Evaluation of the Effects of Erythritol on Gene Expression in Brucella abortus

Rodrı́guez, Marı́a C.; Viadas, Cristina; Seoane, Asunción; Sangari, Félix J.; López-Goñi, Ignacio; Garcı́a-Lobo, Juan M.

doi:10.1371/journal.pone.0050876

Cited by 27 publications

(19 citation statements)

References 43 publications

(48 reference statements)

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“…RNA-seq does not require probe sequences and has a greater dynamic range for measuring very low or very high gene expression levels (Croucher and Thomson, 2010). The power of RNA-seq has been demonstrated in the transcriptomics studies of Brucella (Wang et al, 2011;Rodriguez et al, 2012) and many other bacteria (Croucher and Thomson, 2010;Pinto et al, 2011). Therefore, we used RNA-seq to provide fundamental gene-level evidence and detailed gene expression profiles regulated by CspA in Brucella.…”

Section: Introductionmentioning

confidence: 99%

RNA-seq reveals the critical role of CspA in regulating Brucella melitensis metabolism and virulence

Wang

Liu

et al. 2016

Sci. China Life Sci.

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Brucella melitensis is a facultative intracellular bacterium that replicates within macrophages. The ability of Brucella to survive and multiply in the hostile environment of host macrophages is essential for its virulence. The cold shock protein CspA plays an important role in the virulence of B. melitensis. To analyze the genes regulated by CspA, the whole transcriptomes of B. melitensis NI∆cspA and its parental wild-type strain, B. melitensis NI, were sequenced and analyzed using the Solexa/Illumina sequencing platform. A total of 446 differentially expressed genes were identified, including 324 up-regulated and 122 down-regulated genes. Numerous genes identified are involved in amino acid, fatty acid, nitrogen, and energy metabolism. Interestingly, all genes involved in the type IV secretion system and LuxR-type regulatory protein VjbR were significantly down-regulated in NIcspA. In addition, an effector translocation assay confirmed that the function of T4SS in NI∆cspA is influenced by deletion of the cspA gene. These results revealed the differential phenomena associated with virulence and metabolism in NI∆cspA and NI, providing important information for understanding detailed CspA-regulated interaction networks and Brucella pathogenesis. Brucella melitensis, cold shock protein, transcriptome, virulence Citation:Wang, Z., Liu, W., Wu, T., Bie, P., and Wu, Q. (2016). RNA-seq reveals the critical role of CspA in regulating Brucella melitensis metabolism and virulence. Sci China Life Sci, 59, 417 -424.

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Section: Introductionmentioning

confidence: 99%

RNA-seq reveals the critical role of CspA in regulating Brucella melitensis metabolism and virulence

Wang

Liu

et al. 2016

Sci. China Life Sci.

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“…RNA-seq does not require probe sequences and also has a greater dynamic range for measuring very low or very high gene expression levels 21 . The power of RNA-seq has been demonstrated in the transcriptomics studies for Brucella 22 23 24 and many other bacteria 19 20 21 . Therefore, we used RNA-seq in current study.…”

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confidence: 99%

RNA-seq reveals the critical role of OtpR in regulating Brucella melitensis metabolism and virulence under acidic stress

Liu

Dong

et al. 2015

Sci Rep

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The response regulator OtpR is critical for the growth, morphology and virulence of Brucella melitensis. Compared to its wild type strain 16 M, B. melitensis 16 MΔotpR mutant has decreased tolerance to acid stress. To analyze the genes regulated by OtpR under acid stress, we performed RNA-seq whole transcriptome analysis of 16 MΔotpR and 16 M. In total, 501 differentially expressed genes were identified, including 390 down-regulated and 111 up-regulated genes. Among these genes, 209 were associated with bacterial metabolism, including 54 genes involving carbohydrate metabolism, 13 genes associated with nitrogen metabolism, and seven genes associated with iron metabolism. The 16 MΔotpR also decreased capacity to utilize different carbon sources and to tolerate iron limitation in culture experiments. Notably, OtpR regulated many Brucella virulence factors essential for B. melitensis intracellular survival. For instance, the virB operon encoding type IV secretion system was significantly down-regulated, and 36 known transcriptional regulators (e.g., vjbR and blxR) were differentially expressed in 16 MΔotpR. Selected RNA-seq results were experimentally confirmed by RT-PCR and RT-qPCR. Overall, these results deciphered differential phenomena associated with virulence, environmental stresses and cell morphology in 16 MΔotpR and 16 M, which provided important information for understanding the detailed OtpR-regulated interaction networks and Brucella pathogenesis.

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“…(B) D-erythrose-4-P is further processed by enzymes of the pentose phosphate pathway to generate fructose-6-P and glyceraldehyde-3-P, two intermediates of glycolysis/gluconeogenesis (C). The proteins whose genes are induced by erythritol (9) are circled in red. The new proposed gene names are indicated in parentheses below the old designations.…”

Section: Resultsmentioning

confidence: 99%

“…The gene encoding the putative regulatory protein DeoR, which precedes tpiA2 on the chromosome, has been designated eryR by Geddes and colleagues (13). Expression of these genes, including eryA,B,C,D, is induced in the presence of erythritol (9,12). This regulation is partly based on the release by erythritol of the EryD-dependent repression of eryA,B,C,D expression (12), whereas the role of EryR remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, this four-carbon polyol is a preferential carbon source of Brucella, promotes growth, and up-regulates the expression of major virulence factors and key enzymes of central metabolism (5)(6)(7)(8)(9). In vivo, it has been observed that parenteral injections of erythritol increase the numbers of Brucella in the spleens of intraperitoneally infected calves (3,7).…”

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Erythritol feeds the pentose phosphate pathway via three new isomerases leading to D-erythrose-4-phosphate in Brucella

Barbier

Collard

Zúñiga-Ripa

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Erythritol is an important nutrient for several α-2 Proteobacteria, including N 2-fixing plant endosymbionts and Brucella, a worldwide pathogen that finds this four-carbon polyol in genital tissues. Erythritol metabolism involves phosphorylation to L-erythritol-4-phosphate by the kinase EryA and oxidation of the latter to L-3-tetrulose 4-phosphate by the dehydrogenase EryB. It is accepted that further steps involve oxidation by the putative dehydrogenase EryC and subsequent decarboxylation to yield triose-phosphates. Accordingly, growth on erythritol as the sole C source should require aldolase and fructose-1,6-bisphosphatase to produce essential hexose-6-monophosphate. However, we observed that a mutant devoid of fructose-1,6-bisphosphatases grew normally on erythritol and that EryC, which was assumed to be a dehydrogenase, actually belongs to the xylose isomerase superfamily. Moreover, we found that TpiA2 and RpiB, distant homologs of triose phosphate isomerase and ribose 5-phosphate isomerase B, were necessary, as previously shown for Rhizobium. By using purified recombinant enzymes, we demonstrated that L-3-tetrulose-4-phosphate was converted to D-erythrose 4-phosphate through three previously unknown isomerization reactions catalyzed by EryC (tetrulose-4-phosphate racemase), TpiA2 (D-3-tetrulose-4-phosphate isomerase; renamed EryH), and RpiB (D-erythrose-4-phosphate isomerase; renamed EryI), a pathway fully consistent with the isotopomer distribution of the erythrose-4-phosphate-derived amino acids phenylalanine and tyrosine obtained from bacteria grown on 13 C-labeled erythritol. D-Erythrose-4-phosphate is then converted by enzymes of the pentose phosphate pathway to glyceraldehyde 3-phosphate and fructose 6-phosphate, thus bypassing fructose-1,6-bisphosphatase. This is the first description to our knowledge of a route feeding carbohydrate metabolism exclusively via D-erythrose 4-phosphate, a pathway that may provide clues to the preferential metabolism of erythritol by Brucella and its role in pathogenicity.rucellosis is a widespread bacterial zoonosis caused by the facultative intracellular pathogens Brucella spp. Domestic ruminants and swine, which altogether represent more than 4 billion animals worldwide, are highly susceptible, and in this livestock, the brucellae characteristically target the genital organs and cause abortion and infertility (1). Close to parturition, these bacteria reach exceedingly high numbers (up to 10 14 bacteria per conceptus) (2), thus making brucellosis abortion a highly contagious condition.It is accepted that this tropism and extensive multiplication relate to the high erythritol concentration in the genital organs of those animals (3, 4). In vitro, this four-carbon polyol is a preferential carbon source of Brucella, promotes growth, and up-regulates the expression of major virulence factors and key enzymes of central metabolism (5-9). In vivo, it has been observed that parenteral injections of erythritol increase the numbers of Brucella in the spleens of intraperitoneally...

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Evaluation of the Effects of Erythritol on Gene Expression in Brucella abortus

Cited by 27 publications

References 43 publications

RNA-seq reveals the critical role of CspA in regulating Brucella melitensis metabolism and virulence

RNA-seq reveals the critical role of CspA in regulating Brucella melitensis metabolism and virulence

RNA-seq reveals the critical role of OtpR in regulating Brucella melitensis metabolism and virulence under acidic stress

Erythritol feeds the pentose phosphate pathway via three new isomerases leading to D-erythrose-4-phosphate in Brucella

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