Project Details
Projekt
Virulence evolution inside a host: Staphylococcus aureus, antibiotics, and the insect immune system
Applicant
Dr. Flor Inés Arias Sánchez
Subject Area
Evolution, Anthropology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 425876005
Recent discoveries show that Staphylococcus aureus living on the skin of human patients can (via adaptive evolution) switch from commensal to pathogen and cause severe infections. Yet, the causes leading the transition to high virulence remain unknown. Two of the main selective pressures for pathogen survival inside a host are medical interventions (antibiotics) and the immune system. While pairwise effects in vitro are documented, there is an increasing demand to include higher order interactions with the immune system. The goal of this research proposal is to tackle this important challenge and discover the evolutionary trajectories of S. aureus inside insect hosts with manipulated immune responses and/or the presence of low doses of antibiotics. The proposed insect-host model system allows precise manipulation of immune responses without losing the high levels of replication required for evolutionary experiments. Using a combination of different research methods, such as microbial experimental evolution, genomics and mathematical modelling, we will focus on four hypotheses: 1. Evolving S. aureus mutants with diverse immune responses (AMP profiles) will lead to significant variations in pathogen virulence. 2. The presence of low doses of mutagenic antibiotics during within-host evolution will act as a double-edge sword against the host by either increasing bacterial mutation rates or altering immune responses. 3. Virulence patterns of evolved S. aureus mutants will differ when tested against “novel hosts”. 4. Virulence changes not only as a side-effect of evolutionary changes in bacterial population size, but also independently (per-parasite pathogenicity). From a fundamental point of view, this proposal will contribute to understand the routes through which stress may affect ecology and evolution inside a host. Gained insights will potentially inform new strategies to prevent the spread of virulence in one of our most important bacterial pathogens worldwide.
DFG Programme
Research Units
