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Zawartość zarchiwizowana w dniu 2024-06-16

The role of the pH inside the Salmonella-containing vacuole on type-III secretion triggering and on bacterial intracellular multiplication

Cel

Type-III secretion (T3S) systems allow Gram-negative pathogenic bacteria to reprogram eukaryotic host cells by injecting effector proteins through a eukaryotic membrane into their cytosol. Salmonella enterica are facultative intracellular enteropathogens t hat infect humans and animals, causing a wide range of diseases.

Salmonella reside and replicate inside host cells in a membrane-bound compartments called Salmonella-containing vacuoles (SCVs), which use a unique trafficking pathway. The Salmonella pathogenicity island-2 (SPI-2) T3S system is required for intracellular bacterial replication. This indicates that SPI-2 effectors, delivered through the vacuolar membrane, act on intracellular trafficking to mediate the creation of a niche permissive for bacteri al multiplication.

The SCVs acidifies to between pH 4.0-5.0 and in vitro SPI-2-mediated T3S is triggered by this pH range. This suggests that acidic pH might be the physiological stimulus for SPI-2-mediated T3S inside the SCV. In this project, we aim to characterize SPI-2 T3S triggering, understand its role in Salmonella pathogenesis, and gain deeper insights on the mechanisms employed by pathogens to modulate intracellular trafficking.

We propose to screen and characterize the gene(s) required for in vitro SPI-2 T3S triggering; investigate the mode of action of the affected protein(s); determine if acidification triggers T3S inside the SCV; and study the influence of vacuolar pH on Salmonella intracellular trafficking and multiplication. We will use a wide genome screening method to study the mechanisms of virulence of a very important human and animal pathogen.

The full understanding of the SPI-2 T3S triggering will open the possibility of developing specific drugs to combat Salmonella infections. Thus, this project fits within the objectives of the 6th Framework Programme, in the category life science, genomic and biotechnology for health.

Dziedzina nauki (EuroSciVoc)

Słowa kluczowe

Temat(-y)

Zaproszenie do składania wniosków

FP6-2004-MOBILITY-5
Zobacz inne projekty w ramach tego zaproszenia

System finansowania

EIF - Marie Curie actions-Intra-European Fellowships

Koordynator

IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
Wkład UE
Brak danych
Koszt całkowity
Brak danych