Identification of the Operon for the Sorbitol (Glucitol) Phosphoenolpyruvate:Sugar Phosphotransferase System in
            <i>Streptococcus mutans</i>

Boyd, David A.; Thevenot, Tracy; Gumbmann, Markus; Honeyman, Allen L.; Hamilton, Ian R.

doi:10.1128/iai.68.2.925-930.2000

Cited by 29 publications

(21 citation statements)

References 34 publications

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“…Another DeoR-type transcription regulator, SrlR, containing PRDs and EIIB Gat -and EIIA Mtl/Fru -like domains has been described for S. mutans. SrlR controls the expression of the srlDRMAEB operon (78). Besides the putative transcription activator, the operon encodes a glucitol (sorbitol)-specific PTS (srlAEB) and a glucitol-6-P dehydrogenase (srlD).…”

Section: Mtlmentioning

confidence: 99%

How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria

Deutscher

Francke

Postma

2006

Microbiol Mol Biol Rev

1,189

769

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SUMMARY The phosphoenolpyruvate(PEP):carbohydrate phosphotransferase system (PTS) is found only in bacteria, where it catalyzes the transport and phosphorylation of numerous monosaccharides, disaccharides, amino sugars, polyols, and other sugar derivatives. To carry out its catalytic function in sugar transport and phosphorylation, the PTS uses PEP as an energy source and phosphoryl donor. The phosphoryl group of PEP is usually transferred via four distinct proteins (domains) to the transported sugar bound to the respective membrane component(s) (EIIC and EIID) of the PTS. The organization of the PTS as a four-step phosphoryl transfer system, in which all P derivatives exhibit similar energy (phosphorylation occurs at histidyl or cysteyl residues), is surprising, as a single protein (or domain) coupling energy transfer and sugar phosphorylation would be sufficient for PTS function. A possible explanation for the complexity of the PTS was provided by the discovery that the PTS also carries out numerous regulatory functions. Depending on their phosphorylation state, the four proteins (domains) forming the PTS phosphorylation cascade (EI, HPr, EIIA, and EIIB) can phosphorylate or interact with numerous non-PTS proteins and thereby regulate their activity. In addition, in certain bacteria, one of the PTS components (HPr) is phosphorylated by ATP at a seryl residue, which increases the complexity of PTS-mediated regulation. In this review, we try to summarize the known protein phosphorylation-related regulatory functions of the PTS. As we shall see, the PTS regulation network not only controls carbohydrate uptake and metabolism but also interferes with the utilization of nitrogen and phosphorus and the virulence of certain pathogens.

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Section: Mtlmentioning

confidence: 99%

How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria

Deutscher

Francke

Postma

2006

Microbiol Mol Biol Rev

1,189

769

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“…1), of which six have been assigned a role or putative function. Genome analysis reveals a similar organization in other bacteria, including several gram-positive organisms (5,30), with homologues of the transport/metabolic genes (gutAEBD) and the transcriptional activator gene (gutM) being highly conserved. However, GutQ has a narrow phylogenetic distribution confined to a subset of enterobacteria thus far limited to the sequenced gut operons in Escherichia, Shigella, and Salmonella species and Erwinia amylovora (1).…”

Section: Discussionmentioning

confidence: 99%

Identification of GutQ from Escherichia coli as a d -Arabinose 5-Phosphate Isomerase

Meredith¹,

Woodard

2005

J Bacteriol

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The glucitol operon (gutAEBDMRQ) of Escherichia coli encodes a phosphoenolpyruvate:sugar phosphotransferase system that metabolizes the hexitol D-glucitol (sorbitol). The functions for all but the last gene, gutQ, have been previously assigned. The high sequence similarity between GutQ and KdsD, a D-arabinose 5-phosphate isomerase (API) from the 3-deoxy-D-manno-octulosonate (KDO)-lipopolysaccharide (LPS) biosynthetic pathway, suggested a putative activity, but its role within the context of the gut operon remained unclear. Accordingly, the enzyme was cloned, overexpressed, and characterized. Recombinant GutQ was shown to indeed be a second copy of API from the E. coli K-12 genome with biochemical properties similar to those of KdsD, catalyzing the reversible aldol-ketol isomerization between D-ribulose 5-phosphate (Ru5P) and Darabinose 5-phosphate (A5P). Genomic disruptions of each API gene were constructed in E. coli K-12. TCM11[(⌬kdsD)] was capable of sustaining essential LPS synthesis at wild-type levels, indicating that GutQ functions as an API inside the cell. The gut operon remained inducible in TCM7[(⌬gutQ)], suggesting that GutQ is not directly involved in D-glucitol catabolism. The conditional mutant TCM15[(⌬gutQ⌬kdsD)] was dependent on exogenous A5P both for LPS synthesis/growth and for upregulation of the gut operon. The phenotype was suppressed by complementation in trans with a plasmid encoding a functional copy of GutQ or by increasing the amount of A5P in the medium. As there is no obvious obligatory role for GutQ in the metabolism of D-glucitol and there is no readily apparent link between D-glucitol metabolism and LPS biosynthesis, it is suggested that A5P is not only a building block for KDO biosynthesis but also may be a regulatory molecule involved in expression of the gut operon.D-Arabinose 5-phosphate isomerase (API) is the first enzyme in the biosynthetic pathway of 3-deoxy-D-manno-octulosonate (KDO), a unique 8-carbon sugar component of lipopolysaccharides (LPSs). Lipopolysaccharides are amphiphilic macromolecules located in the outer leaflet of the outer membrane of gram-negative bacteria, forming an asymmetric lipid bilayer that surrounds the cell. The LPS layer is anchored in the outer membrane by the highly conserved lipid A domain and is followed by an oligosaccharide core region usually containing at least one KDO molecule that connects lipid A to an extended hypervariable repeating polysaccharide chain (O antigen) (25). In addition to providing a measure of intrinsic antibiotic resistance and defense against host responses, LPS (also referred to as endotoxin) is the main mediator of gramnegative bacterial pathogenesis (13, 33). The minimal LPS structure required for viability of Escherichia coli under laboratory conditions is KDO 2 -lipid A, also referred to as Re endotoxin (11,25,31).API catalyzes the reversible 1,2-keto/aldol isomerization of the pentose pathway intermediate ribulose 5-phosphate (Ru5P) to D-arabinose 5-phosphate (A5P) and is the intracellular source of A5P used f...

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“…Sorbitol was selected for this test because it is not effective at eliciting CCR (45), and it is transported by a sorbitol-specific PTS permease (10). Whereas all strains could grow with sorbitol as the sole carbohydrate, the lacA, lacB, and lacAB mutants were unable to grow on sorbitol when galactose or lactose was included in the medium.…”

Section: Resultsmentioning

confidence: 99%

“…Since there does not appear to be any direct role for ManL in the uptake of lactose, ManL may play additional roles beyond CCR (see below) in the regulation of uptake or catabolism of galactose and lactose, e.g., modulation of the activity of the lactose PTS or allosteric control of catabolic enzymes. Notably, the better growth on sorbitol of the strains lacking ManL may be partly attributable to enhanced expression of the genes for sorbitol utilization, since these genes have been shown to be more highly expressed in strain JAM1 (1,10). To gain a more comprehensive picture of the regulation of the lac operon by preferred carbohydrates, transcriptional activity of the lacA promoter was measured using the PlacA-cat reporter fusion in both UA159 and various EII mutants.…”

mentioning

confidence: 99%

Utilization of Lactose and Galactose by Streptococcus mutans : Transport, Toxicity, and Carbon Catabolite Repression

2010

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Abundant in milk and other dairy products, lactose is considered to have an important role in oral microbial ecology and can contribute to caries development in both adults and young children. To better understand the metabolism of lactose and galactose by Streptococcus mutans, the major etiological agent of human tooth decay, a genetic analysis of the tagatose-6-phosphate (lac) and Leloir (gal) pathways was performed in strain UA159. Deletion of each gene in the lac operon caused various alterations in expression of a P lacA -cat promoter fusion and defects in growth on either lactose (lacA, lacB, lacF, lacE, and lacG), galactose (lacA, lacB, lacD, and lacG) or both sugars (lacA, lacB, and lacG). Failure to grow in the presence of galactose or lactose by certain lac mutants appeared to arise from the accumulation of intermediates of galactose metabolism, particularly galatose-6-phosphate. The glucose-and lactose-PTS permeases, EII Man and EII Lac , respectively, were shown to be the only effective transporters of galactose in S. mutans. Furthermore, disruption of manL, encoding EIIAB Man , led to increased resistance to glucose-mediated CCR when lactose was used to induce the lac operon, but resulted in reduced lac gene expression in cells growing on galactose. Collectively, the results reveal a remarkably high degree of complexity in the regulation of lactose/galactose catabolism.Lactose, a ␤1,4-linked disaccharide of ␤-D-galactose and ␣/␤-D-glucose, is commonly found in the dairy-rich diets of most industrialized nations. Lactose is rapidly fermented by streptococci, including the cariogenic oral bacterium Streptococcus mutans (21), as well as by a variety of industrially important lactic acid bacteria (LAB) (19). Multiple pathways have been identified in bacteria for the utilization of lactose encountered in the environment. For example, Streptococcus salivarius strain 25975 (26) secretes a ␤-galactosidase that hydrolyzes extracellular lactose into galactose and glucose, although it is more common for lactose to be transported before cleavage (18). Most efficiently, and almost exclusively in Gram-positive bacteria, lactose is internalized by the phosphoenolpyruvate (PEP)-dependent sugar-phosphotransferase system (PTS), yielding lactose-6-phosphate (Lac-6-P) (36). The Lac-6-P is hydrolyzed to glucose and galactose-6-phosphate (Gal-6-P) by a cytoplasmic phospho-␤-galactosidase (LacG), and the Gal-6-P can be catabolized by the tagatose-6-phosphate pathway (18) (Fig. 1). Many bacteria, including Escherichia coli, Lactococcus lactis strain 7962, and S. salivarius strain 57.I, can internalize lactose through non-PTS transporters. Intracellular lactose is cleaved by a ␤-galactosidase enzyme and the D-galactose can directly enter the Leloir pathway ( Fig. 1) (18, 20).S. mutans has a functional lactose-specific PTS (14, 26) encoded by the lacF (EIIA) and lacE (EIIBC) genes (40). A phospho-␤-galactosidase (lacG) and the enzymes of the tagatose-6-phosphate pathway (Fig. 1B), including the two subunits of the heteromeri...

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Identification of the Operon for the Sorbitol (Glucitol) Phosphoenolpyruvate:Sugar Phosphotransferase System in Streptococcus mutans

Cited by 29 publications

References 34 publications

How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria

How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria

Identification of GutQ from Escherichia coli as a d -Arabinose 5-Phosphate Isomerase

Utilization of Lactose and Galactose by Streptococcus mutans : Transport, Toxicity, and Carbon Catabolite Repression

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