Oral multispecies biofilm development and the key role of cell–cell distance

Key Points Human oral biofilms are multispecies microbial communities that attach to the surfaces of hard and soft tissues in the mouth. The ease with which these communities can be accessed has enabled detailed investigations into their composition, structure and physiology. Specific adhesive interactions between genetically distinct cell types (coaggregation) contribute to the spatial and temporal development of dental plaque biofilms. Microcommunities that contain coaggregation partners juxtaposed on the enamel surface can be identified and micromanipulated. The partner organisms in one of these communities were grown and analyzed in the laboratory and reconstituted as a multispecies biofilm growing on saliva. In open, flowing systems an important consequence of cell–cell proximity is an ability of the cells to communicate. Many oral bacteria produce autoinducer 2, which is a key signal for intercellular communication in biofilms. The presence of autoinducer 2 in two-species communities containing Streptococcus oralis and Actinomyces oris enables mutualistic growth of both organisms. Oral biofilms contain vast networks of intermicrobial interactions, most of which have yet to be identified. In this respect, oral microbial communities are similar to many other biofilm systems, and studies on oral biofilms have produced a paradigm for many aspects of biofilm biology. Oral biofilms are the paradigm of multispecies biofilms. Paul Kolenbrander and colleagues describe the different steps in the formation of these biofilms, the importance of intercellular cooperation and signalling, and how this can lead to pathogenesis. In all these aspects, the distance between the bacteria is an important factor. Growth of oral bacteria in situ requires adhesion to a surface because the constant flow of host secretions thwarts the ability of planktonic cells to grow before they are swallowed. Therefore, oral bacteria evolved to form biofilms on hard tooth surfaces and on soft epithelial tissues, which often contain multiple bacterial species. Because these biofilms are easy to study, they have become the paradigm of multispecies biofilms. In this Review we describe the factors involved in the formation of these biofilms, including the initial adherence to the oral tissues and teeth, cooperation between bacterial species in the biofilm, signalling between the bacteria and its role in pathogenesis, and the transfer of DNA between bacteria. In all these aspects distance betwee