Integrative evolutionary and ecological analysis of antimicrobial resistance: emergence and transmission from genomic to geographic scale

• Applicants: Professorin Dr. Sofia Forslund-Startceva; Professor Emanuel Heitlinger, Ph.D.; Professorin Dr. Stephanie Kramer-Schadt
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Microbial Ecology and Applied Microbiology ; Ecology and Biodiversity of Animals and Ecosystems, Organismic Interactions
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 497777820

Biological novelty arises from the interplay of evolutionary and ecological processes. The emergence and maintenance of novel traits depends on abiotic and biotic factors at different levels of biological organization, from the molecular level to the levels of organization at which biological communities interact.Bacterial antibiotic resistance (AR) is one such biological phenomenon emergent at multiple levels, and also a priority public health problem. While the selection mechanisms for antibiotic resistance are well understood, the transmission of antibiotic resistance genes (ARGs) is a comparatively under-researched topic. In particular, the links between molecular level, genomic level, bacterial community level, and host community level in the dissemination of ARGs are rarely analyzed in an overarching manner. The ultimate goal of this research project is to clarify the respective roles of geographic landscape configuration, microbiome community, and genomic landscape in the epidemiology of ARGs.To this end, this research project includes six key steps: 1. We will catalog ARGs in rodents to establish priority target ARGs. 2. We will reconstruct complete bacterial genomes using a long-read sequencing approach to give ARGs a genomic context of mobilizing genomic elements. Using this approach, we will also describe a community of genetic elements for each bacterial genome to understand the transmission and persistence of ARGs at this level. 3.We will investigate the influence of the microbiome community on the transmission and persistence of ARGs. 4.We will use phylogenetic similarity of ARGs to estimate transmission pathways and detect signals of selection pressure by antibiotics. 5. We will use statistical and metacommunity simulation models to elucidate the extent to which evolutionary selection leads to persistence of ARGs and the extent to which mobility, both at the genetic and host levels, leads to transmission of ARGs. Finally, 6., we will functionally characterize epidemiologically relevant ARGs. Successful completion of this project will fill gaps in current knowledge of the dynamics of antimicrobial resistance determinants at multiple levels. Given the importance of understanding how bacteria carrying ARGs interact in the microbiome and with the environment of their hosts, our project should also provide useful information for improving strategies to prevent emerging threats of antimicrobial resistance.

• DFG Programme: Research Grants