Science

Baltic amber to fight drug-resistant infections?

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This pretty honey-colored resin is not only used in jewelry. For centuries, it has been attributed medicinal properties. Even today, babies are given amber necklaces to prevent toothache, and some people use it for respiratory tract infections. Popular belief or reality? Scientists have identified compounds that could explain the therapeutic effects of Baltic amber. This discovery could also lead to the development of new drugs to overcome antibiotic resistance.

Antibiotic resistance, or antibiotic resistance, refers to the fact that antibiotic treatment is no longer effective on a bacterial infection. It has developed gradually, over the years, through inappropriate and excessive use of antibiotics, which has led to pressure to select pathogenic bacteria, favoring the appearance of increasingly resistant strains. In 2015, there were more than 670,000 infections with bacteria resistant to antibiotics in Europe. It is now a major public health issue.

According to the Centers for Disease Control and Prevention, in the United States, at least 2.8 million people contract infections resistant to antibiotics, resulting in 35,000 deaths. While visiting her family in Lithuania, Elizabeth Ambrose, a pharmacology researcher at the University of Minnesota, collected amber samples and took a keen interest in the medicinal uses of this fossilized resin.

Resin acids known for their biological role

Baltic amber, also known as succinite, results from the fossilization of plant resin from conifers from the Eocene era, around 44 million years ago. The largest deposits of amber are found on the shores of the Baltic Sea; 90% of world production comes from the Iantarny mine, in the Russian exclave of Kaliningrad.

Resin was dripping from the now extinct pine trees of the Sciadopityaceae and acted as a defense against microorganisms such as bacteria and fungi, as well as herbivorous insects, many of which were trapped in the resin. ” We knew from previous research that there were substances in Baltic amber that could lead to new antibiotics, but they had not been systematically explored. ”Says Elizabeth Ambrose.

She and her team therefore set out to extract the various compounds present in this resin from the paleogene. They looked at samples collected by Ambrose, as well as commercially available Baltic amber. ” One of the major challenges was to prepare a fine and homogeneous powder from the amber pebbles, to be able to perform solvent extraction. Says Connor McDermott, who participated in the study. This done, the amber powder was finally analyzed by gas chromatography coupled with mass spectrometry (GC-MS).

The GC-MS spectra obtained made it possible to identify dozens of compounds. The most interesting were abietic acid, dehydroabietic acid, and palustriic acid – metabolites found in plant resins, particularly pine resin. They are organic compounds with 20 carbon atoms, with three rings, whose biological activity is well known: they act as natural wood preservatives.

These acids are however difficult to purify; the researchers therefore bought a small quantity of these acids in their pure form, then entrusted them to a biological analysis laboratory in order to test their activity against several bacterial species, some of which are now resistant to traditional antibiotics.

Reproduce a substance dating from the Eocene

They thus discovered that the compounds extracted from amber showed activity against Gram-positive bacteria, such as certain strains of Staphylococcus aureus (or Staphylococcus aureus), an extremely pathogenic species. On the other hand, they had no action against Gram-negative bacteria.

However, Gram-positive bacteria have a less complex cell wall than Gram-negative bacteria: they have a unimembrane structure, in other words, they have no outer membrane; thus, although very thick, the layer of peptidoglycan composing the cell wall is in direct contact with the external environment. Why is this difference in the behavior of resin acids in relation to these two types of bacteria interesting? ” This implies that the composition of the bacterial membrane is important for the activity of the compounds. McDermott explains.

At the same time, the team examined a sample of Japanese stone pine, the closest living species today to the trees that produced the resin during the Eocene epoch. The researchers extracted the resin from the needles and stems of this tree; they then identified sclarene, a molecule also with 20 carbon atoms, which could theoretically undergo chemical transformations in order to synthesize the bioactive compounds found in the samples of Baltic amber. This constitutes a new avenue towards the mass production of new types of drugs. ” Abietic acids and their derivatives are potentially an untapped source of new drugs, especially for treating infections caused by Gram-positive bacteria, which are increasingly resistant to known antibiotics. Ambrose rejoices.

American Chemical Society

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