The biogeography of polymicrobial infection

Key Points The human microbiome and invading pathogens colonize the host as spatially organized polymicrobial (multi-species or multi-strain) communities, exhibiting spatial patterning or 'biogeography' both at the macroscale (across the human body) and microscale levels (within individual infection sites). Host landmarks that drive biogeography include receptors for microbial attachment, physicochemical cues of pH and oxygen, host-derived nutrients, and the immune response. Specific spatial organizations that result from host–microorganism interactions include localized attachment to host surfaces, metabolically optimal positioning along physicochemical or nutritional gradients, and the enforced segregation of the microbiome from the host by the immune system. Polymicrobial interactions also drive spatial organization in multispecies biofilms, generally resulting in either mixed or segregated spatial patterns, depending on the extent of cooperation or competition between community members. Specific polymicrobial interactions that drive microbiogeography include intercellular attachment (within and between species), biofilm remodelling (by making or breaking down the supporting matrix), and the export of diffusible molecules that promote or suppress the growth of neighbouring cells. Spatial organization and the determining community interactions can, in many cases, alter the progression of infection, in what is known as the 'biogeography of infection.' The spatial organization of microbial communities can affect their function, both in the environment and during infections. In this article, Whiteley and colleagues review the factors that govern biogeography during polymicrobial infections and how spatial positioning can influence bacterial virulence. They also discuss how targeting biogeography can be used as a therapeutic strategy. Microbial communities are spatially organized in both the environment and the human body. Although patterns exhibited by these communities are described by microbial biogeography, this discipline has previously only considered large-scale, global patterns. By contrast, the fine-scale positioning of a pathogen within an infection site can greatly alter its virulence potential. In this Review, we highlight the importance of considering spatial positioning in the study of polymicrobial infections and discuss targeting biogeography as a therapeutic strategy.