–
–
04.04.2022 13:30
Research team from Goethe University discovers the Achilles’ heel of a dangerous hospital germ
A team of scientists from the DFG research group 2251, led by Goethe University, has elucidated the structure of an important enzyme in the metabolism of the hospital germ Acinetobacter baumannii. The enzyme “MtlD” is important for the bacterium to produce the sugar alcohol mannitol, which it uses to protect itself from water loss and dehydration in dry or salty environments such as blood or urine. The structural analysis has revealed weak points at which the enzyme can be inhibited in order to damage the hospital germ. (PNAS, DOI: 10.1073/pnas.2107994119)
FRANKFURT. Every year in Europe, more than 670,000 people contract pathogens resistant to antibiotics and 33,000 die from the diseases they cause. In 2017, the WHO named antibiotic resistance as one of the greatest threats to world health. Germs that are resistant to several antibiotics are particularly feared. Among them, Acinetobacter baumannii stands out, a bacterium that has an extraordinarily high ability to develop multi-drug resistance and, as a “hospital germ”, particularly threatens patients with a weakened immune system. Acinetobacter baumannii is very resistant because it can remain infectious for a long time even in a dry environment and can thus survive on the keyboards of medical devices, ward telephones or lamps. This property also helps the microbe survive on dry human skin or in body fluids such as blood and urine, which contain relatively high concentrations of salts and other solutes.
The scientific team of the DFG research group 2251, led by the Goethe University, has now elucidated a central mechanism with which Acinetobacter baumannii establishes itself in such an adverse environment: Like many bacteria and also plants or fungi, Acinetobacter baumannii is able to produce the sugar alcohol mannitol to produce a substance that binds water very strongly. This prevents Acinetobacter baumannii from drying out.
However, the way in which Acinetobacter baumannii produces mannitol is almost unique: the last two steps in mannitol production are catalyzed by one enzyme complex instead of two, as is the case in most organisms. This enzyme “MtlD” with two catalytic activities was discovered in 2018 by scientists led by Prof. Beate Averhoff and Prof. Volker Müller. The team led by Prof. Klaas Martinus Pos, who is also a member of the DFG research group, has now succeeded in clarifying the spatial structure of the enzyme.
Prof. Pos explains: “We found that the enzyme usually exists in the form of free monomers. Although they have the two necessary catalytic activities, they are inactive. Only a dry or salty environment triggers the so-called osmotic stress in the bacterium, as a result of which the monomers combine to form dimers. Only then does the enzyme become active and produce mannitol.” The scientists also found out which points in the structure are particularly important for the catalytic functions of the enzyme and dimer formation.
Prof. Volker Müller, spokesman for the DFG research group 2251, is convinced: “This work shows an important new starting point for combating this hospital germ. Because we have identified a biochemically sensitive point in the metabolism of the hospital germ. This is where tailor-made substances to inhibit the enzyme could come into play in the future.”
Images for download:
1) Mannitol producing enzyme
https://www.uni-frankfurt.de/116943466
Reminiscent of a butterfly: the mannitol-producing enzyme of the hospital germ Acinetobacter baumannii only protects the bacterium from water loss and dehydration in its dimer form. Image: Klaas Martinus Pos, Goethe University Frankfurt
2) Acinetobacter baumannii
https://commons.wikimedia.org/wiki/File:Acinetobacter_baumannii.JPG
Scanning electron micrograph of a cluster of gram-negative, motile bacteria of the species Acinetobacter baumannii. Photo: Janice Carr
Scientific contacts:
Prof. Dr. Volker Mueller
Spokesman for Research Group 2251
Department of Molecular Microbiology & Bioenergetics
Institute for Molecular Biosciences
Goethe University Frankfurt
Tel: +49 (0)69 798-29507
[email protected]
Prof. Dr. Klaas Martinus Pos
Professorship for membrane transport machines
Institute of Biochemistry
Goethe University Frankfurt
Tel.: +49 (0)69 798-29251
[email protected]
Originalpublikation:
Heng-Keat Tam, Patricia König, Stephanie Himpich, Ngoc Dinh Ngu, Rupert Abele,Volker Müller, Klaas M. Pos: Unidirectional mannitol synthesis of Acinetobacter baumannii MtlD is facilitated by the helix-loop-helix-mediated dimer formation. Proc. Natl. Acad. Sci. U.S.A. (2022) https://www.pnas.org/doi/full/10.1073/pnas.2107994119
Features of this press release:
Journalists, business representatives, scientists
Biology, chemistry, medicine
nationwide
Research results, scientific publications
Deutsch
—
–
