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Review Article

Brucella central carbon metabolism: an update

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Pages 182-211 | Received 04 Nov 2016, Accepted 16 May 2017, Published online: 12 Jun 2017
 

Abstract

The brucellae are facultative intracellular pathogens causing brucellosis, an important zoonosis. Here, we review the nutritional, genetic, proteomic and transcriptomic studies on Brucella carbon uptake and central metabolism, information that is needed for a better understanding of Brucella virulence. There is no uniform picture across species but the studies suggest primary and/or secondary transporters for unknown carbohydrates, lactate, glycerol phosphate, erythritol, xylose, ribose, glucose and glucose/galactose, and routes for their incorporation to central metabolism, including an erythritol pathway feeding the pentose phosphate cycle. Significantly, all brucellae lack phosphoenolpyruvate synthase and phosphofructokinase genes, which confirms previous evidence on glycolysis absence, but carry all Entner–Doudoroff (ED) pathway and Krebs cycle (and glyoxylate pathway) genes. However, glucose catabolism proceeds through the pentose phosphate cycle in the classical species, and the ED pathway operates in some rodent-associated brucellae, suggesting an ancestral character for this pathway in this group. Gluconeogenesis is functional but does not rely exclusively on classical fructose bisphosphatases. Evidence obtained using infection models is fragmentary but suggests the combined or sequential use of hexoses/pentoses, amino acids and gluconeogenic substrates. We also discuss the role of the phosphotransferase system, stringent reponse, quorum sensing, BvrR/S and sRNAs in metabolism control, an essential aspect of the life style of facultative intracellular parasites.

Notes

Disclosure statement

The authors report no declarations of interest.

Notes

1 The Brucella OMPs are categorized according to their molecular weight. Group 1 have an approximate molecular mass of 94 kDa, group 2 are approximately 41 to 43 kDa, and group 3 have an approximate molecular mass of 28–30 kDa (Verstreate et al. Citation1982).

2 The primary structure of the nucleotide binding domain of the CUT2 family appears to be a “natural” fusion of two ABC domains (Schneider Citation2001).

3 Gerhardt's Brucella “minimal” (defined) medium consists of 0.5% lactate, 0.15% glutamate, 3% glycerol, vitamins and mineral salts. Although described as “minimal” medium, not all Brucella strains require the three carbon substrates simultaneously. Of the strains included in this review, at least B. abortus 2308 can grow on any combination of two of the substrates in this medium (Zuñiga-Ripa et al., 2014). Another commonly used defined medium is Plommet's medium, which contains 0.15% glucose, vitamins and mineral salts (including ammoniun). On the other hand, many authors describe as “minimal” media, media that are supplemented with various concentrations of yeast extract. Common complex media are tryptic soy broth (0.25% glucose, approximately 0.4% casein-soya peptones) and 2YT (10% yeast extract, 1% tryptone).

4 The first reaction transfers two electrons on a quinone of the respiratory chain, the second reaction transfers two electrons to NAD+.

5 At least in our hands, B. abortus 2308 and B. melitensis 16M do not grow in Plommet's medium where glucose is added as the sole carbon source (see endnote 3). For strain 16M, this seems related to a requirement for methionin rather than to an inability to use glucose.

6 “Tn-seq refers to a range of transposon insertion sequencing techniques that use a random transposon mutant library and high-throughput sequencing to study fitness of mutant strains and/or to identify genes that are essential or advantageous for growth under a specific set of conditions (Solaimanpour et al. Citation2015).

Additional information

Funding

This work was supported Fonds National de la Recherche Scientifique (FNRS) [Convention No. n° 2.4521.10. FRSM-FNRS] and by the Interuniversity Attraction Poles Programme (IAP) Phase VII/2012-2017 initiated by the Belgian Science Policy Office [Project P7/28].

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