Dataset Information

Inhibition of Pneumolysin Cytotoxicity by Hydrolysable Tannins.

ABSTRACT: Streptococcus pneumoniae causes invasive infections such as otitis media, pneumonia and meningitis. It produces the pneumolysin (Ply) toxin, which forms a pore onto the host cell membrane and has multiple functions in the pathogenesis of S. pneumoniae. The Ply C-terminal domain 4 mediates binding to membrane cholesterol and induces the formation of pores composed of up to 40 Ply monomers. Ply has a key role in the establishment of nasal colonization, pneumococcal transmission from host to host and pathogenicity. Altogether, 27 hydrolysable tannins were tested for Ply inhibition in a hemolysis assay and a tannin-protein precipitation assay. Pentagalloylglucose (PGG) and gemin A showed nanomolar inhibitory activity. Ply oligomerization on the erythrocyte surface was inhibited with PGG. PGG also inhibited Ply cytotoxicity to A549 human lung epithelial cells. Molecular modelling of Ply interaction with PGG suggests that it binds to the pocket formed by domains 2, 3 and 4. In this study, we reveal the structural features of hydrolysable tannins that are required for interaction with Ply. Monomeric hydrolysable tannins containing three to four flexible galloyl groups have the highest inhibitory power to Ply cytotoxicity and are followed by oligomers. Of the oligomers, macrocyclic and C-glycosidic structures were weaker in their inhibition than the glucopyranose-based oligomers. Accordingly, PGG-type monomers and oligomers might have therapeutic value in the targeting of S. pneumoniae infections.

SUBMITTER: Maatsola S

PROVIDER: S-EPMC7766327 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Inhibition of Pneumolysin Cytotoxicity by Hydrolysable Tannins.

Maatsola Santeri S Kurkinen Sami S Engström Marica T MT Nyholm Thomas K M TKM Pentikäinen Olli O Salminen Juha-Pekka JP Haataja Sauli S

Antibiotics (Basel, Switzerland) 20201221 12

<i>Streptococcus pneumoniae</i> causes invasive infections such as otitis media, pneumonia and meningitis. It produces the pneumolysin (Ply) toxin, which forms a pore onto the host cell membrane and has multiple functions in the pathogenesis of <i>S. pneumoniae</i>. The Ply C-terminal domain 4 mediates binding to membrane cholesterol and induces the formation of pores composed of up to 40 Ply monomers. Ply has a key role in the establishment of nasal colonization, pneumococcal transmission from ...[more]

PMID: 33371182

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Project description:Terminalia ferdinandiana Exell., also known as Kakadu plum, is a wild-harvested native Australian fruit with limited information on how maturity is affecting the phytonutritional properties and bioactivities of the fruit. Thus, this study investigated changes in hydrolysable tannins, phenolic acids, sugar profile, standard physicochemical parameters, and antioxidant-scavenging capacity of wild-harvested Kakadu plum fruits at four different maturity stages, from immature to fully mature. Fruits harvested <25, 25-50, 50-75, and 75-100% degree of fullness were classified as highly immature (stage 1), immature (stage 2), semi-mature (stage 3), and fully mature (stage 4), respectively. Results showed that chebulagic acid, geraniin, chebulinic acid, castalagin, punicalagin, and gallic acid continuously decreased during fruit maturity, while elaeocarpusin, helioscopin B, corilagin, 3,4,6-tri-O-galloyl-S-glucose, and ellagic acid increased at the beginning of fruit growth (from stage 1 to 2), but decreased when the fruits reached their full maturity (stage 4). The levels of hydrolysable tannins and phenolic acids in fully mature fruits (stage 4) were significantly (p ≤ 0.05) lower than that in their immature counterparts (stages 1 and 2). Total phenolic content (TPC) and DPPH antioxidant radical-scavenging activity did not vary significantly between different maturity stages. Pearson's correlation coefficient test indicated that TPC and DPPH positively (p ≤ 0.05) correlate with most of the studied tannin compounds. Sugars (glucose, fructose, and sucrose), total soluble solid content, and titratable acidity increased during the fruit development. Furthermore, principal component analysis (PCA) revealed the difference between the immature and mature samples, based on their nutritional profile and bioactive compounds. The PCA results also suggested a considerable variability between the individual trees, highlighting the challenges of wild-harvest practice.

Project description:BACKGROUND:The outer peels of pomegranate (Punica granatum L.) possess two groups of polyphenols that have health beneficial properties: anthocyanins (ATs, which also affect peel color); and hydrolysable tannins (HTs). Their biosynthesis intersects at 3-dehydroshikimate (3-DHS) in the shikimate pathway by the activity of shikimate dehydrogenase (SDH), which converts 3-DHS to shikimate (providing the precursor for AT biosynthesis) or to gallic acid (the precursor for HTs biosynthesis) using NADPH or NADP+ as a cofactor. The aim of this study is to gain more knowledge about the factors that regulate the levels of HTs and ATs, and the role of SDH. RESULTS:The results have shown that the levels of ATs and HTs are negatively correlated in the outer fruit peels of 33 pomegranate accessions, in the outer peels of two fruits exposed to sunlight, and in those covered by paper bags. When calli obtained from the outer fruit peel were subjected to light/dark treatment and osmotic stresses (imposed by different sucrose concentrations), it was shown that light with high sucrose promotes the synthesis of ATs, while dark at the same sucrose concentration promotes the synthesis of HTs. To verify the role of SDH, six PgSDHs (PgSDH1, PgSDH3-1,2, PgSDH3a-1,2 and PgSDH4) were identified in pomegranate. The expression of PgSDH1, which presumably contributes to shikimate biosynthesis, was relatively constant at different sucrose concentrations. However, the transcript levels of PgSDH3s and PgSDH4 increased with the accumulation of gallic acid and HTs under osmotic stress, which apparently accumulates to protect the cells from the stress. CONCLUSIONS:The results strongly suggest that the biosynthesis of HTs and ATs competes for the same substrate, 3-DHS, and that SDH activity is regulated not only by the NADPH/NADP+ ratio, but also by the expression of the PgSDHs. Since the outer peel affects the customer's decision regarding fruit consumption, such knowledge could be utilized for the development of new genetic markers for breeding pomegranates having higher levels of both ATs and HTs.

Dataset Information

Inhibition of Pneumolysin Cytotoxicity by Hydrolysable Tannins.

Publications

Inhibition of Pneumolysin Cytotoxicity by Hydrolysable Tannins.

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