Navigation Links
LCSB discovers endogenous antibiotic in the brain
Date:5/6/2013

Luxembourg, 6 May 2013 Scientists from the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have discovered that immune cells in the brain can produce a substance that prevents bacterial growth: namely itaconic acid. Until now, biologists had assumed that only certain fungi produced itaconic acid. A team working with Dr. Karsten Hiller, head of the Metabolomics Group at LCSB, and Dr. Alessandro Michelucci has now shown that even so-called microglial cells in mammals are also capable of producing this acid. "This is a ground breaking result," says Prof. Dr. Rudi Balling, director of LCSB: "It is the first proof of an endogenous antibiotic in the brain." The researchers have now published their results in the prestigious scientific journal PNAS.

Alessandro Michelucci is a cellular biologist, with focus on neurosciences. This is an ideal combination for LCSB with its focus on neurodegenerative diseases, and Parkinson's disease especially i.e. changes in the cells of the human nervous system. "Little is still known about the immune responses of the brain," says Michelucci.

"However, because we suspect there are connections between the immune system and Parkinson's disease, we want to find out what happens in the brain when we trigger an immune response there." For this purpose, Michelucci brought cell cultures of microglial cells, the immune cells in the brain, into contact with specific constituents of bacterial membranes. The microglial cells exhibited a response and produced a cocktail of metabolic products.

This cocktail was subsequently analysed by Karsten Hillers metabolomics group. Upon closer examination, the scientists discovered that production of one substance in particular - itaconic acid - was upregulated. "Itaconic acid plays a central role in the plastics production. Industrial bioreactors use fungi to mass-produce it," says

Hiller: "The realisation that mammalian cells synthesise itaconic acid came as a major surprise."

However, it was not known how mammalian cells can synthesise this compound. Through sequence comparisons of the fungi's enzyme sequence to human protein sequences, Karsten Hiller then identified a human gene, which encodes a protein similar to the one in fungi: immunoresponsive gene 1, or IRG1 for short a most exciting discovery as the function of this gene was not known. Says Hiller: "When it comes to IRG1, there is a lot of uncharted territory. What we did know is that it seems to play some role in the big picture of the immune response, but what exactly that role was, we were not sure."

To change this situation, the team turned off IRG1 in cell cultures and instead added the gene to cells that normally do not express it. The experiments confirmed that in mammals, IRG1 codes for an itaconic acid-producing enzyme. But why? When immune cells like macrophages and microglial cells take up bacteria in order to inactivate them, the intruders are actually able to survive by using a special metabolic pathway called the glyoxylate shunt. According to Hiller, "macrophages produce itaconic acid in an effort to foil this bacterial survival strategy.

The acid blocks the first enzyme in the glyoxylate pathway. Which is how macrophages partially inhibit growth in order to support the innate immune response and digest the bacteria they have taken up." LCSB director Prof. Dr. Rudi Balling describes the possibilities that these insights offer: "Parkinson's disease is highly complex and has many causes. We now intend to study the importance of infections of the nervous system in this respect and whether itaconic acid can play a role in diagnosing and treating Parkinson's disease."


'/>"/>

Contact: karsten.hiller@uni.lu
karsten.hiller@uni.lu
352-466-644-6136
University of Luxembourg
Source:Eurekalert

Related biology news :

1. Team discovers how bacteria resist a Trojan horse antibiotic
2. Study discovers genetic pathway impacting the spread of cancer cells
3. NOAA discovers way to detect low-level exposure to seafood toxin in marine animals
4. New study discovers powerful function of single protein that controls neurotransmission
5. La Jolla Institute scientist discovers key step in immune system-fueled inflammation
6. NUS-led research team discovers how bacteria sense salt stress
7. Team discovers how western corn rootworm resists crop rotation
8. Team discovers reason that male moths can keep finding females
9. Study in mice discovers injection of heat-generating cells reduces belly fat
10. CSHL-led team discovers new way in which plants control flower production
11. International team discovers likely basis of birth defect causing premature skull closure in infants
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/7/2017)...   MedNet Solutions , an innovative SaaS-based eClinical ... research, is pleased to announce that the latest release ... flexible and award winning eClinical solution, is now available ... is a proven Software-as-a-Service (SaaS) clinical research technology platform ... also delivers an entire suite of eClinical tools to ...
(Date:2/3/2017)... 3, 2017  Texas Biomedical Research Institute announced that its ... Schlesinger as the Institute,s new President and CEO. Dr. ... 31, 2017. He is currently the Chair of the Department ... for Microbial Interface Biology at Ohio State University. ... President and CEO of Texas Biomed," said Dr. James ...
(Date:2/2/2017)... Feb. 1, 2017  Central to its deep ... advances worldwide, The Japan Prize Foundation today announced ... have pushed the envelope in their respective fields ... Three scientists are being recognized with the 2017 ... not only contribute to the advancement of science ...
Breaking Biology News(10 mins):
(Date:2/22/2017)... , ... February 22, 2017 , ... ... is has acquired Kendall Research Systems, LLC (KRS) clinical development program. ... develops neural interface technology for research and clinical applications. The terms of the ...
(Date:2/22/2017)... 22, 2017  PrimeVax Immuno-Oncology, Inc. announced today its ... the Annual Biocom Global Life Science Partnering Conference.  The ... AM, at the Torrey Pines Lodge, in San Diego.  ... at Biocom who have chosen our company, amongst numerous ... companies, investors, and clinical researchers," said Mr. Chen. "In ...
(Date:2/22/2017)... (PRWEB) , ... February 22, ... ... Collaborative (TOPEC), the leading medical education provider of women’s health, primary ... by the Accreditation Council for Continuing Medical Education (ACCME). ACCME’s Accreditation with ...
(Date:2/22/2017)... ... February 22, 2017 , ... ... engineers, and scientists from around the world, is pleased to announce the 2nd ... and 23, 2017. This premier, online-only conference focused on the development and advancements ...
Breaking Biology Technology: