Since their introduction on the international market in the 1930s, β-lactam-type antibiotics such as penicillin and cephalosporin have been the treatment of choice for infections ranging from pneumonia to bubonic plague. These β-lactams disrupt the bacterial cell wall-forming machinery. To achieve this, they block the activity of penicillin-binding proteins (PBPs), which catalyze the last steps in the synthesis of peptidoglycan, an essential wall component. During the synthesis of this component, PBPs participate in the various stages of the cell cycle, in particular the division of the bacterium and its prior elongation. This explains why a number of PBPs are essential for bacterial survival.
Researchers from the IBS have taken an interest in MreC, a bacterial cytoskeleton protein that serves as an "anchor" for other members of the elongation complex. The researchers have characterized, for the first time, the complex between a PBP and MreC. The PBP2:MreC complex thus represents the structural 'core' of the elongation. Any interference with its formation, for example by the introduction of mutations, prevents proper wall formation during elongation of the daughter cells, generating cells with an aberrant diameter that eventually die. The interaction surface between the two proteins represents a potential target for the development of specific inhibitors. Thus, this work paves the way for a new type of antibiotic, which does not block PBP activity like β-lactams do, but which prevents the formation of the PBP2:MreC complex.