Although only a few bacteria are pathogenic, several millions of people die every year due to an infectious disease and the treatments to deal with them are less suitable day after day. Pathogenic bacteria have certain characteristics that they need, and use, to cause disease. There are two main ways to fight against bacteria. First, we can study virulence factors at a molecular level in order to understand the mechanism involved in the infectious process and imagine a way to block them. Second, we can globalize the approach and find out a medication that is able to kill bacteria. Each approach will be illustrated during the seminar through two examples:

1)  The Botox, Dr. Jekyll or Mister Hyde?

The botulinum neurotoxins (BoNTs or Botox) produced by Clostridium botulinum are among the most potent toxins known to man. Minute quantities cause acute symmetric, descending flaccid paralysis, which may lead to death by respiratory failure. The Centers for Disease Control and Prevention (CDC, Atlanta) has classified BoNT as a potential bio-weapon of Category A (maximum threat), because of its extreme potency and lethality, its ease of production and transport, and the need for prolonged intensive care among affected persons. Despite the high toxicity, numerous and widely-used medical applications have emerged in the last 25 years that utilize the toxin. Injection with BoNT is also one of the most common cosmetic correction procedures now being performed. Although much is now known about the catalytic action of the toxin, we have investigated the details of cell recognition and binding in order to understand how the BoNT gets ready to translocate through the membrane.

2) The putative cell elongation complex, PBP1A - PBP2:

Bacterial cell division and daughter cell formation are complex mechanisms whose details are orchestrated by at least a dozen different proteins. Penicillin-binding proteins (PBPs), membrane-associated macromolecules which play key roles in the cell wall synthesis process, have been exploited for over 70 years as the targets of the highly successful β-lactam antibiotics. The increasing incidence of β-lactam resistant microorganisms, coupled to progress made in microbiology, have encouraged the intensive study of PBPs from a variety of bacterial species. In addition, the recent determination of high-resolution structures of PBPs from pathogenic organisms has shed light on the complex intertwining of drug resistance and cell division processes. Due to the challenge to find out a new way to counter the antibiotic resistance we decided to work on the identification of new promising targets. To achieve that goal we focus our efforts on a new putative elongation complex that could be a highly attractive target for the development of novel antibiotherapies.