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SUMMARY:Breaking fat! How mycobacteria become obese in Dictyostelium mutan
 ts lacking lipid droplets!
DTSTART:20160502T140000
DTEND:20160502T150000
DTSTAMP:20260506T184540Z
UID:1686930e61a2685488b159c769da181f6be0d0ef4d207039b3001405
CATEGORIES:Conferences - Seminars
DESCRIPTION:Caroline BARISCH - Université de Genève\nLipid droplets (LDs
 ) store energy in form of neutral lipids and exist in virtually every cell
  type ranging from simple organisms such as bacteria and amoebae to plants
  and mammals. Induction of foamy\, LD-filled macrophages\, is a general ho
 st response to mycobacterial infection and develops shortly after granulom
 a formation. Intracellular mycobacteria have been seen either in close app
 osition to LDs or even “plunging” inside these energy storage organell
 es\, possibly corroborating that the bacteria are able to exploit host lip
 ids for their own metabolism. The mechanism by which the bacteria get acce
 ss to these cytosolic lipid stores is still unknown.\nUsing the Dictyostel
 ium discoideum/Mycobacterium marinum infection system as a model for foamy
  macrophages\, we have found that M. marinum exploits lipids from host lip
 id droplets to build up its own lipid inclusion during infection. Striking
 ly\, the Dictyostelium homologue of perilipin and the murine perilipin 2 s
 urrounded bacteria that had escaped to the cytosol of Dictyostelium or mic
 roglial BV-2 cells\, respectively. In addition\, bacterial growth was inhi
 bited in perilipin knockout cells.\nTo test which lipids are preferentiall
 y transported into the mycobacterium-containing compartment\, we interfere
  with host enzymes involved in triacylglycerol (TAG) synthesis. Interestin
 gly\, the Long Chain Fatty Acid CoA Synthase (LC-FACS) 1\, an enzyme that 
 activates fatty acids and transfers them from endosomes to the cytosol\, i
 s recruited to the mycobacterium-containing compartment. In addition\, dia
 cylglycerol acyltransferase 2 (Dgat2) -GFP decorated LDs were seen cluster
 ing around presumably cytosolic bacteria at late infection stages.\nDictyo
 stelium mutants lacking both Dgat enzymes are unable to generate triacylgl
 ycerols and lipid droplets. Instead\, the exogenous fatty acids are esteri
 fied predominantly into phospholipids\, inducing uncontrolled proliferatio
 ns of the endoplasmic reticulum membrane. Strikingly\, M. marinum is able 
 to exploit this alternative source of host (phospho)lipids resulting in ra
 pid reversal of endoplasmic reticulum-proliferation that disappears from i
 nfected cells early during infection. In addition\, the bacteria build up 
 many more lipid inclusions compared to the wild type. This excessive “fa
 ttening” is not accompanied by a significant change in intracellular gro
 wth and metabolic activity\, and thus provides evidence that the storage o
 f neutral lipids does not necessarily induce dormancy.
LOCATION:AI 1153 https://plan.epfl.ch/?room==AI%201153
STATUS:CONFIRMED
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