Indirect interactions among co-infecting parasites and a microbial mutualist impact disease progression

Interactions among parasites and other microbes within hosts can impact disease progression, yet study of such interactions has been mostly limited to pairwise combinations of microbes. Given the diversity of microbes within hosts, indirect interactions among more than two microbial species may also impact disease. To test this hypothesis, we performed inoculation experiments that investigated interactions among two fungal parasites, Rhizoctonia solani and Colletotrichum cereale, and a systemic fungal endophyte, Epichloë coenophiala, within the grass, tall fescue (Lolium arundinaceum). Both direct and indirect interactions impacted disease progression. While the endophyte did not directly influence R. solani disease progression or C. cereale symptom development, the endophyte modified the interaction between the two parasites. The magnitude of the facilitative effect of C. cereale on the growth of R. solani tended to be greater when the endophyte was present. Moreover, this interaction modification strongly affected leaf mortality. For plants lacking the endophyte, parasite co-inoculation did not increase leaf mortality compared to single-parasite inoculations. By contrast, for endophyte-infected plants, parasite co-inoculation increased leaf mortality compared to inoculation with R. solani or C. cereale alone by 1.9 or 4.9 times, respectively. Together, these results show that disease progression can be strongly impacted by indirect interactions among microbial symbionts.