CLUSTER 4: Public health
Biofilms are central to all microbially-induced diseases and may become chronic. Important hallmarks of biofilm infections include extreme tolerance to the action of conventional antimicrobial agents and an almost infinite capacity to evade host defense systems, in particular innate immunity. This is strikingly similar to the behaviour of environmental biofilms that allow bacteria to resist a multitude of environmental stresses including predation. Another obvious commonality between chronic infections and pathogens in environmental and engineering bioprocess settings is that traditional methods for detection and enumeration greatly underestimate their actual presence because they live in the "concealed" biofilm state. Unravelling mechanisms bacteria use to survive encounters with environmental predators and "host organism predators" (e.g. the cellular immune system) enables us to understand how primary, as well as how opportunistic pathogens can be concealed and how they survive and disseminate from the environment to humans.
One of the key environmental factors for improved health the quality of drinking water. For example, concealed bacteria (those associated with algae, phytoplankton or internalised in amoebae) in drinking water supplies in combination with host susceptibility may spark biofilm infections that can lead to chronic diseases.
SCELSE Cluster 4 research involves characterisation of phagocytosis resistance of environmental pathogens including the role of biofilm formation, development of protective shielding, and internalisation, by means of a variety of experimental methods, including mixed biofilm-amoeba/white blood cell model systems in vitro and in vivo rodent models. As for all analyses of complex microbial communities at SCELSE, the toolbox and capacity of Clusters 2 and 3 will be employed for a comprehensive description of community composition and function. Consequently, Cluster 4 will employ a thorough understanding of how biofilms provide a basis for pathogens to develop resistance, and how this explains their presence in drinking water biofilms as well as in biofilm mediated chronic infection and inflammation conditions. In parallel, Cluster 4 will develop a chemical biology approach to target and control the biofilm resistance traits.
With a focus on biofilm controlling chemistry, SCELSE will become a front-runner in developing novel antibiofilm drugs that will mitigate the negative impact of biofilms by restoring proper action of environmental predators and the immune system.
|High density Enterococcus faecalis infection within the kidney of diabetic mice during experimental urinary tract infection.||Electron micrograph of immuno-gold labeled proteins in E. faecalis showing co-localisation of secretion and cell-wall sorting.||Uropathogenic E. coli (green) intracellular biofilm-like community within bladder epithelial cells (red) during in vivo murine experimental urinary tract infection.||Drinking water quality - a key environmental factor for improved health.|