Browsing by Author "Simon-Soro, Aurea"

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    Interkingdom assemblages in human saliva display group-level surface mobility and disease-promoting emergent functions
    (National Academy of Science, 2022) Ren, Zhi; Jeckel, Hannah; Simon-Soro, Aurea; Xiang, Zhenting; Liu, Yuan; Cavalcanti, Indira M.; Xiao, Jin; Tin, Nyi-Nyi; Hara, Anderson; Drescher, Knut; Koo, Hyun; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Fungi and bacteria form multicellular biofilms causing many human infections. How such distinctive microbes act in concert spatiotemporally to coordinate disease-promoting functionality remains understudied. Using multiscale real-time microscopy and computational analysis, we investigate the dynamics of fungal and bacterial interactions in human saliva and their biofilm development on tooth surfaces. We discovered structured interkingdom assemblages displaying emergent functionalities to enhance collective surface colonization, survival, and growth. Further analyses revealed an unexpected group-level surface mobility with coordinated “leaping-like” and “walking-like” motions while continuously growing. These mobile groups of growing cells promote rapid spatial spreading of both species across surfaces, causing more extensive tooth decay. Our findings show multicellular interkingdom assemblages acting like supraorganisms with functionalities that cannot be achieved without coassembly.
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    Topical ferumoxytol nanoparticles disrupt biofilms and prevent tooth decay in vivo via intrinsic catalytic activity
    (Springer Nature, 2018-07-31) Liu, Yuan; Naha, Pratap C.; Hwang, Geelsu; Kim, Dongyeop; Huang, Yue; Simon-Soro, Aurea; Jung, Hoi-In; Ren, Zhi; Li, Yong; Gubara, Sarah; Alawi, Faizan; Zero, Domenick; Hara, Anderson T.; Cormode, David P.; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Ferumoxytol is a nanoparticle formulation approved by the U.S. Food and Drug Administration for systemic use to treat iron deficiency. Here, we show that, in addition, ferumoxytol disrupts intractable oral biofilms and prevents tooth decay (dental caries) via intrinsic peroxidase-like activity. Ferumoxytol binds within the biofilm ultrastructure and generates free radicals from hydrogen peroxide (H2O2), causing in situ bacterial death via cell membrane disruption and extracellular polymeric substances matrix degradation. In combination with low concentrations of H2O2, ferumoxytol inhibits biofilm accumulation on natural teeth in a human-derived ex vivo biofilm model, and prevents acid damage of the mineralized tissue. Topical oral treatment with ferumoxytol and H2O2 suppresses the development of dental caries in vivo, preventing the onset of severe tooth decay (cavities) in a rodent model of the disease. Microbiome and histological analyses show no adverse effects on oral microbiota diversity, and gingival and mucosal tissues. Our results reveal a new biomedical application for ferumoxytol as topical treatment of a prevalent and costly biofilm-induced oral disease.