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      Antimicrobial Activities and Mechanisms of Magnesium Oxide Nanoparticles (nMgO) against Pathogenic Bacteria, Yeasts, and Biofilms

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          Abstract

          Magnesium oxide nanoparticle (nMgO) is a light metal based antimicrobial nanoparticle that can be metabolized and fully resorbed in the body. To take advantage of the antimicrobial properties of nMgO for medical use, it is necessary to determine the minimal inhibitory, bactericidal and fungicidal concentrations (MIC, MBC and MFC) of nMgO against prevalent infectious bacteria and yeasts. The objective of this study was to use consistent methods and conditions to reveal and directly compare the efficacy of nMgO against nine prevalent pathogenic microorganisms, including two gram-negative bacteria, three gram-positive bacteria with drug-resistant strains, and four yeasts with drug-resistant strains. The MIC of nMgO varied from 0.5 mg/mL to 1.2 mg/mL and the minimal lethal concentration (MLC) of nMgO at 90% killing varied from 0.7 mg/mL to 1.4 mg/mL against different pathogenic bacteria and yeasts. The most potent concentrations (MPC) of nMgO were 1.4 and/or 1.6 mg/mL, depending on the type of bacteria and yeasts tested. As the concentration of nMgO increased, the adhesion of bacteria and yeasts decreased. Moreover, S. epidermidis biofilm was disrupted at 1.6 mg/mL of nMgO. E. coli and some yeasts showed membrane damage after cultured with ≥0.5 mg/mL nMgO. Overall, nMgO killed both planktonic bacteria and disrupted nascent biofilms, suggesting new antimicrobial mechanisms of nMgO. Production of reactive oxygen species (ROS), Ca 2+ ion concentrations, and quorum sensing likely contribute to the action mechanisms of nMgO against planktonic bacteria, but transient alkaline pH of 7 to 10 or increased Mg 2+ ion concentrations from 1 to 50 mM showed no inhibitory or killing effects on bacteria such as S. epidermidis. Further studies are needed to determine if specific concentrations of nMgO at MIC, MLC or MPC level can be integrated into medical devices to evoke desired antimicrobial responses without harming host cells.

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          Biofilms and device-associated infections.

          Microorganisms commonly attach to living and nonliving surfaces, including those of indwelling medical devices, and form biofilms made up of extracellular polymers. In this state, microorganisms are highly resistant to antimicrobial treatment and are tenaciously bound to the surface. To better understand and control biofilms on indwelling medical devices, researchers should develop reliable sampling and measurement techniques, investigate the role of biofilms in antimicrobial drug resistance, and establish the link between biofilm contamination and patient infection.
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            Antifungal agents: mechanisms of action

            Clinical needs for novel antifungal agents have altered steadily with the rise and fall of AIDS-related mycoses, and the change in spectrum of fatal disseminated fungal infections that has accompanied changes in therapeutic immunosuppressive therapies. The search for new molecular targets for antifungals has generated considerable research using modern genomic approaches, so far without generating new agents for clinical use. Meanwhile, six new antifungal agents have just reached, or are approaching, the clinic. Three are new triazoles, with extremely broad antifungal spectra, and three are echinocandins, which inhibit synthesis of fungal cell wall polysaccharides--a new mode of action. In addition, the sordarins represent a novel class of agents that inhibit fungal protein synthesis. This review describes the targets and mechanisms of action of all classes of antifungal agents in clinical use or with clinical potential.
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              The significance of infection related to orthopedic devices and issues of antibiotic resistance.

              Over the last 15 years, with the advent of modern standards in the control of sterility within the operating room environment and adequate protocols of peri-operative antibiotic prophylaxis, the incidence of infections associated to orthopedic implants has become very low. Nevertheless, the event of infection still represents one of the most serious and devastating complications which may involve prosthetic devices. It leads to complex revision procedures and, often, to the failure of the implant and the need for its complete removal. In orthopedics, for the enormous number of surgical procedures involving invasive implant materials, even if nowadays rare, infections have a huge impact in terms of morbidity, mortality, and medical costs. The difficult battle to prevent and fight bacterial infections associated to prosthetic materials must be played on different grounds. A winning strategy requires a clear view of the pathogenesis and the epidemiology of implant-related infections, with a special attention on the alarming phenomenon of antibiotic resistance. In this regard staphylococci are the prevalent and most important causative pathogens involved in orthopedic implant-related infections, and, thus, the main enemy to defeat. In this paper, we offer an overview of the complexity of this battleground and of the current and new, in our opinion most promising, strategies in the field of biomaterials to reduce the risks and counteract the establishment of implant infections.
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                Author and article information

                Contributors
                huinan.liu@ucr.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                2 November 2018
                2 November 2018
                2018
                : 8
                : 16260
                Affiliations
                [1 ]ISNI 0000 0001 2222 1582, GRID grid.266097.c, Microbiology Graduate Program, , University of California, ; Riverside, CA 92521 USA
                [2 ]ISNI 0000 0001 2222 1582, GRID grid.266097.c, Department of Bioengineering, , University of California, ; Riverside, CA 92521 USA
                [3 ]ISNI 0000 0001 2222 1582, GRID grid.266097.c, Materials Science and Engineering Program, , University of California, ; Riverside, CA 92521 USA
                Author information
                http://orcid.org/0000-0001-9366-6204
                Article
                34567
                10.1038/s41598-018-34567-5
                6214931
                30389984
                3f5197c6-4b5a-4ed2-b2a4-426b27c22113
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 December 2017
                : 19 October 2018
                Funding
                Funded by: U.S. National Science Foundation (Award 1512764, 1545852), the Hellman Faculty Fellowship (Huinan Liu), the U.S. National Institutes of Health (5R03AR069373, 6R43DE023287 and 2R44DE023287), the University of California (UC) Regents Faculty Fellowship (Huinan Liu), and the U.S. Department of Education (the STEM Pathways Program, P031C110131) for supporting undergraduate researcher (N.G.).
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