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Investigation of the Type VI secretion system-associated toxins of Burkholderia thailandensis

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.

Field of science

  • /natural sciences/physical sciences/optics/microscopy/confocal microscopy
  • /medical and health sciences/basic medicine/medicinal chemistry
  • /medical and health sciences/basic medicine/pharmacology and pharmacy/pharmaceutical drug/vaccines
  • /natural sciences/biological sciences/microbiology/bacteriology
  • /medical and health sciences/health sciences/tropical medicine
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/proteomics
  • /medical and health sciences/basic medicine/pharmacology and pharmacy/drug resistance/antibiotic resistance
  • /natural sciences/biological sciences/cell biology
  • /natural sciences/physical sciences/optics/microscopy/electron microscopy
  • /medical and health sciences/basic medicine/immunology

Call for proposal

H2020-MSCA-IF-2014
See other projects for this call

Funding Scheme

MSCA-IF-GF - Global Fellowships

Coordinator

LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE ROYAL CHARTER
Address
Keppel Street
WC1E 7HT London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 276 107,40

Partners (1)

UNIVERSITY OF MELBOURNE
Australia
Address
Parkvilleoffice Of The Vice Chancellor
3010 Melbourne
Activity type
Higher or Secondary Education Establishments