Dataset Information

Delivery of antimicrobials into parasites.

ABSTRACT: To eliminate apicomplexan parasites, inhibitory compounds must cross host cell, parasitophorous vacuole, and parasite membranes and cyst walls, making delivery challenging. Here, we show that short oligomers of arginine enter Toxoplasma gondii tachyzoites and encysted bradyzoites. Triclosan, which inhibits enoyl-ACP reductase (ENR), conjugated to arginine oligomers enters extracellular tachyzoites, host cells, tachyzoites inside parasitophorous vacuoles within host cells, extracellular bradyzoites, and bradyzoites within cysts. We identify, clone, and sequence T. gondii enr and produce and characterize enzymatically active, recombinant ENR. This enzyme has the requisite amino acids to bind triclosan. Triclosan released after conjugation to octaarginine via a readily hydrolyzable ester linkage inhibits ENR activity, tachyzoites in vitro, and tachyzoites in mice. Delivery of an inhibitor to a microorganism via conjugation to octaarginine provides an approach to transporting antimicrobials and other small molecules to sequestered parasites, a model system to characterize transport across multiple membrane barriers and structures, a widely applicable paradigm for treatment of active and encysted apicomplexan and other infections, and a generic proof of principle for a mechanism of medicine delivery.

SUBMITTER: Samuel BU

PROVIDER: S-EPMC283583 | biostudies-literature | 2003 Nov

REPOSITORIES: biostudies-literature

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Delivery of antimicrobials into parasites.

Samuel B U BU Hearn B B Mack D D Wender P P Rothbard J J Kirisits M J MJ Mui E E Wernimont S S Roberts C W CW Muench S P SP Rice D W DW Prigge S T ST Law A B AB McLeod R R

Proceedings of the National Academy of Sciences of the United States of America 20031117 24

To eliminate apicomplexan parasites, inhibitory compounds must cross host cell, parasitophorous vacuole, and parasite membranes and cyst walls, making delivery challenging. Here, we show that short oligomers of arginine enter Toxoplasma gondii tachyzoites and encysted bradyzoites. Triclosan, which inhibits enoyl-ACP reductase (ENR), conjugated to arginine oligomers enters extracellular tachyzoites, host cells, tachyzoites inside parasitophorous vacuoles within host cells, extracellular bradyzoit ...[more]

PMID: 14623959

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Project description:Despite the progress in the area of food safety, foodborne diseases still represent a massive challenge to the public health systems worldwide, mainly due to the substantial inefficiencies across the farm-to-fork continuum. Here, we report the development of a nano-carrier platform, for the targeted and precise delivery of antimicrobials for the inactivation of microorganisms on surfaces using Engineered Water Nanostructures (EWNS). An aqueous suspension of an active ingredient (AI) was used to synthesize iEWNS, with the 'i' denoting the AI used in their synthesis, using a combined electrospray and ionization process. The iEWNS possess unique, active-ingredient-dependent physicochemical properties: i) they are engineered to have a tunable size in the nanoscale; ii) they have excessive electric surface charge, and iii) they contain both the reactive oxygen species (ROS) formed due to the ionization of deionized (DI) water, and the AI used in their synthesis. Their charge can be used in combination with an electric field to target them onto a surface of interest. In this approach, a number of nature-inspired antimicrobials, such as H2O2, lysozyme, citric acid, and their combination, were used to synthesize a variety of iEWNS-based nano-sanitizers. It was demonstrated through foodborne-pathogen-inactivation experiments that due to the targeted and precise delivery, and synergistic effects of AI and ROS incorporated in the iEWNS structure, a pico- to nanogram-level dose of the AI delivered to the surface using this nano-carrier platform is capable of achieving 5-log reductions in minutes of exposure time. This aerosol-based, yet 'dry' intervention approach using iEWNS nano-carrier platform offers advantages over current 'wet' techniques that are prevalent commercially, which require grams of the AI to achieve similar inactivation, leading to increased chemical risks and chemical waste byproducts. Such a targeted nano-carrier approach has the potential to revolutionize the delivery of antimicrobials for sterilization in the food industry.

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Delivery of antimicrobials into parasites.

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Delivery of antimicrobials into parasites.

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