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Broad-spectrum nanoparticles against bacteriophage infections.

ABSTRACT: Viral infections caused by bacteriophages, i.e., viruses that kill bacteria are one of the most dangerous and common threats for bacteria-based bioreactors. More than 70% of biotechnology companies have admitted to encountering this problem. Despite phage infections being such a dangerous and widespread risk, there are no effective methods to avoid them to date. Herein, we present a novel technology based on nanoparticles that irreversibly deactivates bacteriophages and is safe for bacteria. Our method allows for the unsupervised protection of bacterial processes in the biotechnology industry. Gold nanoparticles coated with a mixture of negatively charged 11-mercapto 1-undecanesulfonic acid (MUS) and hydrophobic 1-octanethiol (OT) ligands are effective at deactivating various types of Escherichia coli-selective phages: T1, T4, and T7. The nanoparticles can lower the titer of phages up to 2 and 5 logs in 6 and 24 h at 50 °C, respectively. A comparative analysis of nanoparticles with different ligand shells illustrates the importance of the combination of negatively charged and hydrophobic ligands that is the key to achieving a good inhibitory concentration (EC₅₀ ≤ 1 μg mL^-1) for all tested phages. We show that the nanoparticles are harmless for the commonly used bacteria in industry Escherichia coli and are effective under conditions simulating the environment of bioreactors.

SUBMITTER: Richter L

PROVIDER: S-EPMC8601202 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Broad-spectrum nanoparticles against bacteriophage infections.

Richter Łukasz Ł Paszkowska Karolina K Cendrowska Urszula U Olgiati Francesca F Silva Paulo Jacob PJ Gasbarri Matteo M Guven Zekiye Pelin ZP Paczesny Jan J Stellacci Francesco F

Nanoscale 20211118 44

Viral infections caused by bacteriophages, <i>i.e.</i>, viruses that kill bacteria are one of the most dangerous and common threats for bacteria-based bioreactors. More than 70% of biotechnology companies have admitted to encountering this problem. Despite phage infections being such a dangerous and widespread risk, there are no effective methods to avoid them to date. Herein, we present a novel technology based on nanoparticles that irreversibly deactivates bacteriophages and is safe for bacter ...[more]

PMID: 34738613

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Project description:Invasive fungal infections due to Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans constitute a substantial threat to hospitalized immunocompromised patients. Further, the presence of drug-recalcitrant biofilms on medical devices and emergence of drug-resistant fungi, such as Candida auris, introduce treatment challenges with current antifungal drugs. Worse, currently there is no approved drug capable of obviating preformed biofilms, which increase the chance of infection relapses. Here, we screened a small-molecule New Prestwick Chemical Library, consisting of 1,200 FDA-approved off-patent drugs against C. albicans, C. auris, and A. fumigatus, to identify those that inhibit growth of all three pathogens. Inhibitors were further prioritized for their potency against other fungal pathogens and their ability to kill preformed biofilms. Our studies identified the bis-biguanide alexidine dihydrochloride (AXD) as a drug with the highest antifungal and antibiofilm activity against a diverse range of fungal pathogens. Finally, AXD significantly potentiated the efficacy of fluconazole against biofilms, displayed low mammalian cell toxicity, and eradicated biofilms growing in mouse central venous catheters in vivo, highlighting its potential as a pan-antifungal drug.IMPORTANCE The prevalence of fungal infections has seen a rise in the past decades due to advances in modern medicine leading to an expanding population of device-associated and immunocompromised patients. Furthermore, the spectrum of pathogenic fungi has changed, with the emergence of multidrug-resistant strains such as C. auris High mortality related to fungal infections points to major limitations of current antifungal therapy and an unmet need for new antifungal drugs. We screened a library of repurposed FDA-approved inhibitors to identify compounds with activities against a diverse range of fungi in varied phases of growth. The assays identified alexidine dihydrochloride (AXD) to have pronounced antifungal activity, including against preformed biofilms, at concentrations lower than mammalian cell toxicity. AXD potentiated the activity of fluconazole and amphotericin B against Candida biofilms in vitro and prevented biofilm growth in vivo Thus, AXD has the potential to be developed as a pan-antifungal, antibiofilm drug.

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Broad-spectrum nanoparticles against bacteriophage infections.

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Broad-spectrum nanoparticles against bacteriophage infections.

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