Nanodiamonds facilitate killing of intracellular uropathogenic e. Coli in an in vitro model of urinary tract infection pathogenesis

Janaki Kannan Iyer, Alexia Dickey, Parvaneh Rouhani, Anil Kaul, Nirmal Govindaraju, Raj Narain Singh, Rashmi Kaul

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

About 25–44% of women will experience at least one episode of recurrent UTI and the causative agent in over 70% of UTI cases is uropathogenic Escherichia coli (UPEC). UPEC cause recurrent UTI by evading the bladder’s innate immune system through internalization into the bladder epithelium where antibiotics cannot reach or be effective. Thus, it is important to develop novel therapeutics to eliminate these intracellular pathogens. Nanodiamonds (NDs) are biocompatible nanomaterials that serve as promising candidates for targeted therapeutic applications. The objective of the current study was to investigate if 6 or 25 nm NDs can kill extracellular and intracellular UPEC in infected bladder cells. We utilized the human bladder epithelial cell line, T24, and an invasive strain of UPEC that causes recurrent UTI. We found that acid-purified 6 nm NDs displayed greater antibacterial properties towards UPEC than 25 nm NDs (11.5% vs 94.2% CFU/mL at 100 μg/mL of 6 and 25 nm, respectively; P<0.001). Furthermore, 6 nm NDs were better than 25 nm NDs in reducing the number of UPEC internalized in T24 bladder cells (46.1% vs 81.1% CFU/mL at 100 μg/ mL of 6 and 25 nm, respectively; P<0.01). Our studies demonstrate that 6 nm NDs interacted with T24 bladder cells in a dose-dependent manner and were internalized in 2 hours through an actin-dependent mechanism. Finally, internalization of NDs was required for reducing the number of intracellular UPEC in T24 bladder cells. These findings suggest that 6 nm NDs are promising candidates to treat recurrent UTIs.

Original languageEnglish
Article numbere0191020
JournalPLoS ONE
Volume13
Issue number1
DOIs
StatePublished - Jan 2018

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nanodiamonds
Nanodiamonds
urinary tract diseases
uropathogenic Escherichia coli
Uropathogenic Escherichia coli
Urinary Tract Infections
pathogenesis
bladder
Escherichia coli
Urinary Bladder
cells
In Vitro Techniques
nanomaterials
therapeutics
Nanostructures
antibacterial properties
Immune system
Pathogens
Nanostructured materials
actin

Cite this

@article{e2f9e7385e394887881153299e9beefe,
title = "Nanodiamonds facilitate killing of intracellular uropathogenic e. Coli in an in vitro model of urinary tract infection pathogenesis",
abstract = "About 25–44{\%} of women will experience at least one episode of recurrent UTI and the causative agent in over 70{\%} of UTI cases is uropathogenic Escherichia coli (UPEC). UPEC cause recurrent UTI by evading the bladder’s innate immune system through internalization into the bladder epithelium where antibiotics cannot reach or be effective. Thus, it is important to develop novel therapeutics to eliminate these intracellular pathogens. Nanodiamonds (NDs) are biocompatible nanomaterials that serve as promising candidates for targeted therapeutic applications. The objective of the current study was to investigate if 6 or 25 nm NDs can kill extracellular and intracellular UPEC in infected bladder cells. We utilized the human bladder epithelial cell line, T24, and an invasive strain of UPEC that causes recurrent UTI. We found that acid-purified 6 nm NDs displayed greater antibacterial properties towards UPEC than 25 nm NDs (11.5{\%} vs 94.2{\%} CFU/mL at 100 μg/mL of 6 and 25 nm, respectively; P<0.001). Furthermore, 6 nm NDs were better than 25 nm NDs in reducing the number of UPEC internalized in T24 bladder cells (46.1{\%} vs 81.1{\%} CFU/mL at 100 μg/ mL of 6 and 25 nm, respectively; P<0.01). Our studies demonstrate that 6 nm NDs interacted with T24 bladder cells in a dose-dependent manner and were internalized in 2 hours through an actin-dependent mechanism. Finally, internalization of NDs was required for reducing the number of intracellular UPEC in T24 bladder cells. These findings suggest that 6 nm NDs are promising candidates to treat recurrent UTIs.",
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Nanodiamonds facilitate killing of intracellular uropathogenic e. Coli in an in vitro model of urinary tract infection pathogenesis. / Iyer, Janaki Kannan; Dickey, Alexia; Rouhani, Parvaneh; Kaul, Anil; Govindaraju, Nirmal; Singh, Raj Narain; Kaul, Rashmi.

In: PLoS ONE, Vol. 13, No. 1, e0191020, 01.2018.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Iyer, Janaki Kannan

AU - Dickey, Alexia

AU - Rouhani, Parvaneh

AU - Kaul, Anil

AU - Govindaraju, Nirmal

AU - Singh, Raj Narain

AU - Kaul, Rashmi

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