Title: The Cell-Cell Communication Signal Indole Controls the Physiology and Interspecies Communication of Acinetobacter baumannii Cui B, Chen X, Guo Q, Song S, Wang M, Liu J, Deng Y Ref: Microbiol Spectr, :e0102722, 2022 : PubMed
Many bacteria utilize quorum sensing (QS) to control group behavior in a cell density-dependent manner. Previous studies have demonstrated that Acinetobacter baumannii employs an N-acyl-L-homoserine lactone (AHL)-based QS system to control biological functions and virulence. Here, we report that indole controls biological functions, virulence and AHL signal production in A. baumannii. The biosynthesis of indole is performed by A1S_3160 (AbiS, Acinetobacter baumannii indole synthase), which is a novel indole synthase annotated as an alpha/beta hydrolase in A. baumannii. Heterologous expression of AbiS in an Escherichia coli indole-deficient mutant also rescued the production of indole by using a distinct biosynthetic pathway from the tryptophanase TnaA, which produces indole directly from tryptophan in E. coli. Moreover, we revealed that indole from A. baumannii reduced the competitive fitness of Pseudomonas aeruginosa by inhibiting its QS systems and type III secretion system (T3SS). As A. baumannii and P. aeruginosa usually coexist in human lungs, our results suggest the crucial roles of indole in both the bacterial physiology and interspecies communication. IMPORTANCE Acinetobacter baumannii is an important human opportunistic pathogen that usually causes high morbidity and mortality. It employs the N-acyl-L-homoserine lactone (AHL)-type quorum sensing (QS) system, AbaI/AbaR, to regulate biological functions and virulence. In this study, we found that A. baumannii utilizes another QS signal, indole, to modulate biological functions and virulence. It was further revealed that indole positively controls the production of AHL signals by regulating abaI expression at the transcriptional levels. Furthermore, indole represses the QS systems and type III secretion system (T3SS) of P. aeruginosa and enhances the competitive ability of A. baumannii. Together, our work describes a QS signaling network where a pathogen uses to control the bacterial physiology and pathogenesis, and the competitive ability in microbial community.
Title: Predictive Value of Serum Lipoprotein-Associated Phospholipase A2 for Type 2 Diabetes Mellitus Complicated with Metabolic Syndrome in Elderly Patients Ren J, Chang M, Song S, Zhao R, Xing X, Chang X Ref: Clin Lab, 68:, 2022 : PubMed
BACKGROUND: The aim was to investigate the predictive value of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) for type 2 diabetes mellitus (T2DM) complicated with metabolic syndrome (MS) in elderly patients. METHODS: A total of 296 patients with T2DM admitted from January 2019 to January 2021 were enrolled and assigned to MS group (n = 181) and non-MS group (n = 115). Their clinical data and laboratory test results were compared. Logistic regression analysis was employed to identify independent risk factors for MS in T2DM patients. Spearman's analysis was utilized to explore the correlations between serum Lp-PLA2 level and detection indicators. The predictive value of Lp-PLA2 for MS was analyzed by plotting receiver operating characteristic (ROC) curve, and Cox regression model was applied to explore the correlation of serum Lp-PLA2 level with MS. The results of data subjected to multivariate analysis were used to construct prediction models. RESULTS: The incidence rate of MS was 61.15% in T2DM patients. MS group had a significantly higher serum level of Lp-PLA2 than non-MS group (p < 0.05). Serum Lp-PLA2 was significantly positively correlated to FBG, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), FINS, and HOMA-IR, but significantly negatively associated with LDL-C (p < 0.05). The area under the ROC curve of Lp-PLA2 for predicting MS in T2DM patients was 0.724 (95% CI: 0.625 - 0.826, p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of Lp-PLA2 with an optimal cutoff value of 82.96 ng/mL were 73.7%, 85.4%, 77.56%, and 93.24%, respectively. TC, TG, HDL-C, HbA1c, and Lp-PLA2 were independent risk factors for MS (p < 0.05). The area under the ROC curve of the risk prediction model established based on these indicators was 0.823, and the cutoff value, Youden index, sensitivity, and specificity were 0.219, 0.656, 78.87%, and 87.66%, respectively, indicating higher predictive value. CONCLUSIONS: Increased serum Lp-PLA2 level is an independent risk factor for MS in T2DM patients. Lp-PLA2 (82.87 ng/mL) has high predictive value for MS.
Among 276 herbal extracts, a methanol extract of Castanopsis cuspidata var. sieboldii stems was selected as an experimental source for novel acetylcholinesterase (AChE) inhibitors. Five compounds were isolated from the extract by activity-guided screening, and their inhibitory activities against butyrylcholinesterase (BChE), monoamine oxidases (MAOs), and beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) were also evaluated. Of these compounds, 4'-O-(alpha-L-rhamnopyranosyl)-3,3',4-tri-O-methylellagic acid (3) and 3,3',4-tri-O-methylellagic acid (4) effectively inhibited AChE with IC(50) values of 10.1 and 10.7 microM, respectively. Ellagic acid (5) inhibited AChE (IC(50) = 41.7 microM) less than 3 and 4. In addition, 3 effectively inhibited MAO-B (IC(50) = 7.27 microM) followed by 5 (IC(50) = 9.21 microM). All five compounds weakly inhibited BChE and BACE-1. Compounds 3, 4, and 5 reversibly and competitively inhibited AChE, and were slightly or non-toxic to MDCK cells. The binding energies of 3 and 4 (- 8.5 and - 9.2 kcal/mol, respectively) for AChE were greater than that of 5 (- 8.3 kcal/mol), and 3 and 4 formed a hydrogen bond with Tyr124 in AChE. These results suggest 3 is a dual-targeting inhibitor of AChE and MAO-B, and that these compounds should be viewed as potential therapeutics for the treatment of Alzheimer's disease.
Various boron-containing drugs have been approved for clinical use over the past two decades, and more are currently in clinical trials. The increasing interest in boron-containing compounds is due to their unique binding properties to biological targets; for example, boron substitution can be used to modulate biological activity, pharmacokinetic properties, and drug resistance. In this perspective, we aim to comprehensively review the current status of boron compounds in drug discovery, focusing especially on progress from 2015 to December 2020. We classify these compounds into groups showing anticancer, antibacterial, antiviral, antiparasitic and other activities, and discuss the biological targets associated with each activity, as well as potential future developments.
Title: Dietary administration of probiotic Lactobacillus rhamnosus modulates the neurological toxicities of perfluorobutanesulfonate in zebrafish Liu M, Song S, Hu C, Tang L, Lam JCW, Lam PKS, Chen L Ref: Environ Pollut, 265:114832, 2020 : PubMed
Perfluorobutanesulfonate (PFBS), an aquatic pollutant of emerging concern, is found to disturb the neural signaling along gut-brain axis, whereas probiotic additives have been applied to improve neuroendocrine function of teleosts. Both PFBS and probiotics can commonly target nervous system. However, whether and how probiotic bacteria can modulate the neurotoxicities of PFBS remain not explored. It is thus necessary to elucidate the probiotic modulation of PFBS neurotoxicity, which can provide implications to the application of probiotic bacteria in aquaculture industry. In the present study, adult zebrafish were exposed to 0, 10 and 100 mug/L PFBS with or without dietary administration of probiotic Lactobacillus rhamnosus. Interaction between PFBS and probiotic along gut-brain axis was examined, covering three dominant pathways (i.e., neurotransmission, immune response and hypothalamic-pituitary-adrenal (HPA) axis). The results showed that, compared to the single effects, PFBS and probiotic coexposure significantly altered the acetylcholinesterase activity and neurotransmitter profiles in gut and brain of zebrafish, with mild effects on neuronal integrity. Neurotransmitters closely correlated reciprocally in intestines, which, however, was distinct from the correlation profile in brains. In addition, PFBS and probiotic were combined to impact brain health through absorption of bacterial lipopolysaccharides and production of inflammatory cytokines. Relative to neurotransmission and immune signaling, HPA axis was not involved in the neurotoxicological interaction between PFBS and probiotic. Furthermore, it needs to point out that interactive modes between PFBS and probiotic varied a lot, depending on exposure concentrations, sex and toxic indices. Overall, the present study provided the first evidence that probiotic supplement could dynamically modulate the neurotoxicities of PFBS in teleost.
Fucosylated chondroitin sulfate from sea cucumber Stichopus japonicus (FCSSJ) has been demonstrated with various biological activities; however, its precise structure is still controversial, and digestive behavior remains poorly understood. FCSSJ was purified, and its detailed structure was elucidated mainly based on the NMR spectroscopic methods. Its main chain was characterized as -->4)-beta-d-GlcA-(1 --> 3)-beta-d-GalNAc-(1--> with GalNAc4S6S:GalNAc4S in a ratio of 1.5:1, and three types of sulfated fucosyl branches attaching C-3 of GlcA, namely, Fucp2S4S, Fucp3S4S, and Fucp4S, were found in a ratio of 2:1.5:1. The digestibility of FCSSJ was investigated in vitro, and the unchanged molecular weight and reducing sugar content indicated that FCSSJ was not broken down under salivary and gastrointestinal digestion. Furthermore, FCSSJ showed a significant inhibitory impact on pancreatic lipase dose-dependently but not on alpha-amylase, indicating that the inhibition of pancreatic lipase by FCSSJ might be a pathway for its hypolipidemic effect. These findings propose a fucosylated chondroitin sulfate and provide insight into the mechanism of its physiological effects in the digestion system.
Di(2-ethylhexyl) phthalate (DEHP), a plasticizer of synthetic polymers, is a well-known endocrine disrupting chemical (EDC) and reproductive toxicant. Addressing the unclear mechanism of DEHP-induced reproductive dysfunction, this study used GC-2spd cells to investigate the molecular mechanism involved in the DEHP-induced toxicity in the male reproductive system. The results indicated that the apoptotic cell death was significantly induced by DEHP exposure over 100 muM. Furthermore, DEHP treatment could induce oxidative stress in GC-2spd cells involving in the decrease of superoxide dismutase (SOD) activity (200 muM) and glutathione peroxidase (GSH-Px) activity (50 and 100 muM). In addition, DEHP induction also caused the elevated ratios of Bax/Bcl-2, release of cytochrome c and decomposition of procaspase-3 and procaspase-9 in GC-2spd cells. Taken together, our work provided the evidence that DEHP exposure might induce apoptosis of GC-2spd cells via mitochondria pathway mediated by oxidative stress.
Title: ace-3 plays an important role in phoxim resistance in Caenorhabditis elegans Han Y, Song S, Guo Y, Zhang J, Ma E Ref: Ecotoxicology, 25:835, 2016 : PubMed
Organophosphorus and carbamate are widely used in agricultural production. Caenorhabditis elegans is a model organism that is widely used in various toxicology studies. To understand the effects of two types of commonly used pesticides, phoxim (organophosphorus) and carbaryl (carbamate), we determined the activities of acetylcholinesterases (AChEs) and detected the expression of four ace genes by RT-qPCR in C. elegans following treatment with these pesticides. The results showed that phoxim and carbaryl could reduce acetylcholinesterase activities and up-regulate the ace-3 mRNA expression levels. We also detected the toxic effects of these pesticides on the ace-3 deletion mutant dc-2, and found that some characteristics, including LC50, development, movement, reproduction and lifespan, were reduced in the dc-2 mutant. However, the toxic effects of carbaryl were weaker than those of phoxim. Carbaryl treatment did not significantly affect the LC50, movement ability or lifespan. Interestingly, body and brood size increased with carbaryl treatment at low concentrations. These data showed that both phoxim and carbaryl could inhibit AChE but that the ace-3 was necessary for phoxim detoxification. The LC50 of phoxim and carbaryl in wild type N2 and the ace-3 deletion mutant dc-2. **Higher significant differences (P < 0.01).
Title: Characterization of a thermostable beta-glucosidase from Aspergillus fumigatus Z5, and its functional expression in Pichia pastoris X33 Liu D, Zhang R, Yang X, Zhang Z, Song S, Miao Y, Shen Q Ref: Microb Cell Fact, 11:25, 2012 : PubMed
BACKGROUND: Recently, the increased demand of energy has strongly stimulated the research on the conversion of lignocellulosic biomass into reducing sugars for the subsequent production, and beta-glucosidases have been the focus because of their important roles in a variety fundamental biological processes and the synthesis of useful beta-glucosides. Although the beta-glucosidases of different sources have been investigated, the amount of beta-glucosidases are insufficient for effective conversion of cellulose. The goal of this work was to search for new resources of beta-glucosidases, which was thermostable and with high catalytic efficiency. RESULTS: In this study, a thermostable native beta-glucosidase (nBgl3), which is secreted by the lignocellulose-decomposing fungus Aspergillus fumigatus Z5, was purified to electrophoretic homogeneity. Internal sequences of nBgl3 were obtained by LC-MS/MS, and its encoding gene, bgl3, was cloned based on the peptide sequences obtained from the LC-MS/MS results. bgl3 contains an open reading frame (ORF) of 2622 bp and encodes a protein with a predicted molecular weight of 91.47 kDa; amino acid sequence analysis of the deduced protein indicated that nBgl3 is a member of the glycoside hydrolase family 3. A recombinant beta-glucosidase (rBgl3) was obtained by the functional expression of bgl3 in Pichia pastoris X33. Several biochemical properties of purified nBgl3 and rBgl3 were determined - both enzymes showed optimal activity at pH 6.0 and 60 degrees C, and they were stable for a pH range of 4-7 and a temperature range of 50 to 70 degrees C. Of the substrates tested, nBgl3 and rBgl3 displayed the highest activity toward 4-Nitrophenyl-beta-D-glucopyranoside (pNPG), with specific activities of 103.5 +/- 7.1 and 101.7 +/- 5.2 U mg-1, respectively. However, these enzymes were inactive toward carboxymethyl cellulose, lactose and xylan. CONCLUSIONS: An native beta-glucosidase nBgl3 was purified to electrophoretic homogeneity from the crude extract of A. fumigatus Z5. The gene bgl3 was cloned based on the internal sequences of nBgl3 obtained from the LC-MS/MS results, and the gene bgl3 was expressed in Pichia pastoris X33. The results of various biochemical properties of two enzymes including specific activity, pH stability, thermostability, and kinetic properties (Km and Vmax) indicated that they had no significant differences.
Bifidobacterium longum subsp. longum BBMN68 was isolated from the feces of a healthy centenarian living in an area of BaMa, Guangxi, China, known for longevity. Here we report the main genome features of B. longum strain BBMN68 and the identification of several predicted proteins associated with the ecological niche of longevity.
Title: N-butyryl-homoserine lactone, a bacterial quorum-sensing signaling molecule, induces intracellular calcium elevation in Arabidopsis root cells Song S, Jia Z, Xu J, Zhang Z, Bian Z Ref: Biochemical & Biophysical Research Communications, 414:355, 2011 : PubMed
N-acyl-L-homoserine lactones (AHLs) are quorum sensing (QS) signal molecules that are commonly used in gram-negative bacteria. Recently, it has become evident that AHLs can influence the behavior of plant cells. However, little is known about the mechanism of the plants' response to these bacterial signals. Calcium ions (Ca(2+)), ubiquitous intracellular second messengers, play an essential role in numerous signal transduction pathways in plants. In this study, the cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) was measured by a luminometric method in the excised root cells of Arabidopsis plants that were treated with N-butyryl-homoserine lactone (C4-HSL). There was a transient and immediate increase in [Ca(2+)](cyt) levels, and the highest level (0.4 muM), approximately 2-fold higher than the basal level, was observed at the 6th second after the addition of 10 muM C4-HSL. Pretreatments with La(3+), verapamil or ethylene glycol tetraacetic acid (EGTA) inhibited the increase in [Ca(2+)](cyt) caused by C4-HSL, whereas it remained unaffected by pretreatment with Li(+), indicating that the Ca(2+) contributing to the increase in [Ca(2+)](cyt) was mobilized from the extracellular medium via the plasma membrane Ca(2+) channels but not from the intracellular Ca(2+) stores. Furthermore, electrophysiological approaches showed that the transmembrane Ca(2+) current was significantly increased with the addition of C4-HSL. Taken together, our observations suggest that C4-HSL may act as an elicitor from bacteria to plants and that Ca(2+) signaling participates in the ability of plant cells to sense the bacterial QS signals.
Title: Disposable screen-printed electrode coupled with recombinant Drosophila melanogaster acetylcholinesterase and multiwalled carbon nanotubes for rapid detection of pesticides Tang Z, Chen H, Song S, Fan C, Zhang D, Wu A Ref: Journal of AOAC International, 94:307, 2011 : PubMed
Recombinant Drosophila melanogaster acetylcholinesterase (R-DmAChE), multiwalled carbon nanotubes (MWCNTs), and Prussian blue have been combined for development of a three-electrode biosensor with more rapid responses and higher stability than in our previous study. A new disposable screen-printed electrode (SPE) was developed for rapid detection of organophosphate and carbamate pesticides. After optimization, 10 microg MWCNT and 5 microL enzyme immobilization solution consisting of 0.2% glutaraldehyde, 0.1% Nafion, 0.2% bovine serum albumin, 0.1 g/L MWCNT, and 1.5 mU R-DmAChE were fixed on each of the R-DmAChE/MWCNT SPEs. The LOD of this biosensor was 0.5 microg/L for pesticide standards of dichlorvos (DDV) and carbofuran. The performance of this biosensor was tested for vegetable and water samples at various spiked levels, and good stability and sensitivity were found. The obtained recoveries were from 82.6 to 110.5% for DDV at levels of 0.5-5 microg/L and 73.4 to 118.4% for carbofuran at 1-10 microg/L in lake and sea water samples, demonstrating that the proposed approach is an alternative means for rapid detection of pesticide residues and contaminants in food safety and environmental monitoring.
Title: Complete genome sequence of the pathogenic bacterium Riemerella anatipestifer strain RA-GD Yuan J, Liu W, Sun M, Song S, Cai J, Hu S Ref: Journal of Bacteriology, 193:2896, 2011 : PubMed
Riemerella anatipestifer is a well-described pathogen of waterfowl and other avian species which can cause a great loss to the poultry industry. Here we obtained the complete genome sequence of R. anatipestifer strain RA-GD, which was isolated from an infected duck in Guangzhou, China, and was cultivated in our laboratory.
Title: Regulation of cholinergic neurotransmitter phenotypes. Salvaterra PM, Lee M, Song S Ref: Cholinergic Mechanisms, CRC Press, :193, 2004 : PubMed
