Dataset Information

Chemoenzymatic synthesis of sialylated lactuloses and their inhibitory effects on Staphylococcus aureus.

ABSTRACT:

Background

Sialylated glycoconjugates play important roles in physiological and pathological processes. However, available sialylated oligosaccharides source is limited which is a barrier to study their biological roles. This work reports an efficient approach to produce sialic acid-modified lactuloses and investigates their inhibitory effects on Staphylococcus aureus (S. aureus).

Methods

A one-pot two-enzyme (OPTE) sialylation system was used to efficiently synthesize sialylated lactuloses. Silica gel flash chromatography column was employed to purify the sialylated products. The purity and identity of the product structures were confirmed with mass spectrometry (MS) and nuclear magnetic resonance (NMR). The inhibitory effect of sialylated lactuloses against S. aureus was evaluated by using microplate assay, fluorescence microscopy, DAPI (4',6-diamidino-2-phenylindole) fluorescence staining and protein leakage quantification.

Results

Neu5Ac-containing sialylated lactuloses with either ?2,3- or ?2,6-linkages were efficiently synthesized via an efficient OPTE sialylation system using ?-2,3-sialyltransferase or ?-2,6-sialyltransferase, respectively. Neu5Ac-?2,3-lactulose and Neu5Ac-?2,6-lactulose significantly inhibited the growth of S. aureus. Fluorescence microscopy and DAPI fluorescence staining indicated that the sialylated lactuloses might disrupt nucleic acid synthesis of S. aureus.

Conclusions

Neu5Ac-containing sialylated lactuloses had higher antibacterial activity against S. aureus than non-sialylated lactulose. The inhibitory effect of Neu5Ac-?2,3-lactulose was superior to that of Neu5Ac-?2,6-lactulose. The sialylated lactuloses might inhibit S. aureus by causing cell membrane leakage and disrupting nucleic acid synthesis.

SUBMITTER: Zeng J

PROVIDER: S-EPMC6010273 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Chemoenzymatic synthesis of sialylated lactuloses and their inhibitory effects on Staphylococcus aureus.

Zeng Jie J Hu Yajie Y Jia Tian T Zhang Ruiyao R Su Tongchao T Sun Junliang J Gao Haiyan H Li Guanglei G Cao Meng M Song Mengdi M

PloS one 20180620 6

<h4>Background</h4>Sialylated glycoconjugates play important roles in physiological and pathological processes. However, available sialylated oligosaccharides source is limited which is a barrier to study their biological roles. This work reports an efficient approach to produce sialic acid-modified lactuloses and investigates their inhibitory effects on Staphylococcus aureus (S. aureus).<h4>Methods</h4>A one-pot two-enzyme (OPTE) sialylation system was used to efficiently synthesize sialylated ...[more]

PMID: 29924858

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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

Chemoenzymatic synthesis of sialylated lactuloses and their inhibitory effects on Staphylococcus aureus.

Background

Methods

Results

Conclusions

Publications

Chemoenzymatic synthesis of sialylated lactuloses and their inhibitory effects on Staphylococcus aureus.

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