Our group aims to unravel how bacteria evolve in response to abiotic and biotic environmental interactions. We thereby focus on one of the most important players that influence bacterial ecology and evolution: mobile genetic elements (MGEs), including plasmids and phages, which can provide their bacterial hosts with accessory genes, such as virulence and/ or antibiotic resistance genes. By working at different levels of biological complexity, from clonal populations to complex microbial communities, we aim to elucidate phage-bacteria interactions in diverse backgrounds. Utilizing a multidisciplinary approach, we employ a diverse array of techniques such as molecular biology, experimental evolution, in vivo infection experiments, genomics, and mathematical modelling. This holistic approach enables us to explore antimicrobial resistance, infectious diseases, and phage therapy from various angles, leading to a comprehensive understanding of these complex phenomena and advancing phage therapy applications in gut infections.
Our research priorities include the following:
Understanding ecological and evolutionary interactions between prophages, commensals, and pathogens in the gastro-intestinal tract
Reveal the role of prophages in gut health and diseases
Explore how novel insights into phage ecology and evolution can improve phage therapy
Curious about why the natural world is as it is, I studied Biology with a major in Ecology and Evolution at the University of Mainz. After completing my PhD in 2014, I received two postdoctoral fellowships, allowing me to pursue my own research in the lab of Prof. Olivia Roth (Kiel), Prof. Mike Brockhurst (York) and Prof. Alex Hall (Zürich), before I started my own group funded by an SNSF Ambizione Fellowship at ETH Zürich in 2018. In April 2024 my group moved to the Max von Pettenkofer-Institute at LMU Munich, where I hold a W2 Professorship.
Phages are a diverse group of viruses that can infect bacterial cells. As any other virus upon infection and entry into the cell, phages turn the bacterium into a factory designed to produce viral particles which ultimately lyse the bacterium to enter the environment and start a new round of infection (lytic infection). Temperate phages are a specific group of phages characterised by their ability to integrate their genetic material into the bacterial genome (lysogenic infection). In this state they can reside as prophages for many generations along with the host. However, prophages are molecular time bombs that can switch from this dormant state to the lytic state. This switch can happen either spontaneously or in response to environmental stress, such as DNA damage.
Prophages can influence bacterial ecology and evolution in various ways that often extend beyond the bacterium and translate via cascading effects to higher organisms and even entire ecosystems (Wendling 2023). These include beneficial impacts, such as accessory genes encoded on prophages which can for instance alter bacterial pathogenicity, but also negative impacts, such as the risk of lysis. In our group we study how these prophage-mediated impacts affect their ecological and evolutionary interactions with bacteria and how this influences human health and disease.
Understanding phage resistance evolution to advance phage therapy:
Amid the antibiotic resistance crisis, the century-old practice of phage therapy, which uses bacterial viruses to treat bacterial infections, has gained renewed attention. Despite its advantages over antibiotics and extensive research, it has yet to gain momentum due to remaining limitations. These include for instance the evolution of bacterial resistance to therapeutic phages. This is a growing concern which prompts the exploration of various strategies such as directing phage-resistance evolution, which can result in beneficial fitness trade-offs, such as reduced virulence or antibiotic susceptibility. Using experimental evolution we found that phage resistance correlates negatively with bacterial virulence (Wendling et al. 2022). That is, because many phages utilize the same molecular receptor for bacterial cell entry as the pathogen itself uses for host attachment or motility, which may include structures like flagella or pili (Wendling et al. 2022, Goehlich et al. 2023). Such a shared molecular structure creates a unique scenario where the evolution of phage resistance, i.e., modification of the pilus or flagellum, could impose pleiotropic costs in terms of reduced virulence (Wendling et al. 2017, Wendling et al, 2022, Goehlich et al. 2023).
Wendling, C.C.*, Piecyk, A., Refardt, D., Chibani, C.M., Hertel, R., Liesegang, H. Bunk, B., Overmann, J., Roth, O. (2017): “Tripartite species interaction: Eukaryotic hosts suffer more from phage susceptible than from phage resistant bacteria”. BMC Evolutionary Biology
Wendling, C.C.*, Lange, J., Liesegang, H., Sieber, M., Poehlein, A., Bunk, B., Rajkov, J., Goehlich, H., Roth, O., Brockhurst, M. (2022) „Higher phage virulence accelerates the evolution of host resistance” Proceeding of the Royal Society B (289)1984 https://doi.org/10.1098/rspb.2022.1070
Four potential routes through which the impact of prophages on the fitness of their host bacterium extends beyond the prophage-bacterium relationship thereby affecting other organisms and potentially entire ecosystems (Wendling et al. 2023, Current Opinion in Systems Biology
The role of phages in the spread and maintenance of antibiotic resistance genes
Antibiotic resistance genes (ARGs) are often encoded on mobile genetic elements (MGEs), including plasmids and phages. The spread of antibiotic resistance through MGEs poses a significant threat to treating infections, making it crucial to understand how MGEs transfer and interact with each other in natural environments. Most studies focus on MGEs in isolation without considering their interactions. In a recent study, we combined in vitro experiments and mathematical modeling to reveal the influence of prophages on conjugation. We found that prophages can significantly restrict the spread of conjugative plasmids, with this effect varying based on environmental conditions and bacterial genetics (Igler et al. 2022). Simulating a range of infection parameters showed that high conjugation rates could enable plasmids to overcome the negative impact of prophages.
In addition to their spread, the maintenance of MGEs carrying ARGs is of great interest. While prophages encoding ARGs can be highly beneficial for bacteria in the presence of antibiotics (Wendling et al. 2020), the ability of prophages to switch back to the lytic cycle puts bacteria at constant risk of lysis and death. Our group studies how these contrasting fitness impacts of prophages affect their ecological and evolutionary interactions with bacteria. Using experimental evolution, we found that prophages quickly disappear from a bacterial population in environments that enhance the switch from the lysogenic to the lytic cycle. In contrast, prophages carrying beneficial genes can persist despite frequent induction (Bailey et al., 2024).
Bailey, Z.M., Igler, C., Wendling, C.C*. (2024) „Prophage maintenance is determined by environment-dependent selective sweeps rather than mutational availability” Current Biology https://doi.org/10.1016/j.cub.2024.03.025
Igler, C., Schwyter, L., Gehrig, D., Wendling, C.C.* (2022) „Conjugative plasmid transfer is limited by prophages but can be overcome by high conjugation rates” Phil Trans B. (377)1842
Wendling, C.C.*, Refardt, D., Hall, A.R. (2020) “Fitness benefits to bacteria of carrying prophages and prophage-encoded antibiotic-resistance genes peak in different environments” Evolution 75(2) https://doi.org/10.1111/evo.14153
Publications
Top 10 Publikationen
1. Bailey, Z.M.*, Igler, C., Wendling, C.C.* (2024) „Prophage maintenance is determined by environment-dependent selective sweeps rather than mutational availability” Current Biology https://doi.org/10.1016/j.cub.2024.03.025
2. Wendling, C.C.* (2023) “Prophage mediated control of higher order interactions - insights from systems approaches”. Current Opinion in Systems Biology https://doi.org/10.1016/j.coisb.2023.100469
4. Kupczok, A.*, Bailey, Z.M., Refardt, D., Wendling, C.C. (2022) “Co-transfer of functionally interdependent genes contributes to genome mosaicism in lambdoid phages” Microbial Genomics 8(11). https://doi.org/10.1099/mgen.0.000915
5. Igler, C., Schwyter, L., Gehrig, D., Wendling, C.C.* (2022) „Conjugative plasmid transfer is limited by prophages but can be overcome by high conjugation rates” Phil Trans B. (377)1842 https://doi.org/10.1098/rstb.2020.0470
6. Wendling, C.C.*, Lange, J., Liesegang, H., Sieber, M., Poehlein, A., Bunk, B., Rajkov, J., Goehlich, H., Roth, O., Brockhurst, M. (2022) „Higher phage virulence accelerates the evolution of host resistance.” Proceeding of the Royal Society B (289)1984 https://doi.org/10.1098/rspb.2022.1070
7. Wendling, C.C.*, Refardt, D., Hall, A.R. (2020) “Fitness benefits to bacteria of carrying prophages and prophage-encoded antibiotic-resistance genes peak in different environments” Evolution 75(2) https://doi.org/10.1111/evo.14153
8. Chibani, C.M., Roth, O., Liesegang, H. Wendling, C.C.* (2020). “Genomic Variation among closely related Vibrio alginolyticus strains is located on mobile genetic elements”. BMC Genomics 21(235) https://doi.org/10.1186/s12864-020-6735-5
9. Wendling, C.C.*, Goehlich, H., Roth, O. (2018) „The structure of temperate phage-bacteria infection networks changes with the phylogenetic distance of the host bacteria”. Biology Letters 14 (11) https://doi.org/10.1098/rsbl.2018.0320
10. Wendling, C.C.*, Piecyk, A., Refardt, D., Chibani, C.M., Hertel, R., Liesegang, H. Bunk, B., Overmann, J., Roth, O. (2017): "Tripartite species interaction: Eukaryotic hosts suffer more from phage susceptible than from phage resistant bacteria". BMC Evolutionary Biology https://doi.org/10.1186/s12862-017-0930-2
Awards
2018 SNSF Ambizione Fellowship
2018 Marie SkŁodowska-CURIE Intra-European Fellowship
