Chronic infection alters pathogen virulence, microbiome composition, and fly physiology across generations.

Abstract

In many insects, parents and offspring share the same environment. Thus, an infection in the parents has the potential to influence offspring defenses. Moreover, infection can also affect other host aspects, including the microbiome, development, and reproduction. To better understand the intergenerational impacts of infection, we assessed the effects of challenge by the gut pathogen Pseudomonas entomophila (Pe) on Drosophila melanogaster. We found that parental challenge by Pe led to environmental transmission of the pathogen from parents to offspring, resulting in a persistent infection among the population. Pe is a highly virulent pathogen; however, we found that persistent infection was correlated with a loss of pathogen virulence across generations. We explored the impact of chronic pathogen exposure on host physiological traits. Our results showed that pathogen load, virulence, and pathogen-induced microbiome remodeling influence fecundity and starvation resistance. Current research in Drosophila and other insects has shown that immune status can be transmitted to the next generation (transgenerational immunity). Since the offspring were continuously exposed to the pathogen, we explored their response to a new infection. Even though we did not find a protective effect, we observed alterations in gene expression and microbiome remodeling following a new Pe challenge that was dependent on the parental treatment. Altogether, our results provide evidence that the pathogen adapted across generations as part of a tolerance mechanism that allows the pathogen to persist in the environment, which confers a greater probability of survival in subsequent generations. However, chronic exposure to the pathogen resulted in a cost to the host by altering several aspects of host physiology. Author summaryInfection impacts many aspects of animal physiology, including priming host immune responses to repeated pathogen exposure. Whether parental experiences with a pathogen can influence such responses in offspring is less certain. Here, to further our understanding of generational impacts of infection, we studied the interaction between host immunity, the microbiome, and a gut pathogen across generations using the model organism Drosophila melanogaster. Our results showed that parental challenge established a persistent infection in the population, such that offspring were chronically exposed to the pathogen. This chronic pathogen exposure impacted many host physiological traits, but did not confer protection to re-infection with a high-dose of the pathogen. Instead, we found that the transmitted infection led to a loss of pathogen virulence in offspring. At the same time, pathogen density, virulence, and pathogen-induced microbiome remodeling influenced fecundity and starvation resistance. Overall, our results highlight that infection in parents can influence intergenerational responses due to impacts both on the microbiome and on selection on pathogen virulence. Such chronic interactions with the pathogen, even reduced in virulence, alter host physiology.