Precious transition metals: the importance of Zn2+, Mn2+ and Cu2+ in the human pathogen Enterococcus faecalis

Dissertation presented to obtain the Ph.D degree in Biology

Enterococcus faecalis is a commensal bacterium able to colonize different sites in the human host, such as the gastrointestinal tract, the genito-urinary tract and the oral cavity. It can also be found in numerous other environments, including soil, sand, water, food products and plants. These bacteria show a dual behavior: they can behave quite harmlessly as commensals, but are able to become opportunistic pathogens and cause serious infections, such as urinary tract infections and endocarditis, in hospital settings. The question as to how these bacteria are able to change from commensalism to pathogenicity has directed many recent studies to focus on the environmental host conditions that may trigger this transition as well as on the underlying molecular mechanisms. Metals are very important elements in the host environment, as they are key components of many proteins and are involved in numerous cell processes in both the host and the invading pathogen. The maintenance of metal homeostasis is fundamental to both to ensure that metabolism and cell functions are functioning properly. Variations in this homeostasis must be tightly regulated. In several Gram positive pathogens, metal homeostasis and regulation has been linked to their pathogenicity. The lack of knowledge on this subject in E. faecalis motivated the work presented in this thesis.(...)

Apoio financeiro da FCT e do FSE no âmbito do Quadro Comunitário de apoio BD nº SFRH/BD/30362/2006