Fig. 1 |. Polymicrobial biogeography can determine the severity of disease and treatment outcomes.

Spatial patterning of bacterial pathogens in relation to other microorganisms can alter the environment, microbial fitness and host immune responses. a | Colonization and aggregate formation by a pathogen (purple), along with the native microbial community (green and blue cells) in the subgingival pocket of the tooth. b | Expansion of the pathogen population can alter the environment by either limiting available nutrients or releasing exoproducts. Inter-species competitive (blue and purple cells) or cooperative (green and purple cells) dynamics determine infection biogeography. In addition, phenotypically and genetically diverse subpopulations can emerge (red cells); this heterogeneity can further alter the nature of intra-species interactions. c | Differential spatial patterning results in changes in virulence. Left side of tooth: localized expansion of pathogen leads to increased virulence, damaging the enamel (red enamel, root and gums) and resulting in periodontitis. This activity amplifies inflammatory signals and recruits immune cells such as neutrophils. In addition, increased pathogen abundance reduces available nutrients, decreasing fitness of the original microbial community. Right side of tooth: dispersed aggregates of the pathogen allow for increased fitness of the original microbial community, preventing both pathogen expansion and heavy damage to the subgingival pocket. d | Antimicrobial treatment is one of the most common disturbances for polymicrobial infections. Outcome of antimicrobial treatment is impacted by biogeography. On left side of tooth, spatial patterning protects the community from antimicrobial treatment. Further, the antibiotic increases fitness of an antibiotic-resistant pathogen (red cells), leading to niche expansion and increased damage. On right side of tooth, spatial patterning allows the pathogen to be susceptible to antibiotic treatment, eliminating the pathogen and reducing abundance of the original microbial community (green cells). This reduces virulence of the community and results in less damage to the tooth.