Pathogen-pathogen interactions during co-infections

For over a century, bacterial infections have been studied through the lens of the one-microbe, one-disease paradigm. However, it is now clear that multi-pathogen infections are common, and many infectious diseases are inherently polymicrobial. These complex infections can involve a variety of pathogens, including viruses, bacteria, fungi, and parasites, with polyviral and viral-bacterial interactions being the most extensively studied. In this review, we focus on polybacterial infections, providing an in-depth analysis of the diverse strategies bacteria employ to thrive in co-infection scenarios. We examine the mechanisms of bacterial competition, competition avoidance through spatial or temporal separation, and cooperation. Given the association of polymicrobial infections with more severe clinical outcomes and heightened antibiotic tolerance, we also explore novel therapeutic targets to treat these increasingly common and complex infections. Although our review summarizes current knowledge, the vast scope of this phenomenon suggests that many more mechanisms remain undiscovered and warrant further investigation.