The unit of "Pathogenesis of Systemic Infections" at the medical school Necker-Enfants Malades is devoted to the understanding of the mechanisms responsible for diseases linked to systemic dissemination of bacterial pathogens. Systemic infections are responsible for most of the mortality due to bacteria. In developed countries, these infections are often nosocomial and the pathogens resistant to antibiotics. By understanding the pathogenesis of these infections, we aim at designing new diagnostic tools as well as new therapeutic and prophylactic approaches for the treatment of these infections.
To disseminate from their port-of-entry bacteria have developed two main strategies. The first one is used by the " intra-cellular pathogens " (Listeria, Mycobacterium, Brucella, Legionella, Salmonella, Francisella, …). These pathogens use a vehicle, mostly a macrophage, to disseminate, thus implying that the bacteria have developed a strategy allowing survival inside these phagocytic cells The second one is used by the "extra-cellular pathogens" which are the main cause of systemic infections in developed countries,. The bacteria are either Gram negative pathogens (Neisseria, Escherichia coli, Klebsiella, Pseudomonas) or Gram positive (Streptococcus pneumoniae, Streptococcus sp, Staphylococcus, Enterococcus). These extra-cellular pathogens are mostly commensal, and in some circumstances disseminate, survive in the extracellular fluid and resist phagocytosis by polymorphonuclear.
Some of these bacterial pathogens once in the bloodstream will have the ability to cross cellular barriers. One of the tightest barrier in the body is the blood brain barrier (BBB). Among invasive bacterial pathogens, few are capable of invading the brain, thus suggesting that they have developed specific attributes capable to circumvent the BBB. Understanding how these pathogens are capable of invading the brain may help to circumvent the blood brain barrier and design new avenues for the delivery of therapeutic to the brain.
Our goal is to address the mechanisms by which a bacterial pathogen stop being a commensal, disseminate into the bloodstream from its port-of-entry, and eventually cross the BBB