Browsing by Author "Koo, Hyun"

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    Farnesol Delivery via Polymeric Nanoparticle Carriers Inhibits Cariogenic Cross-Kingdom Biofilms and Prevents Enamel Demineralization
    (Wiley, 2022) Ito, Tatsuro; Sims, Kenneth R., Jr.; Liu, Yuan; Xiang, Zhenting; Arthur, Rodrigo A.; Hara, Anderson T.; Koo, Hyun; Benoit, Danielle S. W.; Klein, Marlise I.; Biomedical and Applied Sciences, School of Dentistry
    Streptococcus mutans and Candida albicans are frequently detected together in the plaque from patients with early childhood caries (ECC) and synergistically interact to form a cariogenic cross-kingdom biofilm. However, this biofilm is difficult to control. Thus, to achieve maximal efficacy within the complex biofilm microenvironment, nanoparticle carriers have shown increased interest in treating oral biofilms in recent years. Here, we assessed the anti-biofilm efficacy of farnesol (Far), a hydrophobic antibacterial drug and repressor of Candida filamentous forms, against cross-kingdom biofilms employing drug delivery via polymeric nanoparticle carriers (NPCs). We also evaluated the effect of the strategy on teeth enamel demineralization. The farnesol-loaded NPCs (NPC+Far) resulted in a 2-log CFU/mL reduction of S. mutans and C. albicans (hydroxyapatite disc biofilm model). High-resolution confocal images further confirmed a significant reduction in exopolysaccharides, smaller microcolonies of S. mutans, and no hyphal form of C. albicans after treatment with NPC+Far on human tooth enamel (HT) slabs, altering the biofilm 3D structure. Furthermore, NPC+Far treatment was highly effective in preventing enamel demineralization on HT, reducing lesion depth (79% reduction) and mineral loss (85% reduction) versus vehicle PBS-treated HT, while NPC or Far alone had no differences with the PBS. The drug delivery via polymeric NPCs has the potential for targeting bacterial-fungal biofilms associated with a prevalent and costly pediatric oral disease, such as ECC.
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    Ferumoxytol Nanoparticles Target Biofilms Causing Tooth Decay in the Human Mouth
    (American Chemical Society, 2021) Liu, Yuan; Huang, Yue; Kim, Dongyeop; Ren, Zhi; Oh, Min Jun; Cormode, David P.; Hara, Anderson T.; Zero, Domenick T.; Koo, Hyun; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Severe tooth decay has been associated with iron deficiency anemia that disproportionally burdens susceptible populations. Current modalities are insufficient in severe cases where pathogenic dental biofilms rapidly accumulate, requiring new antibiofilm approaches. Here, we show that ferumoxytol, a Food and Drug Administration-approved nanoparticle formulation for treating iron deficiency, exerts an alternative therapeutic activity via the catalytic activation of hydrogen peroxide, which targets bacterial pathogens in biofilms and suppresses tooth enamel decay in an intraoral human disease model. Data reveal the potent antimicrobial specificity of ferumoxytol iron oxide nanoparticles (FerIONP) against biofilms harboring Streptococcus mutans via preferential binding that promotes bacterial killing through in situ free-radical generation. Further analysis indicates that the targeting mechanism involves interactions of FerIONP with pathogen-specific glucan-binding proteins, which have a minimal effect on commensal streptococci. In addition, we demonstrate that FerIONP can detect pathogenic biofilms on natural teeth via a facile colorimetric reaction. Our findings provide clinical evidence and the theranostic potential of catalytic nanoparticles as a targeted anti-infective nanomedicine.
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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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    Spatial mapping of polymicrobial communities reveals a precise biogeography associated with human dental caries
    (National Academy of Sciences, 2020-06-02) Kim, Dongyeop; Barraza, Juan P.; Arthur, Rodrigo A.; Hara, Anderson; Lewis, Karl; Liu, Yuan; Scisci, Elizabeth L.; Hajishengallis, Evlambia; Whiteley, Marvin; Koo, Hyun; Anatomy and Cell Biology, School of Medicine
    Tooth decay (dental caries) is a widespread human disease caused by microbial biofilms. Streptococcus mutans, a biofilm-former, has been consistently associated with severe childhood caries; however, how this bacterium is spatially organized with other microorganisms in the oral cavity to promote disease remains unknown. Using intact biofilms formed on teeth of toddlers affected by caries, we discovered a unique 3D rotund-shaped architecture composed of multiple species precisely arranged in a corona-like structure with an inner core of S. mutans encompassed by outer layers of other bacteria. This architecture creates localized regions of acidic pH and acute enamel demineralization (caries) in a mixed-species biofilm model on human teeth, suggesting this highly ordered community as the causative agent. Notably, the construction of this architecture was found to be an active process initiated by production of an extracellular scaffold by S. mutans that assembles the corona cell arrangement, encapsulating the pathogen core. In addition, this spatial patterning creates a protective barrier against antimicrobials while increasing bacterial acid fitness associated with the disease-causing state. Our data reveal a precise biogeography in a polymicrobial community associated with human caries that can modulate the pathogen positioning and virulence potential in situ, indicating that micron-scale spatial structure of the microbiome may mediate the function and outcome of host–pathogen interactions.