology modeling of YdgR, Cam docking, and mutational studies suggested a binding mode that resembles that of Cam binding to the multidrug resistance transporter MdfA. To our knowledge, this is the first report of Cam uptake into bacterial cells mediated by a specific transporter protein. Our findings suggest a specific bacterial transporter for drug uptake that might be targeted to promote greater antibiotic influx in order to increase cytoplasmic antibiotic concentration for enhanced cytotoxicity.
KW - Journal Article
U2 - 10.1074/jbc.M117.805960
DO - 10.1074/jbc.M117.805960
M3 - Journal article
C2 - 29150447
VL - 293
SP - 1007
EP - 1017
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
ER -
ID: 185842508