NDLI: Cellular Uptake and Localization of Polymyxins in Renal Tubular Cells Using Rationally Designed Fluorescent Probes

Content Provider	PubMed Central
Author	Yun, Bo Azad, Md. A. K. Nowell, Cameron J. Nation, Roger L. Thompson, Philip E. Roberts, Kade D. Velkov, Tony Li, Jian
Copyright Year	2015
Abstract	Polymyxins are cyclic lipopeptide antibiotics that serve as a last line of defense against Gram-negative bacterial superbugs. However, the extensive accumulation of polymyxins in renal tubular cells can lead to nephrotoxicity, which is the major dose-limiting factor in clinical use. In order to gain further insights into the mechanism of polymyxin-induced nephrotoxicity, we have rationally designed novel fluorescent polymyxin probes to examine the localization of polymyxins in rat renal tubular (NRK-52E) cells. Our design strategy focused on incorporating a dansyl fluorophore at the hydrophobic centers of the polymyxin core structure. To this end, four novel regioselectively labeled monodansylated polymyxin B probes (MIPS-9541, MIPS-9542, MIPS-9543, and MIPS-9544) were designed, synthesized, and screened for their antimicrobial activities and apoptotic effects against rat kidney proximal tubular cells. On the basis of the assessment of antimicrobial activities, cellular uptake, and apoptotic effects on renal tubular cells, incorporation of a dansyl fluorophore at either position 6 or 7 (MIPS-9543 and MIPS-9544, respectively) of the polymyxin core structure appears to be an appropriate strategy for generating representative fluorescent polymyxin probes to be utilized in intracellular imaging and mechanistic studies. Furthermore, confocal imaging experiments utilizing these probes showed evidence of partial colocalization of the polymyxins with both the endoplasmic reticulum and mitochondria in rat renal tubular cells. Our results highlight the value of these new fluorescent polymyxin probes and provide further insights into the mechanism of polymyxin-induced nephrotoxicity.
Related Links	http://dx.doi.org/10.1128/aac.01216-15
Ending Page	7496
Page Count	8
Starting Page	7489
File Format	PDF
ISSN	00664804
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	12
Volume Number	59
Language	English
Publisher	American Society for Microbiology
Publisher Date	2015-12-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Pharmacology (medical) Pharmacology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Measuring Polymyxin Uptake by Renal Tubular Cells: Is BODIPY-Polymyxin B an Appropriate Probe?

Reply to “Measuring Polymyxin Uptake by Renal Tubular Cells: Is BODIPY-Polymyxin B an Appropriate Probe?”

Dose Adjustment of Polymyxins for Renal Insufficiency

Human oligopeptide transporter 2 (PEPT2) mediates cellular uptake of polymyxins

Uptake of Polymyxin B into Renal Cells

Mechanism of Active Renal Tubular Efflux of Tenofovir

Endotoxin-tobramycin additive toxicity on renal proximal tubular cells in culture.

Competitive Inhibition of Renal Tubular Secretion of Gemifloxacin by Probenecid▿

Green Fluorescent Diamidines as Diagnostic Probes for Trypanosomes

Cellular Uptake and Localization of Polymyxins in Renal Tubular Cells Using Rationally Designed Fluorescent Probes

Similar Documents

Measuring Polymyxin Uptake by Renal Tubular Cells: Is BODIPY-Polymyxin B an Appropriate Probe?

Reply to “Measuring Polymyxin Uptake by Renal Tubular Cells: Is BODIPY-Polymyxin B an Appropriate Probe?”

Dose Adjustment of Polymyxins for Renal Insufficiency

Human oligopeptide transporter 2 (PEPT2) mediates cellular uptake of polymyxins

Uptake of Polymyxin B into Renal Cells

Mechanism of Active Renal Tubular Efflux of Tenofovir

Endotoxin-tobramycin additive toxicity on renal proximal tubular cells in culture.

Competitive Inhibition of Renal Tubular Secretion of Gemifloxacin by Probenecid▿

Green Fluorescent Diamidines as Diagnostic Probes for Trypanosomes

Cellular Uptake and Localization of Polymyxins in Renal Tubular Cells Using Rationally Designed Fluorescent Probes