N-acetylglucosamine-Mediated Expression of nagA and nagB in Streptococcus pneumoniae

Afzal, Muhammad; Shafeeq, Sulman; Manzoor, Irfan; Henriques‐Normark, Birgitta; Kuipers, Oscar P.

doi:10.3389/fcimb.2016.00158

Cited by 8 publications

(10 citation statements)

References 71 publications

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“…Previous studies examining the role of EA usage on the growth of E. faecalis utilized a modified M9 minimal medium buffered with HEPES and supplemented with yeast extract (7). To ensure control over the content of our medium, particularly the source(s) of carbon, a strictly defined chemical medium (CDM) was designed and purchased (see Table S1 in the supplemental material) based on defined medium that was used previously for growth studies of other Gram-positive cocci (21)(22)(23)(24). Because ethanolamine utilization requires the presence of the cofactor AdoCbl (7, 10), 40 g/ml AdoCbl was added to the base CDM.…”

Section: Resultsmentioning

confidence: 99%

Ethanolamine Utilization and Bacterial Microcompartment Formation Are Subject to Carbon Catabolite Repression

et al. 2019

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Ethanolamine (EA) is a compound prevalent in the gastrointestinal (GI) tract that can be used as a carbon, nitrogen, and/or energy source. Enterococcus faecalis, a GI commensal and opportunistic pathogen, contains approximately 20 ethanolamine utilization (eut) genes encoding the necessary regulatory, enzymatic, and structural proteins for this process. Here, using a chemically defined medium, two regulatory factors that affect EA utilization were examined. First, the functional consequences of loss of the small RNA (sRNA) EutX on the efficacy of EA utilization were investigated. One effect observed, as loss of this negative regulator causes an increase in eut gene expression, was a concomitant increase in the number of catabolic bacterial microcompartments (BMCs) formed. However, despite this increase, the growth of the strain was repressed, suggesting that the overall efficacy of EA utilization was negatively affected. Second, utilizing a deletion mutant and a complement, carbon catabolite control protein A (CcpA) was shown to be responsible for the repression of EA utilization in the presence of glucose. A predicted cre site in one of the three EA-inducible promoters, PeutS, was identified as the target of CcpA. However, CcpA was shown to affect the activation of all the promoters indirectly through the two-component system EutV and EutW, whose genes are under the control of the PeutS promoter. Moreover, a bioinformatics analysis of bacteria predicted to contain CcpA and cre sites revealed that a preponderance of BMCcontaining operons are likely regulated by carbon catabolite repression (CCR). IMPORTANCE Ethanolamine (EA) is a compound commonly found in the gastrointestinal (GI) tract that can affect the behavior of human pathogens that can sense and utilize it, such as Enterococcus faecalis and Salmonella. Therefore, it is important to understand how the genes that govern EA utilization are regulated. In this work, we investigated two regulatory factors that control this process. One factor, a small RNA (sRNA), is shown to be important for generating the right levels of gene expression for maximum efficiency. The second factor, a transcriptional repressor, is important for preventing expression when other preferred sources of energy are available. Furthermore, a global bioinformatics analysis revealed that this second mechanism of transcriptional regulation likely operates on similar genes in related bacteria.

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Section: Resultsmentioning

confidence: 99%

Ethanolamine Utilization and Bacterial Microcompartment Formation Are Subject to Carbon Catabolite Repression

et al. 2019

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“…A study of truncated forms of StrH [52], and detailed biochemical and structural analysis of GH20A and GH20B in isolation [54,55], has revealed complementary specificities for the two GH20 domains. Import of the GlcNAc residues released by StrH is thought to occur via a promiscuous PTS transporter such as SP_0282-5 or ManLMN [23, 56,57]. 3) and a-(1?6) arms of complex N-glycans, whereas mutants of GH20B only recognize the a-(1?3) arm; however, unlike GH20A, GH20B is able to bind GlcNAc-bisected glycans.…”

Section: Degradation and Transport Of N-linked Glycansmentioning

confidence: 99%

“…Overall, it appears that the two GH20 domains of StrH may have co-evolved to allow efficient cleavage of all variations of complex N-glycans. Import of the GlcNAc residues released by StrH is thought to occur via a promiscuous PTS transporter such as SP_0282-5 or ManLMN [23, 56,57].…”

Section: Degradation and Transport Of N-linked Glycansmentioning

confidence: 99%

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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“…A key distinction between the fucosylated glycan degradation pathways described here and those encoded by the type 1/2 operons is the cellular location in which defucosylation occurs. S. pneumoniae is able to import galactose and GlcNAc, which would be released from histo-blood group antigens extracellularly by BgaA and BgaC, and use them as a carbon source for growth (12,59,60); however, it is unable to grow on exogenous fucose (54,56). Both type 1 and 2 fucose utilization operons are known or predicted to import fucosylated glycans and utilize intracellular ␣-fucosidases.…”

Section: Fucosylated Glycan Degradation By S Pneumoniaementioning

confidence: 99%

Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens

Hobbs

Pluvinage

Robb

et al. 2019

Journal of Biological Chemistry

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An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans. The pneumococcus can degrade a variety of complex glycans, including Nand O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae. Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histoblood group antigens, is largely unknown. Here, we identified two pneumococcal enzymes, SpGH29 C and SpGH95 C , that target ␣-(133/4) and ␣-(132) fucosidic linkages, respectively. X-ray crystallography studies combined with functional assays revealed that SpGH29 C is specific for the Lewis A and Lewis X antigen motifs and that SpGH95 C is specific for the H(O)-antigen motif. Together, these enzymes could defucosylate Lewis Y and Lewis B antigens in a complementary fashion. In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes. These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of ␣-fucosidases in this. Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the ␣-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction. This work was supported by Canadian Institutes of Health Research Operating Grant PJT 159786. The authors declare that they have no conflicts of interest with the contents of this article. This article contains Figs. S1-S4 and Table S1. The atomic coordinates and structure factors (codes 6ORG, 6ORF, 6ORH, and 6OR4) have been deposited in the Protein Data Bank (http://wwpdb.org/).

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N-acetylglucosamine-Mediated Expression of nagA and nagB in Streptococcus pneumoniae

Cited by 8 publications

References 71 publications

Ethanolamine Utilization and Bacterial Microcompartment Formation Are Subject to Carbon Catabolite Repression

Ethanolamine Utilization and Bacterial Microcompartment Formation Are Subject to Carbon Catabolite Repression

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

Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens

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