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Research overview

jeudi 11 octobre 2012, par nicolas

Systems biology of Ehrlichia infection

Infectious Strategies of Anaplasmataceae

My research focus is on how the obligate tick-borne intracellular pathogen Ehrlichia ruminantium (Anaplasmataceae family) manipulates cellular function in order to multiply inside host cells and cause infectious disease.

Heartwater disease caused by E. ruminantium is generally fatal on ruminants and is common in sub-Saharan Africa and in some Caribbean islands. Some human cases have been reported in South Africa. The clinical signs of heartwater (also known as cowdriosis) are caused by an increased vascular permeability and consequent œdema. The symptoms include neurological signs (tremors), respiratory signs (coughing) and systemic signs (fever, loss of appetite).

In the host, E. ruminantium infects endothelial cells and neutrophils, where the pathogen replicates to high numbers in an intracellular vacuole. Ehrlichia produces a Type IV Secretion System (T4SS) to deliver proteins into the host cytoplasm where they can manipulate the host cell machinery and subvert host innate immunity. However, due to a lack of methods for genetic manipulation of the bacterium, Ehrlichia virulence factors remain largely unknown.

Using bioinformatics, genomics, proteomics, cellular and molecular biology approaches, we aim to identify E. ruminantium T4SS substrates and their host targets.

Jeremy Calli

The three major points I am particularly interested in are :

  • How does E. ruminantium attach to host cell and subvert host cell signaling pathways to establish a safe replicating vacuole ?
  • How does E. ruminantium exit host cells and disseminate within a host ?
  • Which mechanisms govern E. ruminantium host specificity ?

Our studies will provide information about the molecular arsenal used by E. ruminantium and other Anaplasmataceae for successful development inside its host cell. We are also studying the impact of these bacteria on host cells signaling.
Altogether, our research will give new insights on the intimate interaction of Anaplasmataceae with their mammalian or tick host cells and will foster the development of new anti-bacterial molecules.

Portfolio

  • Systems biology of Ehrlichia infection

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