Brucella spp. are Gram-negative bacteria that infect animals and humans. B. abortus, B. melitensis, and B. suis are major pathogens of cattle, goats and sheep, and swine, respectively. Brucella infections in these food animals have significant economic impacts in areas of the world where they are not controlled by effective eradication programs. In their main animal hosts, brucellosis causes spontaneous abortion or birth of weak offspring, reduced milk production and infertility. Transmission occurs by direct contact with infected blood, placentas, fetuses and consumption of raw animal products, especially milk and milk products (Nicoletti 1989). Understanding the physiology of these bacteria and how host infection is modulated is therefore important for control of these pathogens.
Bacteria manage changes to their environment, such as the stress of host infection, by altering the levels of RNA, protein and signaling molecules to cope with these changes. Proteases play central roles in bacterial physiology. They modulate the activity of cellular proteins and remove damaged proteins from cells. Because proteolysis is irreversible the catalytic function of cellular proteases must be tightly regulated. While the extent and capacity of proteolytic control in Brucella is unknown, modern proteomic strategies have now made it possible to capture this important facet of bacterial regulation.
In this proposal we aim to chart the dynamic proteome in Brucella abortus, identify the roles of specific regulators in controlling these dynamics, and share these results with the scientific community by making a searchable open-access databases. We believe that this atlas will provide a starting point for all those studying Brucella to either identify new candidates of interest or to validate regulatory mechanisms for targets under study. Given the economic and agriculture impact of brucellosis on animal hosts, we predict that this insight will spur understanding of how to manage Brucella infections and reduce the economic burden of this disease.