Step-specific adaptation and trade-off over the course of an infection by GASP-mutation small colony variants
Abstract
During an infection, parasites face a succession of challenges, each decisive for disease outcome. The diversity of challenges requires a series of parasite adaptations to successfully multiply and transmit from host to host. Thus, the pathogen genotypes which succeed during one step might be counter-selected in later stages of the infection. Using the bacteria Xenorhabdus nematophila and adult Drosophila melanogaster as hosts, we showed that such step-specific adaptations, here linked to GASP (i.e. Growth Advantage in Stationary Phase) mutations in the X. nematophila master gene regulator lrp, exist and can trade-off with each other. We found that nonsense lrp mutations had lowered ability to resist the host immune response, while all classes of mutations in lrp were associated with a decrease in the ability to proliferate during early infection. We demonstrate that reduced proliferation of X. nematophila best explains diminished virulence in this infection model. Finally, decreased proliferation during the first step of infection is accompanied with improved proliferation during late infection, suggesting a trade-off between the adaptations to each step. Step specific adaptations could play a crucial role in the chronic phase of infections in any diseases that show similar small colony variants (also known as SCV) to X. nematophila.
