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Inhibition of interaction between Staphylococcus aureus ?-hemolysin and erythrocytes membrane by hydrolysable tannins: structure-related activity study.

ABSTRACT: The objective of the study was a comparative analysis of the antihemolytic activity against two Staphylococcus aureus strains (8325-4 and NCTC 5655) as well as ?-hemolysin and of the membrane modifying action of four hydrolysable tannins with different molecular mass and flexibility: 3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-?-D-glucose (T1), 1,2,3,4,5-penta-O-galloyl-?-D-glucose (T2), 3-O-galloyl-1,2-valoneoyl-?-D-glucose (T3) and 1,2-di-O-galloyl-4,6-valoneoyl-?-D-glucose (T4). We showed that all the compounds studied manifested antihemolytic effects in the range of 5-50 µM concentrations. However, the degree of the reduction of hemolysis by the investigated tannins was not uniform. A valoneoyl group-containing compounds (T3 and T4) were less active. Inhibition of the hemolysis induced by ?-hemolysin was also noticed on preincubated with the tannins and subsequently washed erythrocytes. In this case the efficiency again depended on the tannin structure and could be represented by the following order: T1?>?T2?>?T4?>?T3. We also found a relationship between the degree of antihemolytic activity of the tannins studied and their capacity to increase the ordering parameter of the erythrocyte membrane outer layer and to change zeta potential. Overall, our study showed a potential of the T1 and T2 tannins as anti-virulence agents. The results of this study using tannins with different combinations of molecular mass and flexibility shed additional light on the role of tannin structure in activity manifestation.

SUBMITTER: Olchowik-Grabarek E

PROVIDER: S-EPMC7341856 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Inhibition of interaction between Staphylococcus aureus α-hemolysin and erythrocytes membrane by hydrolysable tannins: structure-related activity study.

Olchowik-Grabarek Ewa E Sekowski Szymon S Bitiucki Maciej M Dobrzynska Izabela I Shlyonsky Vadim V Ionov Maksim M Burzynski Paweł P Roszkowska Anna A Swiecicka Izabela I Abdulladjanova Nodira N Zamaraeva Maria M

Scientific reports 20200707 1

The objective of the study was a comparative analysis of the antihemolytic activity against two Staphylococcus aureus strains (8325-4 and NCTC 5655) as well as α-hemolysin and of the membrane modifying action of four hydrolysable tannins with different molecular mass and flexibility: 3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-β-D-glucose (T1), 1,2,3,4,5-penta-O-galloyl-β-D-glucose (T2), 3-O-galloyl-1,2-valoneoyl-β-D-glucose (T3) and 1,2-di-O-galloyl-4,6-valoneoyl-β-D-glucose (T4). We showed that ...[more]

PMID: 32636484

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Project description:We investigated the effect of andrographolide (AP) on the hemolytic capacity of Staphylococcus aureus (S. aureus) isolated from our region. AP is a labdane diterpenoid isolated from the stem and leaves of Andrographis paniculata. The hla gene from 234 S. aureus strains and the quality control standard strain ATCC29213 in dairy cows in some areas of Ningxia was analyzed. Evolutionary analysis, homology modeling, and functional enrichment annotation of α-hemolysin Hla detected from our region were performed through bioinformatics. The hemolytic ability of S. aureus isolates from the region was examined using the hemolysis test, and the effect of AP on S. aureus was quantified. Moreover, the effect of AP on the transcript levels of hla and genes highly related to hla (i.e., clfA and fnbA) was examined through fluorescence quantitative PCR. The mode of action of AP on the detected Hla was analyzed through molecular docking and dynamic simulation. The results showed that S. aureus in our region has a high rate of hla carriage. The hemolytic activity of strains NM98 and XF10 was significant, and ATCC29213 also exhibited some hemolytic activity. AP could inhibit the expression of Hla and its related proteins by downregulating hla, clfA, and fnbA transcript levels, which in turn attenuated the S. aureus hemolytic activity. Meanwhile, the AP molecule can form three hydrogen bonds with residues ASN105, SER106, and THR155 of Hla protein; bind with PRO103 through alkyl intermolecular forces; and form carbon hydrogen bonds with LYS154, reflecting that the AP molecule has a comparatively ideal theoretical binding activity with Hla protein. Among them, PRO103 and LYS154 are highly conserved in Hla protein molecules and play pivotal roles in the biological functions of Hla, and their binding may affect these functions. Their binding may also prevent the conformational transition of Hla from a monomer to an oligomer, thus inhibiting Hla hemolytic activity. This study offers a molecular basis for use of AP as an antivirulence drug and new ideas for developing novel drugs against S. aureus infection.

Dataset Information

Inhibition of interaction between Staphylococcus aureus ?-hemolysin and erythrocytes membrane by hydrolysable tannins: structure-related activity study.

Publications

Inhibition of interaction between Staphylococcus aureus α-hemolysin and erythrocytes membrane by hydrolysable tannins: structure-related activity study.

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