Molecular mechanisms of co-infections.

Co-infections generally cause exacerbated pathologies in patients, yet a knowledge gap between clinical data and the underlying molecular mechanisms remains. Clinical studies focus on patient outcome, but much less is known about molecular mechanisms and convergence points that define the interaction between different pathogens. In this review, we will summarize the current standing of the literature at the various scales of magnitude that co-infections impact: epidemiology, clinical observations, tissue- and organ-specificity, the single-cell level, and molecular mechanisms. Given the scarcity of systematic research across systems, we will focus on molecular interaction points that have been identified, comment on their generalizability and, where required, extrapolate from single-pathogen studies. More research of the host-pathogen-pathogen interface is direly warranted, and we hope to inspire advances addressing the intricate network between two co-occurring pathogens and their host. In addition to direct implications for co-infections, acquiring a better understanding of how microorganisms interact in this complex environment will enable us to better understand single-pathogen infections as well, which can lead to the development of novel treatment approaches.