BURK-6 · Investigation of the Type VI secretion system-associated toxins of Burkholderia thailandensis
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-09-01 → 2018-08-31
- EU contribution
- €276,107
- Participants
- 2
- Scheme
- MSCA-IF-GF
Lines connect the coordinator with its partners.
Results in brief
Investigation of the Type VI secretion system-associated toxins of Burkholderia thailandensis
Problem addressed: Burkholderia pseudomallei causes melioidosis, a neglected tropical infectious disease, which treatment is complicated by long phases of latency and a high antibiotic resistance. Bacterial secretion systems, which act as small syringes, play a central role in infectious diseases by enabling pathogenic bacteria to deliver toxins and virulence factors into infected target cells. Why is this important for society: To date, there is no vaccine against Burkholderia pseudomallei, which is also renown for its high resistance to antibiotic treatment. Uncovering the toxins delivered by Bacterial secretion systems is essential for the understanding of bacterial pathogenesis and the design of new antimicrobial therapies. Overall objectives: Using high-throughput and cross-disciplinary approaches in a surrogate model, this project aims at identifying and characterising novel toxins delivered by Burkholderia pseudomallei, an emerging life-threatening pathogen for which vaccines are unavailable.
Data: CORDIS, © European Union
Project objective
Secretion systems are evolved machineries enabling bacteria to deliver toxins and virulence factors, called effectors, into target cells to enable the onset of infectious diseases. Uncovering these effectors is essential for the understanding of bacterial pathogenesis and the establishment of appropriate therapeutic strategies to tackle infectious diseases. The recently identified Type Six Secretion System (T6SS) is conserved in environmental and pathogenic Gram-negative bacteria. The T6SS is an organelle structurally akin to an intracellular and membrane-bound contractile phage tail used for the delivery of toxins into prokaryotic and eukaryotic target cells. The importance of this system in the context of infection is highlighted by its ability to not only target eukaryotic cells during bacterial infection, but additionally to target other bacteria co-infecting mammalian and plant hosts. Despite the recent advances made in understanding the mechanisms underlying the T6SS dynamic, very little is known about the T6SS effectors repertoire used by life-threatening pathogens, such as Burkholderia pseudomallei, and for which, vaccine strategies are currently unavailable. In the proposed research, a combination of high-throughput and cross-disciplinary technologies will be used to uncover and characterise novel T6SS effectors in B. thailandensis, a surrogate organism closely related to B. pseudomallei. This will 1) identify new T6SS effectors targeting eukaryotic cells, using a reporter-based transposon screening and 2) identify novel T6SS toxins targeting prokaryotic cells, using a genome-wide saturation mutagenesis strategy. The outcomes of the proposed research will identify the key cellular stages hijacked by the T6SS during the infection of a host, while exposing potential new bacterial targets exploitable for the development of novel antimicrobial strategies.
Original text from CORDIS.
Participants
- LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE ROYAL CHARTER · LondonCoordinatorUnited Kingdom
- UNIVERSITY OF MELBOURNE · MelbourneAustralia
Links
Data: CORDIS, © European Union