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SUMMARY:Tubercular mycobacteria can escape their proliferation niche and s
 pread from cell to cell via an ejection structure
DTSTART:20090108T121500
DTSTAMP:20260528T120303Z
UID:e2b935a3fc7ef94ce1d6b6fc4a76a162d6bd7d86fb49a0ea708cf0a1
CATEGORIES:Conferences - Seminars
DESCRIPTION:Thierry Soldati\nTubercular mycobacteria such as M. tuberculos
 is and M. marinum utilise common strategies to invade phagocytes of the in
 nate immune system\, manipulate their otherwise bactericidal phagocytic ap
 paratus and increase the success of cell-to-cell transmission. M. marinum 
 is the closest relative to the tuberculosis group of mycobacteria and prov
 ides a powerful model to study the pathogenesis of tuberculosis in genetic
 ally tractable model organisms\, such as Drosophila and zebrafish. Using t
 he soil amoeba Dictyostelium discoideum as a host\, we have identified and
  characterized mycobacterial and host factors that modulate resistance to 
 infection and cell-to-cell spreading (Hagedorn & Soldati\, Cell Microbiol\
 , 2007\, 9:2716-33)\nIn particular\, we discovered that both M. marinum an
 d M. tuberculosis can escape from their vacuole into the cytosol\, and are
  ejected from the cell through an F-actin structure\, the ejectosome. This
  appears to be a conserved strategy because\, upon infection of human peri
 pheral blood monocytes and murine microglial cells\, flotillin-1 accumulat
 ion at the M. marinum replication niche and vacuole rupture were also obse
 rved. Upon ejection of M. marinum\, despite local loss of membrane integri
 ty\, neither host cell leakage nor lysis was observed. Ejection is crucial
  for the maintenance of an infection and is a concerted process that requi
 res both host and pathogen factors. Disruption of the Dictyostelium gene f
 or the RacH GTPase led to intracellular accumulation of bacteria. Also\, n
 o ejectosome was formed in cells infected with M. marinum lacking the majo
 r conserved mycobacterial virulence locus RD1. We propose that this specif
 ic strategy evolved as a necessity for the release of a cytosolic pathogen
  in a mutually beneficial manner\, and discuss its evolutionary origin and
  relevance for dissemination of a mycobacterial infection.
LOCATION:AI 1153 https://plan.epfl.ch/?room==AI%201153
STATUS:CONFIRMED
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