Microsporidian coinfection reduces fitness of a fungal pathogen due to rapid host mortality.

Infection outcomes can be strongly context dependent, shifting a host-symbiont relationship along a parasitism-mutualism continuum. Numerous studies show that under stressful conditions, symbionts that are typically mutualistic can become parasitic. The reverse possibility, a parasite becoming mutualistic, has received much less study. We investigated whether the parasitic microsporidium can become beneficial for its host in the presence of the more virulent fungal pathogen . We found that, even though infection with reduces the frequency of penetration of spores into the host body cavity, it does not improve the survival or reproduction of the host; conversely, coinfection increased the mortality of . This shorter lifespan of coinfected hosts disrupted the life cycle of , greatly reducing its fitness. Thus, coinfection with both pathogens was detrimental to the host at the individual level but might be beneficial for the host population as a result of greatly reduced production of spores. If so, this would mean that outbreaks should delay or prevent outbreaks. In support of this, in an analysis of dynamics of naturally occurring outbreaks in two lakes where these pathogens co-occur, we found a time lag in occurrence between and , with epidemics only occurring after the collapse of epidemics. Thus, these results suggest that the interaction between co-occurring symbionts, and the net impact of a symbiont on a host, might be qualitatively different at different scales.IMPORTANCEUnderstanding the factors that modify infection probability and virulence is crucial for identifying the drivers of infection outbreaks and modeling disease epidemic progression, and increases our ability to control diseases and reduce the harm they cause. One factor that can strongly influence infection probability and virulence is the presence of other pathogens. However, while coexposures and coinfections are incredibly common, we still have only a limited understanding of how pathogen interactions alter infection outcomes or whether their impacts are scale dependent. We used a system of one host and two pathogens to show that sequential coinfection can have a tremendous impact on the host and the infecting pathogens and that the outcome of (co-)infection can be negative or positive depending on the focal organization level.