Variation in a microbial mutualist has cascading consequences for host-parasite interactions

Strains of microbial symbionts often vary in their effect on their host. However, little is known about how the genetic variation in microbial symbiont populations impacts host interactions with other co-colonizing microbes. Here we investigated how different strains of nitrogen-fixing rhizobial bacteria affect their host plant’s response to parasitic root-knot nematodes in the legume Medicago truncatula . Using dual RNAseq of the root organs harboring rhizobia or nematodes, we identified genes from plant host, rhizobia, and nematode whose expression differed between parasite-infected and -uninfected plants, and between plants inoculated with different rhizobial strains. At the site of host-parasite interactions (in nematode galls), hundreds of host genes and few nematode genes differed in expression between host plants inoculated with different rhizobia strains. At the site of host-mutualist interactions (in rhizobia nodules), hundreds of host genes and few rhizobial genes responded to parasite infection. The vast majority of parasite-induced changes in host gene expression depended on the resident rhizobia strain. We additionally observed phenotypic differences in the gall and nodule counts on host root systems and in some root architecture traits, showing that genetic variation in a mutualist symbiont impacted parasite colonization rates. The transcriptomic and phenotypic differences we observed suggest that microbial indirect genetic effects play an underappreciated role in structuring their host’s interactions with other co-colonizing microorganisms, which may be mediated by changes in host resource budgets, defense response, or developmental trajectories.