한빛사논문
Dongyeop Kima,b, Juan P. Barrazac,d,e, Rodrigo A. Arthura,f, Anderson Harag, Karl Lewish, Yuan Liua,i, Elizabeth L. Sciscii, Evlambia Hajishengallisi, Marvin Whiteleyc,d,e,1, and Hyun Kooa,i,j,1
aBiofilm Research Laboratory, Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104; bDepartment of Preventive Dentistry, School of Dentistry, Jeonbuk National University, 54896 Jeonju, Republic of Korea; cSchool of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332; dEmory-Children’s Cystic Fibrosis Center, Atlanta, GA 30322; eCenter for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, GA 30332; fPreventive and Community Dentistry Department, Dental School, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; gDepartment of Cariology, Operative Dentistry and Dental Public Health, Oral Health Research Institute, Indiana University School of Dentistry, Indianapolis, IN 46202; hDepartment of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202; iDivisions of Pediatric Dentistry and Community Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104; and jCenter for Innovation and Precision Dentistry, School of Dental Medicine and School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104
1To whom correspondence may be addressed.
Abstract
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.
dental caries, polymicrobial, biogeography, biofilm, Streptococcus mutans
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