期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 22, 页码 12375-12386出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1919099117
关键词
dental caries; polymicrobial; biogeography; biofilm; Streptococcus mutans
资金
- National Institute for Dental and Craniofacial Research Grants [R01 DE025220, R01 DE018023, R01 DE020100, R01 DE023193]
- NIH [S10 OD021633-1, S10 RR027128-01]
- University of Pennsylvania School of Veterinary Medicine
- Colgate-Palmolive Fellowship in Pediatric Dentistry for the Doctor of Science in Dentistry program at Penn Dental 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.
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