Research Fellows Directory
Professor Alain Filloux
Imperial College London
Pseudomonas aeruginosa is a human bacterial pathogen, responsible for severe nosocomial infections. These infections are fatal in cystic fibrosis patients.
The persistence of infection is a major cause of morbidity and mortality in the world, and we want to address this problem by using two approaches.
Bacteria can establish chronically by forming biofilms. Biofilm results from bacterial attachment to a surface and production of an extracellular matrix, which will encase the bacterial population. Biofilms are resistant to the immune system and to antibiotic treatments. We showed that cell surface appendages, called fimbriae or Cup, as well as exopolysaccharide, called Pel, are necessary for establishing a biofilm. We identified regulatory components, which respond to environmental signals, and which control assembly of the Cup fimbriae and production of Pel exopolysaccharide. We try to understand how these regulatory cascades work in order to design molecules that could mimic signalling and induce biofilm dispersal. Biofilm disruption will result in a transition to free-swimming bacteria, which will become again accessible to the immune system and to antibiotic treatments.
Other mechanisms involved in Pseudomonas pathogenesis are the so-called protein secretion systems. These systems release enzymes and toxins, which most frequently are involved in host tissue degradation and cytotoxicity. A novel secretion system, type VI secretion system or T6SS, has been identified as being co-regulated with determinants involved in biofilm formation. Moreover, mutants affected in this system are compromised for the development of chronic infections. Three T6SS genetic loci have been identified. Our aim is to understand the molecular mechanisms of the type VI secretion system, to identify and characterize the proteins transported and to understand their role in chronic infection.