With the appearance of an ever-increasing number of antibiotic-resistant bacterial strains, the search for new targets in order to address the problem once and for all, is a priority in terms of public health. At ULg’s Protein Engineering Centre, Mohammed Terrak and his team have revealed the role of a series of “protein motifs” of an enzyme that is crucial in the formation of the bacterial wall. This discovery opens new avenues for research into antibacterial molecules.

The ever-widening use of antibiotics to treat diseases of bacterial origin encourages the phenomenon of resistance to these microorganisms. And while all living species are characterised by their ability to adapt to their environment, bacteria excel in this domain (read Antibiotics Against Bacteria). As they multiply, bacteria mutate and some acquire the genetic weapons necessary to resist the products that are designed to destroy them. The mutant bacteria are then selected since they are the only ones to survive the treatment. Furthermore, these “specially-selected” bacteria can transmit their power of resistance by transferring their genetic material to their fellow kind. Following the dissemination of these resistant genes, traditional treatments rapidly become ineffective in curing diseases caused by these bacteria. Hence the interest of searching for the new “Achilles Tendons” of these microscopic beings.

The bacterial wall is not an infallible armour

One of the particularities of the majority of bacteria is that they are equipped with a characteristic cell wall which is not found in Eukaryotes. “This fundamental difference is a godsend in terms of the fight against these microbes because by aiming to destroy the wall of these bacteria, the antibiotics have no risk of harming the patients”, points out Mohammed Terrak, qualified FNRS researcher at ULg’s Protein Engineering Centre. Considering this particular characteristic, scientists therefore decided to examine antibiotics whose mechanism of action would prevent the formation of this famous armour.

The bacterial wall is composed of long chains of sugars linked to each other by peptides to form a rigid three-dimensional network, like a sort of bag which surrounds and protects the microorganism. Without this protection, and under the effect of the osmotic pressure which reigns inside its cytoplasm, the bacterium bursts.

Once synthesised inside the bacterium, the precursors required for the construction of the wall cross the plasma membrane. They are then taken charge of by a protein with a dual mission: to create the long chains of sugar and assemble them in a network, activities which are respectively known as glycosyltransferase et transpeptidase.