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The type VI secretion system of Francisella tularensis – elucidation of its structure and assembly/disassembly control

Research project supported by the Swedish Research Council.

Type VI secretion systems (T6SSs) are essential for many bacteria to cause disease. We study the T6SS of the highly aggressive bacterium Francisella tularensis (Ft), the causative agent of tularemia, rabbit fever. We study mechanisms that control the T6SS of Ft with a special focus on the protein ClpB and identify the structure of the secretion system, in particular the base-plate, which forms the physical foundation for the secretion system.

Head of project

Anders Sjöstedt
Professor, senior consultant (attending) physician
E-mail
Email

Project overview

Project period:

2021-01-01 2023-12-31

Participating departments and units at Umeå University

Department of Clinical Microbiology, Faculty of Medicine

Research area

Infection biology, Molecular biology and genetics

External funding

Swedish Research Council

Project description

Type VI secretion systems (T6SSs) are virulence mechanisms used by many clinically relevant Gram-negative pathogens to establish eukaryotic host infections. How these sophisticated multicomponent systems are regulated and assembled is still not fully known. While most systems share a common set of so-called core components, several of these are lacking in the T6SS of Francisella tularensis (Ft). This highly virulent pathogen causes tularemia in humans and many animal species, and depend on its T6SS to invade and replicate within the host cell cytosol.

With regard to Ft T6SS regulation, we have recently identified a critical, but yet not understood, role of the ClpB chaperone. The molecular details of these interactions within the model organism Francisella novicida as well as in the clinically important Ft subspecies, holarctica and tularensis, are under investigation.

We are also investigating the composition and assembly of the Ft T6SS baseplate, the structure that connects the membrane complex with the syringe like tail complex, predicted to deliver toxins into host cells.

References

Athar Alam, Jeanette Bröms, Rajendar Kumar, Anders Sjöstedt. (2021) The role of ClpB in bacterial stress responses and virulence.  In press. Frontiers in Molecular Biosciences.

Athar Alam, Igor Golovliov, Eram Javed, Jörgen Åden, Anders Sjöstedt. (2020). Dissociation between the critical role of ClpB of Francisella tularensis for the heat shock response and the DnaK interaction and its important role for efficient type VI secretion and bacterial virulence. PLoS Pathog. doi: 10.1371/journal.ppat.1008466.

Athar Alam, Igor Golovliov, Anders Sjöstedt. (2018) ClpB mutants of Francisella tularensis subspecies holarctica and tularensis are defective for type VI secretion and intracellular replication. Sci. Rep. 8:11324. DOI: 10.1038/s41598-018-29745-4.

External funding