Proteomic analysis of Brucella suis under oxygen deficiency reveals flexibility in adaptive expression of various pathways

Abstract

Low oxygen tension was proposed to be one of the environmental parameters characteristic of the patho-physiological conditions of natural infections by Brucella suis. We previously showed that various respiratory pathways may be used by B. suis in response to microaerobiosis and anaerobiosis. Here, we compare the whole proteome of B. suis exposed to such low-oxygenated conditions to that obtained from bacteria grown under ambient air using 2-D DIGE. Data showed that the reduction of basal metabolism was in line with low or absence of growth of B. suis. Under both microaerobiosis and anaerobiosis, glycolysis and denitrification were favored. In addition, fatty acid oxidation and possibly citrate fermentation could also contribute to energy production sufficient for survival under anaerobiosis. When oxygen availability changed and became limiting, basic metabolic processes were still functional and variability of respiratory pathways was observed to a degree unexpected for a strictly aerobic microorganism. This highly flexible respiration probably constitutes an advantage for the survival of Brucella under the restricted oxygenation conditions encountered within host tissue.

TheBrucella abortusPhosphoglycerate Kinase Mutant Is Highly Attenuated and Induces Protection Superior to That of Vaccine Strain 19 in Immunocompromised and Immunocompetent Mice

“…The analysis of the intramacrophagic virulome of Brucella suis showed that low levels of nutrients and oxygen are major features of its replicative niche (19). A recent proteomic study has shown that Brucella adapts to low-oxygen conditions intracellularly by upregulating glycolysis and denitrification (1). Most of the upregulated proteins were involved in energy metabolism, such as transketolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and glycerol-3-phosphate ABC transporter.…”

RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

“…In R. sphaeroides , such analyses revealed that PrrA (RegA) regulates as a “master controller” directly or indirectly ~25% of the genes (Eraso et al, 2008). In the case of B. suis , we demonstrated that under low oxygen tension, the bacteria reduce their basal metabolism as growth decreases or stops and activate glycolysis and denitrification to maintain energy production (Al Dahouk et al, 2009). According to these results, we correctly predicted numerous systems under the control of RegA and potentially needed for persistence, which will contribute to give an insight into the mechanisms enabling B. suis to set up persistence.…”

RegA, the Regulator of the Two-Component System RegB/RegA of Brucella suis, Is a Controller of Both Oxidative Respiration and Denitrification Required for Chronic Infection in Mice

“…In previous studies (10,11,12), we demonstrated that B. suis is able to use various systems to adapt to oxygen-limited conditions, in vitro as well as inside the host organism. The flexibility of this bacterium with respect to oxygen depletion is actually very high since it can grow under low oxygen concentrations (10) and survive under anaerobic denitrifying conditions (13) without repression of basic metabolic activities, as shown by our proteomic analysis (12).…”

“…In previous studies (10,11,12), we demonstrated that B. suis is able to use various systems to adapt to oxygen-limited conditions, in vitro as well as inside the host organism. The flexibility of this bacterium with respect to oxygen depletion is actually very high since it can grow under low oxygen concentrations (10) and survive under anaerobic denitrifying conditions (13) without repression of basic metabolic activities, as shown by our proteomic analysis (12). This was therefore in accordance with an earlier classification of several alphaproteobacteria, which distinguished B. melitensis (14) as a bacterium with an expected facultative/aerobic lifestyle, according to its rank 1 position with respect to the number of predicted highly expressed genes of different energy metabolism pathways, denitrification included.…”