From Binary Model Systems to the Human Microbiome: Factors That Drive Strain Specificity in Host-Symbiont Associations

Microbial symbionts are ubiquitous and can have significant impact on hosts. These impacts can vary in the sign (positive or negative) and degree depending on the identity of the interacting partners. Studies on host-symbiont associations indicate that subspecies (strain) genetic variation can influence interaction outcomes, making it necessary to go beyond species-level distinction to understand host-symbiont dynamics. In this review, we discuss examples of strain specificity found in host-symbiont associations, from binary model systems to the human microbiome. Although host and bacterial factors identified as mediators for specificity could be distinct at the molecular level, they generally fall into two broad functional categories: (1) those that contribute a required activity in support of the association and (2) those involved in antagonistic interactions with organisms outside of the association. We argue here based on current literature that factors from these two categories can work in concert to drive strain specificity and that this strain specificity must be considered to fully understand the molecular and ecological dynamics of host-symbiont associations, including the human microbiome.