Mycobacterium marinum Degrades Both Triacylglycerols and Phospholipids from Its Dictyostelium Host to Synthesise Its Own Triacylglycerols and Generate Lipid Inclusions

PLoS Pathog. 2017 Jan 19;13(1):e1006095. doi: 10.1371/journal.ppat.1006095. eCollection 2017 Jan.

Abstract

During a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (FAs) and sterols are the major energy and carbon source for Mycobacterium tuberculosis. Mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. Lipid droplets (LDs) store FAs in form of triacylglycerols (TAGs) and are energy reservoirs of prokaryotes and eukaryotes. Using the Dictyostelium discoideum/Mycobacterium marinum infection model we showed that M. marinum accesses host LDs to build up its own intracytosolic lipid inclusions (ILIs). Here, we show that host LDs aggregate at regions of the bacteria that become exposed to the cytosol, and appear to coalesce on their hydrophobic surface leading to a transfer of diacylglycerol O-acyltransferase 2 (Dgat2)-GFP onto the bacteria. Dictyostelium knockout mutants for both Dgat enzymes are unable to generate LDs. Instead, the excess of exogenous FAs is esterified predominantly into phospholipids, inducing uncontrolled proliferation of the endoplasmic reticulum (ER). Strikingly, in absence of host LDs, M. marinum alternatively exploits these phospholipids, resulting in rapid reversal of ER-proliferation. In addition, the bacteria are unable to restrict their acquisition of lipids from the dgat1&2 double knockout leading to vast accumulation of ILIs. Recent data indicate that the presence of ILIs is one of the characteristics of dormant mycobacteria. During Dictyostelium infection, ILI formation in M. marinum is not accompanied by a significant change in intracellular growth and a reduction in metabolic activity, thus providing evidence that storage of neutral lipids does not necessarily induce dormancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, Thin Layer
  • Dictyostelium / metabolism
  • Dictyostelium / microbiology*
  • Fluorescent Antibody Technique
  • Host-Pathogen Interactions / physiology*
  • Inclusion Bodies / metabolism
  • Microscopy, Electron, Transmission
  • Mycobacterium Infections, Nontuberculous / metabolism*
  • Mycobacterium marinum / metabolism*
  • Phospholipids / metabolism
  • Triglycerides / metabolism

Substances

  • Phospholipids
  • Triglycerides

Supplementary concepts

  • Infection with Mycobacterium marinum

Grant support

The work was supported by the grant N° 310030_149390 from the Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (http://www.snf.ch). The funding was received by TS. "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."