Tuberculosis, or TB, is a dreaded contagious disease of the lungs and other organs. The causative agent, Mycobacterium tuberculosis (or M. tuberculosis), infects roughly a third of the world's population and one-in-ten to one-in-twenty of the infected population becomes sick or infectious at some point during their lifetime.
The mycobacteria survive, and even thrive, inside host macrophages – cells that are part of the human immune system and that usually engulf and destroy bacteria in structures called phagosomes. M. tuberculosis is taken into phagosomes but it somehow blocks phagosome maturation, and hence survives. Figuring out how could open up new therapeutic targets for the treatment of TB as well as shedding light on the mechanism of intracellular parasitism.
Researchers at the Pasteur Institutes in Seoul and Paris and Institute of Pharmacology and Structural Biology (IPBS) in Toulouse joined forces to systematically search for mycobacterial genes that block phagosome maturation. To do this, they generated 11,000 different mutants of the M. tuberculosis Beijing strain, which has been associated with large outbreaks of TB, increased virulence, and multidrug resistance.
Using a high-throughput visual assay, the researchers screened for mutant mycobacteria that had lost the ability to arrest phagosomal maturation. Lead author Dr. Priscille Brodin, heading the Inserm Avenir Unit at Institut Pasteur Korea describes the screen as "enabling stringent selection of mutants that have the most pronounced subcellular localization within intracellular acidic compartments through the use of automated confocal quantitative imaging. Our approach", she adds, "may be useful to identify virulence genes in other intracellular pathogens".
The team identified ten distinct mutants, only one of which had previously been shown to play a part in phagosome maturation arrest. Finding that two independent mutants mapped to the same region, they studied this locus in more detail. The work revealed that the biosynthesis of particular glycolipids containing acyltrehalose was perturbed, suggesting to the researchers that these glycolipids play a critical role in the early intracellular protection of mycobacteria.
"Our study unravels the role of novel lipid molecules in mycobacterial intracellular parasitism" says Dr. Olivier Neyrolles leading a CNRS Unit at IPBS in Toulouse France. "This establishes potential new drug targets", especially important given the emergence of multidrug-resistant and extensively drug-resistant TB. "In addition", Dr Brodin points out, "the assay that have we developed can be readily adapted for the screening of novel antimicrobials".
1. P. Brodin1, Y. Poquet et al., "High content phenotypic cell-based visual screen identifies Mycobacterium tuberculosis acyltrehalose-containing glycolipids involved in phagosome remodeling", PLoS Pathogens, finish reference…
Jean Kim | EurekAlert!
Molecular libraries for organic light-emitting diodes
24.04.2017 | Goethe-Universität Frankfurt am Main
Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Life Sciences
24.04.2017 | Earth Sciences
24.04.2017 | Machine Engineering