BAM, an attractive target to develop new antibiotics


Click ! Bacteria caught in the act

(UCLouvain Press release)

The resistance of bacteria to antibiotics is a major health problem. The problem ? Bacteria acquire new defense mechanisms to counteract the action of drugs. For several years, the team of Jean-François Collet, professor at the de Duve Institute at UCLouvain, has been interested in this question, and in particular in bacteria surrounded by two membranes (or two surrounding walls).

For a bacterium to survive, it must succeed in building its two surrounding walls and, once assembled, it must protect them from attacks by toxic molecules, including certain antibiotics. Indeed, if one of the walls is damaged, the bacterium dies.

In the outer perimeter wall, there is a particularly important type of guard tower. These towers, called BAM, are essential places for the surveillance, maintenance and protection of fortifications. Several discoveries, including by UCLouvain, have made BAM a prime target for the development of new antibiotics. However, despite the intense work of many university laboratories and pharmaceutical companies, the mode of operation of BAM remains poorly understood, which hinders the development of new antibacterial strategies.

UCLouvain scientists have caught BAM red-handed. The BAM guard towers are compulsory crossing points for all protein soldiers who stand guard on the ramparts as well as for certain protein soldiers who leave the bacterial fortification to patrol the surroundings. The UCLouvain scientists have achieved the feat of obtaining an instantaneous photograph (or three-dimensional structure), which makes it possible to observe BAM in the process of exporting one of the protein soldiers (RcsF) through the outer surrounding wall.

This UCLouvain discovery, published in the prestigious scientific journal Nature Chemical Biology, offers an unprecedented perspective: it provides precious information on the mechanism of bacteria and offers a new angle of attack to take over the BAM watchtowers during antibiotic treatment. In this sense, the discovery of the UCLouvain researchers contributes to the global effort to respond to this growing problem.

This research was conducted by an international team from the de Duve Institute of UCLouvain, in collaboration with researchers from the VUB, VIB, CNRS and the University of Leeds.

Article describing this research

Structural insight into the formation of lipoprotein-β-barrel complexes

Rodríguez-Alonso R, Létoquart J, Nguyen VS, Louis G, Calabrese AN, Iorga BI, Radford SE, Cho SH, Remaut H, Collet JF

Nat. Chem. Biol. (2020) 16(9):1019-1025

In the press - Click... Resistant bacteria caught in the act ! - 22/06/2020 – Des chercheurs belges découvrent comment piéger les bactéries super résistantes – 22/06/2020 – Antibiorésistance : le système de défense des bactéries enfin percé à jour ? – 22/06/2020 – Clic, clac : l'UCLouvain capte l'image d'une protéine-soldat en ordre de bataille – 22/06/2020

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РИА Новости – Биологи нашли "брешь" в обороне бактерий от антибиотиков – 22/06/2020 – Suçüstü Yakalanan Dirençli Bakteriler – 23/06/2020 – Resistente Bakterien auf frischer Tat ertappt! – 24/06/2020

NotiMé – Avances en la batalla contra las bacterias resistentes a los antibióticos – 29/06/2020 – Este descubrimiento podría ser crucial en la lucha contra la resistencia bacteriana – 29/06/2020 – Captan cómo las bacterias se hacen resistentes a antibióticos – 30/06/2020

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The research was funded by the EOS program and WELBIO. The co-first author of the publication, Raquel Rodriguez Alonso, is supported by the European ITN network Train2Target which aims to train a new generation of scientists specializing in the research of new antibiotics.