Quantitative analysis of the Brucella suis proteome reveals metabolic adaptation to long-term nutrient starvation

BACKGROUND: During the infection process, bacteria are confronted with various stress factors including nutrient starvation. In an in vitro model, adaptation strategies of nutrient-starved brucellae, which are facultative intracellular pathogens capable of long-term persistence, were determined. RESULTS: Long-term nutrient starvation in a medium devoid of carbon and nitrogen sources resulted in a rapid decline in viability of Brucella suis during the first three weeks, followed by stabilization of the number of viable bacteria for a period of at least three weeks thereafter. A 2D-Difference Gel Electrophoresis (DIGE) approach allowed the characterization of the bacterial proteome under these conditions. A total of 30 proteins showing altered concentrations in comparison with bacteria grown to early stationary phase in rich medium were identified. More than half of the 27 significantly regulated proteins were involved in bacterial metabolism with a marked reduction of the concentrations of enzymes participating in amino acid and nucleic acid biosynthesis. A total of 70% of the significantly regulated proteins showed an increased expression, including proteins involved in the adaptation to harsh conditions, in regulation, and in transport. CONCLUSIONS: The adaptive response of Brucella suis most likely contributes to the long-term survival of the pathogen under starvation conditions, and may play a key role in persistence.