N-acetyl Cysteine Coated Gallium Particles Demonstrate High Potency against <i>Pseudomonas aeruginosa</i> PAO1

Nosocomial infections pose serious health concerns with over 2 million reported annually in the United States. Many of these infections are associated with bacterial resistance to antibiotics and hence, alternative treatments are critically needed. The objective of this study was to assess the antim...

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Main Authors: Mikaeel Young, Ali Ozcan, Briana Lee, Tyler Maxwell, Thomas Andl, Parthiban Rajasekaran, Melanie J. Beazley, Laurene Tetard, Swadeshmukul Santra
Format: Article
Language:English
Published: MDPI AG 2019-08-01
Series:Pathogens
Subjects:
Online Access:https://www.mdpi.com/2076-0817/8/3/120
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author Mikaeel Young
Ali Ozcan
Briana Lee
Tyler Maxwell
Thomas Andl
Parthiban Rajasekaran
Melanie J. Beazley
Laurene Tetard
Swadeshmukul Santra
author_facet Mikaeel Young
Ali Ozcan
Briana Lee
Tyler Maxwell
Thomas Andl
Parthiban Rajasekaran
Melanie J. Beazley
Laurene Tetard
Swadeshmukul Santra
author_sort Mikaeel Young
collection DOAJ
description Nosocomial infections pose serious health concerns with over 2 million reported annually in the United States. Many of these infections are associated with bacterial resistance to antibiotics and hence, alternative treatments are critically needed. The objective of this study was to assess the antimicrobial efficacy of a gallium (Ga)-based particle coated with N-Acetyl Cysteine (Ga-NAC) against <i>Pseudomonas aeruginosa</i> PAO1. Our studies showed the Minimum Inhibitory Concentration (MIC) of PAO1 treated with Ga-NAC was 1 &#181;g/mL. Cytotoxicity of Ga-NAC against multiple cell lines was determined with no cytotoxicity observed up to concentrations of 2000 &#181;g/mL (metal concentration), indicating a high therapeutic window. To elucidate potential antibacterial modes of action, Inductively Coupled Plasma&#8212;Mass Spectrometry (ICP-MS), infrared spectroscopy, and atomic force microscopy (AFM) were used. The results suggest improved Ga<sup>3+</sup> interaction with PAO1 through Ga-NAC particles. No significant change in cell membrane chemistry or roughening was detected. As cell membrane integrity remained intact, the antimicrobial mode of action was linked to cellular internalization of Ga and subsequent iron metabolic disruption. Furthermore, Ga-NAC inhibited and disrupted biofilms seen with crystal violet assay and microscopy. Our findings suggest the Ga-NAC particle can potentially be used as an alternative to antibiotics for treatment of <i>Pseudomonas aeruginosa</i> infections.
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spelling doaj.art-5b90b1a22fd244209f3ae932f2e2c3632022-12-22T02:14:48ZengMDPI AGPathogens2076-08172019-08-018312010.3390/pathogens8030120pathogens8030120N-acetyl Cysteine Coated Gallium Particles Demonstrate High Potency against <i>Pseudomonas aeruginosa</i> PAO1Mikaeel Young0Ali Ozcan1Briana Lee2Tyler Maxwell3Thomas Andl4Parthiban Rajasekaran5Melanie J. Beazley6Laurene Tetard7Swadeshmukul Santra8Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32816, USANanoScience Technology Center, University of Central Florida, Orlando, FL 32816, USANanoScience Technology Center, University of Central Florida, Orlando, FL 32816, USANanoScience Technology Center, University of Central Florida, Orlando, FL 32816, USABurnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32816, USANanoScience Technology Center, University of Central Florida, Orlando, FL 32816, USADepartment of Chemistry, University of Central Florida, Orlando, FL 32816, USANanoScience Technology Center, University of Central Florida, Orlando, FL 32816, USABurnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32816, USANosocomial infections pose serious health concerns with over 2 million reported annually in the United States. Many of these infections are associated with bacterial resistance to antibiotics and hence, alternative treatments are critically needed. The objective of this study was to assess the antimicrobial efficacy of a gallium (Ga)-based particle coated with N-Acetyl Cysteine (Ga-NAC) against <i>Pseudomonas aeruginosa</i> PAO1. Our studies showed the Minimum Inhibitory Concentration (MIC) of PAO1 treated with Ga-NAC was 1 &#181;g/mL. Cytotoxicity of Ga-NAC against multiple cell lines was determined with no cytotoxicity observed up to concentrations of 2000 &#181;g/mL (metal concentration), indicating a high therapeutic window. To elucidate potential antibacterial modes of action, Inductively Coupled Plasma&#8212;Mass Spectrometry (ICP-MS), infrared spectroscopy, and atomic force microscopy (AFM) were used. The results suggest improved Ga<sup>3+</sup> interaction with PAO1 through Ga-NAC particles. No significant change in cell membrane chemistry or roughening was detected. As cell membrane integrity remained intact, the antimicrobial mode of action was linked to cellular internalization of Ga and subsequent iron metabolic disruption. Furthermore, Ga-NAC inhibited and disrupted biofilms seen with crystal violet assay and microscopy. Our findings suggest the Ga-NAC particle can potentially be used as an alternative to antibiotics for treatment of <i>Pseudomonas aeruginosa</i> infections.https://www.mdpi.com/2076-0817/8/3/120galliumbiofilmMICMBCPseudomonas aeruginosa PAO1
spellingShingle Mikaeel Young
Ali Ozcan
Briana Lee
Tyler Maxwell
Thomas Andl
Parthiban Rajasekaran
Melanie J. Beazley
Laurene Tetard
Swadeshmukul Santra
N-acetyl Cysteine Coated Gallium Particles Demonstrate High Potency against <i>Pseudomonas aeruginosa</i> PAO1
Pathogens
gallium
biofilm
MIC
MBC
Pseudomonas aeruginosa PAO1
title N-acetyl Cysteine Coated Gallium Particles Demonstrate High Potency against <i>Pseudomonas aeruginosa</i> PAO1
title_full N-acetyl Cysteine Coated Gallium Particles Demonstrate High Potency against <i>Pseudomonas aeruginosa</i> PAO1
title_fullStr N-acetyl Cysteine Coated Gallium Particles Demonstrate High Potency against <i>Pseudomonas aeruginosa</i> PAO1
title_full_unstemmed N-acetyl Cysteine Coated Gallium Particles Demonstrate High Potency against <i>Pseudomonas aeruginosa</i> PAO1
title_short N-acetyl Cysteine Coated Gallium Particles Demonstrate High Potency against <i>Pseudomonas aeruginosa</i> PAO1
title_sort n acetyl cysteine coated gallium particles demonstrate high potency against i pseudomonas aeruginosa i pao1
topic gallium
biofilm
MIC
MBC
Pseudomonas aeruginosa PAO1
url https://www.mdpi.com/2076-0817/8/3/120
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