CelR-mediated activation of the cellobiose-utilization gene cluster in Streptococcus pneumoniae

Shafeeq, Sulman; Kloosterman, Tomas G.; Kuipers, Oscar P.

doi:10.1099/mic.0.051359-0

Cited by 31 publications

(51 citation statements)

References 34 publications

(66 reference statements)

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“…There is a growing body of literature identifying complex dietary carbohydrates as potential substrates for pneumococcal transporters (6,(34)(35)(36). It is challenging to determine whether these carbohydrates are the physiologically relevant substrates of these transporters.…”

Section: Discussionmentioning

confidence: 99%

The ABC Transporter Encoded at the Pneumococcal Fructooligosaccharide Utilization Locus Determines the Ability To Utilize Long- and Short-Chain Fructooligosaccharides

Linke¹,

Woodiga²,

Meyers³

et al. 2012

Journal of Bacteriology

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bStreptococcus pneumoniae is an important human pathogen that requires carbohydrates for growth. The significance of carbohydrate acquisition is highlighted by the genome encoding more than 27 predicted carbohydrate transporters. It has long been known that about 60% of pneumococci could utilize the fructooligosaccharide inulin as a carbohydrate source, but the mechanism of utilization was unknown. Here we demonstrate that a predicted sucrose utilization locus is actually a fructooligosaccharide utilization locus and imparts the ability of pneumococci to utilize inulin. Genes in strain TIGR4 predicted to encode an ABC transporter (SP_1796-8) and a ␤-fructosidase (SP_1795) are required for utilization of several fructooligosaccharides longer than kestose, which consists of two ␤(2-1)-linked fructose molecules with a terminal ␣(1-2)-linked glucose molecule. Similar to other characterized pneumococcal carbohydrate utilization transporter family 1 transporters, growth is dependent on the gene encoding the ATPase MsmK. While the majority of pneumococcal strains encode SP_1796-8 at this genomic location, 19% encode an alternative transporter. Although strains encoding either transporter can utilize short-chain fructooligosaccharides for growth, only strains encoding SP_1796-8 can utilize inulin. Exchange of genes encoding the SP_1796-8 transporter for those encoding the alternative transporter resulted in a TIGR4 strain that could utilize short-chain fructooligosaccharide but not inulin. These data demonstrate that the transporter encoded at this locus determines the ability of the bacteria to utilize long-chain fructooligosaccharides and explains the variation in inulin utilization between pneumococcal strains.

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Section: Discussionmentioning

confidence: 99%

The ABC Transporter Encoded at the Pneumococcal Fructooligosaccharide Utilization Locus Determines the Ability To Utilize Long- and Short-Chain Fructooligosaccharides

Linke¹,

Woodiga²,

Meyers³

et al. 2012

Journal of Bacteriology

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“…SPD_0247 encodes a putative protein annotated as a 6-phospho-␤-glucosidase (14). This putative protein (BglA3) has 459 amino acids and a predicted molecular mass of 53.2 kDa.…”

Section: Resultsmentioning

confidence: 99%

“…SPD_0247 is associated with neither a regulatory nor a transporter gene. This observation leads to the possibility that BglA3 is processing sugars transported by other loci, such as celBCD as well as SPD_0293 and SPD_0295-7 loci, which are implicated in cellobiose and hyaluronic acid transport, respectively (3,14,35). BglA3's involvement in the cleavage of sugars transported by multiple loci offers an explanation for the in vivo attenuation of ⌬SPD0247 despite the presence of multiple ␤-glucoside operons in S. pneumoniae.…”

Section: Discussionmentioning

confidence: 99%

“…This operon is responsible for the uptake of the ␤-glucosides cellobiose, gentiobiose, arbutin, amygdalin, and esculin (34). In addition, there are other loci implicated in ␤-glucoside utilization, such as SPD_0502-3 and SPD_1831-3 (4,14), which contain a gene coding for ␤-glucosidase. Previously, it was shown that the strains mutated in 6-phospho-␤-glucosidase genes, in SPD_0277, SPD_0502, or both, could grow as well as the wild-type strain on cellobiose, showing that it is possible to compensate for the lack of one or multiple 6-phospho-␤-glucosidases.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the celBCD region has been shown to be important for cellobiose metabolism (14). The activity of phospho-␤-glucosidases or phospho-␤-galactosidases is important for ␤-glucoside utilization, and the pneumococcus has six genes annotated as either 6-phosphogalactosidase or 6-phospho-␤-glucosidase (SPD_ 0247, SPD_277, SPD_0427, SPD_0503, SPD_1046, and SPD_ 1830) (15).…”

mentioning

confidence: 99%

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Pneumococcal 6-Phospho-β-Glucosidase (BglA3) Is Involved in Virulence and Nutrient Metabolism

et al. 2016

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For the generation of energy, the important human pathogen Streptococcus pneumoniae relies on host-derived sugars, including ␤-glucoside analogs. The catabolism of these nutrients involves the action of 6-phospho-␤-glucosidase to convert them into usable monosaccharaides. In this study, we characterized a 6-phospho-␤-glucosidase (BglA3) encoded by SPD_0247. We found that this enzyme has a cell membrane localization and is active only against a phosphorylated substrate. A mutated pneumococcal ⌬SPD0247 strain had reduced 6-phospho-glucosidase activity and was attenuated in growth on cellobiose and hyaluronic acid compared to the growth of wild-type D39. ⌬SPD0247-infected mice survived significantly longer than the wild-type-infected cohort, and the colony counts of the mutant were lower than those of the wild type in the lungs. The expression of SPD_0247 in S. pneumoniae harvested from infected tissues was significantly increased relative to its expression in vitro on glucose. Additionally, ⌬SPD0247 is severely impaired in its attachment to an abiotic surface. These results indicate the importance of ␤-glucoside metabolism in pneumococcal survival and virulence. Streptococcus pneumoniae is a frequent occupant of the human nasopharynx, where it resides without causing symptoms (1). Conversely, the bacterium also is a major human pathogen, being a leading cause of bacterial pneumonia, otitis media, meningitis, and septicemia (1). The increasing trend of antibiotic resistance and the shortcomings of existing vaccines mean that a better understanding of the pathogenesis of pneumococcal diseases is required.Almost one-third of the transporters in the pneumococcal genome are dedicated to sugars (2), stressing the important role that these carbon sources play in the ability of pneumococci to survive in the host. The pneumococcus has been shown to ferment 32 different sugars in vitro, including various hexoses, ␣-and ␤-galactosides, and glucosides, as well as polysaccharides (3, 4). However, the concentrations of readily available simple carbohydrates in the respiratory tract are low (5); thus, the pneumococcus relies on complex host glycans for growth in vivo (4). Central to this is the ability to sequentially deglycosylate host glycoproteins (6).Mammalian extracellular matrix is rich in glycosaminoglycans (GAGs; e.g., hyaluronic acid), which contain ␤-linked disaccharide repeating units (7,8). The degradation of GAGs leads to the generation of structural analogues of cellobiose or N,N=-diacetylchitobiose [(GlcNAc) 2 ] and other ␤-linked disaccharides (9). Disaccharides such as these can be transported into the bacterial cell through phosphoenolpyruvate-dependent phosphotransferase systems (PTS), which transport and phosphorylate sugars simultaneously (10). The phosphorylated disaccharides then are hydrolyzed by cytoplasmic phospho-␤-glucosidases (EC 3.2.1.86) or phospho-␤-galactosidases (EC 3.2.1.85) that usually do not have hydrolytic activity toward nonphosphorylated substrates. The resulting glucose and glucose 6-pho...

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Glycan‐metabolizing enzymes in microbe–host interactions: the Streptococcus pneumoniae paradigm

2018

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Streptococcus pneumoniae is a frequent colonizer of the upper airways; however, it is also an accomplished pathogen capable of causing life-threatening diseases. To colonize and cause invasive disease, this bacterium relies on a complex array of factors to mediate the host-bacterium interaction. The respiratory tract is rich in functionally important glycoconjugates that display a vast range of glycans, and, thus, a key component of the pneumococcus-host interaction involves an arsenal of bacterial carbohydrate-active enzymes to depolymerize these glycans and carbohydrate transporters to import the products. Through the destruction of host glycans, the glycan-specific metabolic machinery deployed by S. pneumoniae plays a variety of roles in the host-pathogen interaction. Here, we review the processing and metabolism of the major host-derived glycans, including N- and O-linked glycans, Lewis and blood group antigens, proteoglycans, and glycogen, as well as some dietary glycans. We discuss the role of these metabolic pathways in the S. pneumoniae-host interaction, speculate on the potential of key enzymes within these pathways as therapeutic targets, and relate S. pneumoniae as a model system to glycan processing in other microbial pathogens.

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CelR-mediated activation of the cellobiose-utilization gene cluster in Streptococcus pneumoniae

Cited by 31 publications

References 34 publications

The ABC Transporter Encoded at the Pneumococcal Fructooligosaccharide Utilization Locus Determines the Ability To Utilize Long- and Short-Chain Fructooligosaccharides

The ABC Transporter Encoded at the Pneumococcal Fructooligosaccharide Utilization Locus Determines the Ability To Utilize Long- and Short-Chain Fructooligosaccharides

Pneumococcal 6-Phospho-β-Glucosidase (BglA3) Is Involved in Virulence and Nutrient Metabolism

Glycan‐metabolizing enzymes in microbe–host interactions: the Streptococcus pneumoniae paradigm

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