Bacterial infections still present a major threat to human health worldwide as resistance of pathogenic bacteria to available antibiotics is rapidly increasing.
In this light, the investigation of host-pathogen interactions and the underlying mechanisms is of growing interest. New insights into pathogenesis and the mode of action of bacterial toxins could help to identify new potential targets for the development of innovative therapies.
ETOX is a label for a well-established and reputed series of “European Workshops on Bacterial Protein Toxins” initiated in 1983. Its aim is to bring together the world’s leading experts from different fields, from classical biology to modern structural biology using cryo electron microscopy. But also to give young scientists the opportunity to present and discuss their work in a relaxed atmosphere.
Recent Updates in Bacterial Protein Toxin Research
Decoy exosomes provide protection against bacterial toxins
The research groups of Ken Cadwell from the NYU Grossmann School of Medicine and Victor Torrees from the NYU Langone Medical Center have revealed how host cells can protect themselves from MRSA toxin by activating autophagy and releasing decoy.
Keller MD, Ching KL, Liang FX, Dhabaria A, Tam K, Ueberheide BM, Unutmaz D, Torres VJ, Cadwell K (2021). Decoy exosomes provide protection against bacterial toxins. Nature.
How Bacteria deliver their Toxins
Bacteria have developed highly varied strategies and mechanisms to introduce their poisons into organisms. They use so-called Tc toxins which consist of several components (TcA, TcB, TcC). The video shows the Tc Toxin mode of action mechanism unraveled by the lab of Stefan Raunser from the Max Planck Institute of Molecular Physiology.
Gatsogiannis C, Merino F, Roderer D, Balchin D, Schubert E, Kuhlee A, Hayer-Hartl M, Raunser S. (2018). Tc toxin activation requires unfolding and refolding of a β-propeller. Nature
Salmonella Typhi hijacks host cell ageing through the typhoid toxin
Ageing organisms are more vulnerable to infectious disease due to cellular deterioration in our tissues and immune system that accumulate DNA damage resulting in a hallmark of ageing called senescence. The research group of Daniel Humphreys at the University of Sheffield have discovered that the typhoid toxin of Salmonella Typhi hijacks host senescence during infection, which implicates premature ageing in the virulence mechanisms underlying typhoid fever and chronic infection. Read our Blog at Take on Typhoid. Watch our animation on typhoid and senescence.
Ibler AEM, ElGhazaly M, Naylor KL, Bulgakova NA, F. El-Khamisy S, Humphreys D (2019) Typhoid toxin exhausts the RPA response to DNA replication stress driving senescence and Salmonella infection. Nature Communications, 10(1).
Infection with typhoid-producing Salmonella enteria
Using as model a typhoid toxin-producing Salmonella Typhimurium, the Frisan group have demonstrated that the presence of a functional genotoxin causes DNA fragmentation and senescence in vivo, which unexpectedly is not associated with inflammation, but rather with an anti-inflammatory T helper-2-like response.
This anti-inflammatory effect is lost in mice suffering from acute colitis.
Our data highlight a complex microenvironment-dependent crosstalk between bacterial genotoxins-induced DNA damage response and the regulation of host immune response, underlining the unanticipated role of bacterial genotoxins as immunomodulators.
Océane C.B. Martin, Anna Bergonzini, Maria Lopez Chiloeches, Eleni Paparouna, Deborah Butter, Sofia D.P. Theodorou, Maria M. Haykal, Elisa Boutet-Robinet, Toma Tebaldi, Andrew Wakeham, Mikael Rhen, Vassilis G. Gorgoulis, Tak Mak, Ioannis S. Pateras, and Teresa Frisan. Influence of the microenvironment on the modulation of the host response by the typhoid toxin. Cell Reports 3, 108931 (2019)