Dencichine attenuates the virulence of Fusobacterium nucleatum by targeting hydrogen sulfide-producing enzyme.

Oral opportunistic pathogen Fusobacterium nucleatum can participate in various disease processes through the metabolite hydrogen sulfide, such as halitosis and colorectal cancer. The object of this study is to identify inhibitor capable of suppressing Fn1220, which is the principal hydrogen sulfide-producing enzyme in F. nucleatum. Through this inhibition, we aim to reduce the hydrogen sulfide production of F. nucleatum, consequently diminishing its virulence. Employing molecular docking techniques for inhibitor screening, we identified dencichine as the monomeric compound from Chinese medicine exhibiting the lowest binding energy to Fn1220 among a set of 27,045 candidates, and evaluated in vitro the ability of dencichine to inhibit hydrogen sulfide production using bismuth chloride method. Additionally, we investigated its impact on key virulence factors, including biofilm formation, hemolysis, and adhesion factors of F. nucleatum, using the crystalline violet method, sheep blood method, and RT-qPCR, respectively. Furthermore, we assessed the influence of dencichine on the lifespan of Caenorhabditis elegans. Results showed that dencichine was a suitable inhibitor of the Fn1220 of F. nucleatum, which significantly inhibited the production of virulence factors, e.g., biofilm, hemolysin, FadA, and Fap2 of F. nucleatum and improved the survival of C. elegans. We successfully identified the inhibitor of the enzyme Fn1220, dencichine, which inhibited the production of hydrogen sulfide and attenuated the virulence of F. nucleatum and holds promise as a potential therapeutic avenue for addressing oral diseases, e.g., halitosis in the future.

Characterization of Cetobacterium somerae CPU-CS01 isolated from the intestine of healthy crucian carp (Carassius auratus) as potential probiotics against Aeromonas hydrophila infection.

Cetobacterium somerae is a commensal bacterium for many fish species. However, research on C. somerae has been limited so far, and its function and beneficial potential require to be further investigated. The objective of this study was to evaluate the probiotic properties of C. somerae CPU-CS01 isolated from the intestinal contents of crucian carp (Carassius auratus). Hemolytic activity, antibiotic susceptibility, acid tolerance, bile salt tolerance, free radical scavenging, and enzyme production properties were tested for in vitro. Caenorhabditis elegans and zebrafish (Danio rerio) model were used to evaluate the antioxidant and anti-infective effects of C. somerae CPU-CS01 in vivo. Our results showed that C. somerae CPU-CS01 had no hemolytic activity, it produced cellulase, amylase, and survived at low pH (2.0-3.0) and in the presence of bile salts. The cell-free culture supernatant (CFCS) of C. somerae CPU-CS01 possessed DPPH radical, hydroxyl radical, and superoxide anion scavenging activity. C. elegans fed with C. somerae CPU-CS01 were more resistant to hydrogen peroxide-induced oxidative stress and Aeromonas hydrophila infection. In addition, zebrafish-fed diets containing C. somerae CPU-CS01 showed improved survival after A. hydrophila infection. Based on these results, the positive probiotic properties of C. somerae CPU-CS01 isolated from the intestinal contents of crucian carp make it a potential candidate for probiotic.

Alcohol degradation, learning, and memory-enhancing effect of Acetobacter pasteurianus BP2201 in Caenorhabditis elegans model.

AIMS: This study aimed to investigate the probiotic effects of Acetobacter pasteurianus BP2201, isolated from brewing mass, for the treatment of alcohol-induced learning and memory ability impairments in a Caenorhabditis elegans model. METHODS AND RESULTS: Acetobacter pasteurianus BP2201 was examined for probiotic properties, including acid and bile salt resistance, ethanol degradation, antioxidant efficacy, hemolytic activity, and susceptibility to antibiotics. The strain displayed robust acid and bile salt tolerance, efficient ethanol degradation, potent antioxidant activity, and susceptibility to specific antibiotics. Additionally, in the C. elegans model, administering A. pasteurianus BP2201 significantly improved alcohol-induced learning and memory impairments. CONCLUSIONS: Acetobacter pasteurianus BP2201 proves to be a promising candidate strain for the treatment of learning and memory impairments induced by alcohol intake.

Polystyrene nano/microplastics induce microbiota dysbiosis, oxidative damage, and innate immune disruption in zebrafish.

The toxicity of polystyrene nano/microplastics with diameter sizes of 50um and 100 nm and concentrations of 100 and 1000 µg/mL on gut microbiota, antioxidant activity and innate immune response in zebrafish was investigated. After exposure to polystyrene plastics particle, the pathological morphological changes of intestine and gills were observed, and the injury severity was related to the concentration and particle size of plastics. Significant changes in the richness and diversity of gut microbiota were observed after polystyrene plastics-exposed in zebrafish. The plastics-treated groups exhibited more substantial oxidative stress than the control group. In addition, the mRNA expression level of most pro- and anti-inflammatory factors, including IL-8, NF-κb, and IL-10, increased while the mRNA expression of TNF-α, a pro-inflammatory factor, decreased. Our results suggest that polystyrene nano/microplastics may represent a potential threat to the gut microbiota, oxidative status, and innate immunity. These results indicated that polystyrene nano/microplastics exerted size and concentration-dependent toxicity on zebrafish. The findings provide new evidence for the toxicity of polystyrene plastics on zebrafish.

SCFAs improve disease resistance via modulate gut microbiota, enhance immune response and increase antioxidative capacity in the host.

To evaluate the effects of dietary short chain fatty acids (SCFAs) on the intestinal health and innate immunity in crucian carp, a six-week feeding trial was carried out with following treatments: basal diet (BD), basal diet supplementation with 1% sodium acetate (BDSA), basal diet supplementation with 1% sodium propionate (BDSP) and basal diet supplementation with 1% sodium butyrate (BDSB). The results showed dietary BDSA, BDSP and BDSB could protect the host against oxidative stress by improving the activity of certain antioxidative enzymes (T-SOD, GSH-Px and CAT). Additionally, dietary SCFAs could enhance mucosal and humoral immune responses by improving certain innate immune parameters in serum and skin mucus productions (IgM, ACH50 and T-SOD). Furthermore, dietary BDSA and BDSP could up-regulate the expression of immune related genes (TNF-α, TGF-ß and IL-8) and tight junction protein genes (occludin and ZO-1). Dietary BDSB could also elevate the expression of IL-8, TGF-ß, ZO-1 and Occludin in the midgut. Although dietary differences of SCFAs didn't alter the α-diversity of the intestinal flora, they altered the core microbiota. Finally, the challenge trial showed that dietary basal diet supplementation with SCFAs could protect zebrafish against Aeromonas hydrophila. These results suggest that dietary SCFAs could improve innate immunity, modulate gut microbiota and increase disease resistance in the host, which indicated the potential of SCFAs as immunostimulants in aquaculture.

Exploring of probiotic potential vaginal lactobacillus isolates from healthy women against Gardnerella vaginalis and Caenorhabditis elegans model testing.

AIM: Lactobacillus species are the dominant microorganisms in the vaginal microbiota of healthy women and play an important role in the defence against pathogens. This study aimed to evaluate probiotic potential of Lactiplantibacillus plantarum strain P1 isolated from healthy woman's vaginal discharge for its further utilization as a promising candidate strain in the treatment of bacterial vaginosis caused by Gardnerella vaginalis. METHODS AND RESULTS: Ten lactobacilli strains from a woman's vaginal discharge were evaluated for their probiotic potential, including growth capacity at different pH levels (pH 3.5-4.5), acid production, hydrogen peroxide production capacity, antibacterial activity and susceptibility to antibiotics. Moreover, in vitro safety assay haemolytic activity and mutagenicity were investigated for safety assessment. In vivo Caenorhabditis elegans infection model was used to investigate the anti-infection effect of selected isolates. We found that lactobacilli strain P1 showed strong growth ability in low acid environment, produced acid, hydrogen peroxide, had the strongest antibacterial activity against G. vaginalis and was highly susceptible to the tested antibiotics. When assayed for the safety, strain P1 showed no haemolytic activity and had no effect of mutagenicity. Moreover, P1 significantly increased the lifespan of C. elegans against G. vaginalis infection. Combined with the results of 16S rRNA gene sequencing, morphological and physiological characteristic, the strain was identified as Lactiplantibacillus plantarum. CONCLUSION: Lactiplantibacillus plantarum strain P1 proves to be a promising candidate strain in the treatment of bacterial vaginosis caused by G. vaginalis. SIGNIFICANCE AND IMPACT OF THE STUDY: Conventional antibiotic therapy for bacterial vaginosis has led to the accelerated process of bacterial drug resistance. Probiotics are potentially an alternative method for bacterial vaginosis therapy. This finding provides bacterial resources for keeping pathogens away from the vagina. We believe L. plantarum P1 may be used as vaginal probiotics and be useful to prevent or treat bacterial vaginitis.

Influence of Fluconazole Administration on Gut Microbiome, Intestinal Barrier, and Immune Response in Mice.

Antibiotics that can treat or prevent infectious diseases play an important role in medical therapy. However, the use of antibiotics has potentially negative effects on the health of the host. For example, antibiotics use may affect the host's immune system by altering the gut microbiota. Therefore, the aim of the study was to investigate the influence of antifungal (fluconazole) treatment on the gut microbiota and immune system of mice. Results showed that the gut microbial composition of mice receiving fluconazole treatment was significantly changed after the trial. Fluconazole did not affect the relative abundance of bacteria but significantly reduced the diversity of bacterial flora. In the bacteriome, Firmicutes and Proteobacteria significantly increased, while Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes showed a remarkable reduction in the fluconazole-treated group compared with the control group. In the mycobiome, the relative abundance of Ascomycota was significantly decreased and Mucoromycota was significantly increased in the intestine of mice treated with fluconazole compared to the control group. Reverse transcription-quantitative PCR (RT-qPCR) results showed that the relative gene expression of ZO-1, occludin, MyD88, interleukin-1ß (IL-1ß), and IL-6 was decreased in the fluconazole-treated group compared to the control. Serum levels of IL-2, LZM, and IgM were significantly increased, while the IgG level was considerably downregulated in the fluconazole-treated compared to the control group. These results suggest that the administration of fluconazole can influence the gut microbiota and that a healthy gut microbiome is important for the regulation of the host immune responses.

Identification of choline-degrading bacteria from healthy human feces and used for screening of trimethylamine (TMA)-lyase inhibitors.

Gut microbiota-based choline metabolism produces trimethylamine (TMA), which is then further converted to the atherosclerosis-promoting metabolite trimethylamine-N-oxide (TMAO) by hepatic flavin-containing monooxygenases (FMOs) and TMAO plays an essential role in cardiovascular disease (CVD). Many Chinese herbal medicines had been used for the treatment of CVD. This study aimed to screen choline-degrading bacteria from healthy human feces and establish a platform in silico and in vitro approaches for screening TMA-lyase inhibitors from Chinese herbal medicines. Choline-degrading bacteria were screened from healthy human feces in basic salt medium using culture method. The isolated strains were identified as Klebsiella pneumoniae based on 16S rRNA and the presence of CutC gene. Structure of CutC choline lyase was obtained from the RCSB Protein Data Bank database, and the modeled structure was docked with natural compounds of Chinese herbal medicines origin using MOE. Further, we investigated the inhibitory effects of selected compounds by picric acid-toluene method using K. pneumoniae as bioassay indicator. We found that TMA level was significantly decreased when treated with ß-sitosterol and resveratrol. This study initially demonstrates the inhibitory effect of ß-sitosterol and resveratrol on the gut microbiota responsible for choline metabolism to TMA and sets up an inhibitor-screening platform for further experiments. It can be used as a model to evaluate herbal drug sources and their effects on the gut microbiota for cardiovascular disease.

Treatment of symptomatic Chiari I malformation by "all-factors-surgery": a report of 194 cases.

PURPOSE: Inadequate decompressions can lead to poor improvement of symptoms in patients with Chiari I malformation (CMI). In this study, the "all-factors-surgery" that including all levels decompressions was performed on symptomatic CMI patients for the snake of eliminating all possible pathogenic factors and reducing the chance of reoperation. METHODS: The "all-factors-surgery" combined operations of posterior fossa decompression, enlarged cranioplasty, duraplasty, cerebellar tonsil partial resection and adhesion release. Total 194 patients from January 2010 to December 2015. The outcome measures included improvement rate of symptoms, patients self-evaluation (improved, unchanged, worsened), Visual Analogue Scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Chicago Chiari Outcome Scale (CCOS) score, the diameter of the syrinx and complications. RESULTS: Postoperative data were collected from the three stages: at discharge, the short-term follow-up (average, 9.39 months), and the long-term follow-up (average, 54.44 months). Patients self-evaluation improvement rate in the three follow-up stages was 92.27%, 90.07% and 85.93%. The VAS scores (mean, 1.49, 1.21, 1.47 vs 3.76) and JOA scores (mean, 15.66, 15.99, 16.10 vs 14.84) were significant difference between the follow-up and pre-operation (P < .05). The CCOS scores of short-term and long-term follow-up were significantly better than that at discharge (mean, 14.75, 14.87 vs 13.68) (P < .05). The diameter of syrinx in each follow-up stage was significantly less than that in pre-operation (mean, 3.39, 1.95, 1.87 vs 5.09) (P < .05). There were no serious complications, and no one asked for reoperation during the follow up. CONCLUSION: Symptomatic CMI patients undergoing "all-factors-surgery" had persistently high rates of symptom relief and rarely needed reoperation.

Comparative proteomic analysis of sensitive and multi-drug resistant Aeromonas hydrophila isolated from diseased fish.

Bacterial hemorrhagic septicemia caused by multi-drug resistant (MDR) Aeromonas hydrophila has exponentially increased in the past decade, and reached an alarming rate making it a major concern in the aquaculture industry in China. The aim of this study was to investigate the difference in the regulation of proteins expression in multi-drug resistance and susceptible A. hydrophila strains isolated from diseased fish using two-dimensional electrophoresis (2-DE) combined with mass spectrometry. 28 isolates of A. hydrophila were successfully identified by biochemical tests. Antibiotic susceptibility test results showed that all the isolates have different drug resistant patterns. A total of 61 and 17 differently expressed proteins were identified in MDR and susceptible A. hydrophila, respectively, evidencing that biological processes related to carbon metabolism, biosynthesis of secondary metabolites, microbial metabolism in diverse environments, cationic antimicrobial peptide (CAMP) resistance and propanoate metabolism were down-regulated in MDR strain, while proteins involved in biosynthesis of antibiotics, glycolysis/gluconeogenesis were highly expressed in the sensitive strain. The analysis of differentially expressed proteins from multi-drug resistance and susceptible strains suggests that a number of proteins are involved in several metabolic metabolism pathways plays an important role in A. hydrophila drug resistance. Our findings provide new insights about mechanisms involved in drug resistance and propose possible novel targets for developing alternative antibacterial drugs.

Isolation and preliminary screening of potentially probiotic Weissella confusa strains from healthy human feces by culturomics.

PURPOSE: The objective of this study was to isolate and identify strains of bacteria from feces of healthy human and screen potential probiotic candidate by using culturomics method combined with the matrix-assisted laser desorption/ionization-time of flight mass spectrum (MALDI-TOF MS) and 16S rRNA gene sequencing. METHODS AND RESULTS: 31 strains were isolated and purified from human feces by culturomics method, and identified by MALDI-TOF MS and 16S rRNA gene sequencing. Then the obtained strains were tested for haemolytic activity, antibiotic susceptibility, acid and bile salts tolerance, antimicrobial activity, morphological and physiological characteristics. Three potential probiotic candidate strains named YM5Y, YM5S1 and YM5S2 were selected and identified as Weissella confusa. CONCLUSION: Our results suggest the culturomics approach could be used to isolate and screen human fecal strains which could eventually be used for the development of novel probiotics. In addition, the isolated strains of W. confusa can act as potential probiotics and should be explored further for their potential application.

The effect of Bailemian on neurotransmitters and gut microbiota in p-chlorophenylalanine induced insomnia mice.

Bailemian (BLM) is reportedly used for the treatment of insomnia as a traditional Chinese medicine in China for many years. However, the anti-insomnia mechanisms of BLM are still unknown. The present study aims to investigate the anti-insomnia activity of BLM by evaluating its influence on the relevant neurotransmitters and gut microbiota in p-chlorophenylalanine (PCPA) induced insomnia mice. The results indicated that the level of GABA, 5-HT, DA, and NE is significantly decreased in the PCPA-induced insomnia model group compared with the control group, while the level of Glu is higher than the control group. Treatment with BLM could ameliorate the symptoms of insomnia and significantly modulate the levels of the neurotransmitters mentioned above in brain and colonic faeces. Furthermore, the structure and composition of gut microbiota were changed after the administration of BLM and can increase the percentage of beneficial bacterial species in gut microbiota. These results indicated that Bailemian could ameliorate the symptoms of insomnia, and its effects may be through modification of the neurotransmitters levels and gut microbiota composition.

Tea polyphenols inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances resistance to Klebsiella pneumoniae infection in Caenorhabditis elegans model.

Bacteria cells can communicate with each other via quorum sensing (QS) system. Various physiological characteristics including virulence factors and biofilm formation are controlled by QS. So interrupting the bacterial communication is an alternative strategy instead of antibiotics for control bacterial infection. The aim of this study was to investigate the effects of tea polyphenols (TPs) on quorum sensing and virulence factors of Klebsiella pneumoniae. In vitro study showed that the anti-QS activity of tea polyphenols against Chromobacterium violaceum in violacein production. At sub-MICs, TPs inhibited the motility, reduced protease and exopolysaccharide (EPS) production and also biofilm formation in K. pneumoniae. In addition, in vivo study showed that tea polyphenols at 200 µg/mL and 400 µg/mL increased the survival rate of Caenorhabditis elegans to 73.3% and 82.2% against K. pneumonia infection. Our findings suggest that tea polyphenols can act as an effective QS inhibitor and can serve as a novel anti-virulence agent for the management of bacterial pathogens.

Shifts in the gut microbiota of mice in response to dexamethasone administration.

Glucocorticoids (GCs) are an important anti-inflammatory drug, used widely, regardless of its side effects. GCs can affect intestinal flora directly or indirectly, though few studies have focused on the changes of gut microbiota composition. In this study, ICR mice were randomly divided into three groups, gavage administration with saline, and different doses of dexamethasone (DEX): 0.1 mg/kg and 1 mg/kg. Five days later, the microbial diversity of the colon contents was analyzed. A significant loss in weight was observed in the DEX1.0 group as compared with the control group (P = 0.011). The gut microbiota richness (ACE, P = 0.01; Chao, P = 0.013) and diversity (Shannon, P = 0.035; Simpson, P = 0.032) were decreased in DEX group. The proportions of genus Butyricicoccus, Oscillibacter, Anaerotruncus, Ruminiclostridium, Ruminococcaceae, and Lachnospiraceae were the most abundant and predominant followed by Lactobacillus, Pseudomonas, and Enterorhabdus. Dex administration led to changes in the liver/body ratio and spleen/body ratio. The results obtained from our study indicate that DEX can decrease the level of WBC and change the structure of the gut microbiota composition; moreover, the results of this study provide new insight into alleviating the clinical side effects of GC therapy.

Anti-quorum sensing activity of Forsythia suspense extract against Chromobacterium violaceum by targeting CviR receptor.

The increasing incidence of antimicrobial-resistant bacterial pathogens has focused researchers on quorum sensing inhibition strategies instead of those conventional approaches to fight bacterial infections. Anti-quorum sensing (QS) activity of aqueous extract from Forsythia suspense (FSE) was assessed, and its potential QS inhibition mechanisms were also analyzed. The minimal inhibitory concentration (MIC) of FSE to Chromobacterium violaceum 12472 is 0.5 mg mL-1. Inhibition of QS-regulated violacein production and biofilm formation in C. violaceum 12472 by FSE occurred in a concentration-dependent manner at sub-MIC, with > 70.12 and > 85.31% inhibition at 0.25 mg mL-1, respectively. N-Acyl homoserine lactones (AHLs) extracted from cultures of C. violaceum 31532 grown in the presence of FSE could not change the violacein production in C. violaceum 026, which indicated that FSE did not inhibit AHL synthesis. We also found that FSE cannot degrade AHLs. Finally, in silico molecular docking was conducted. The computed binding energy data suggested that components of F. suspense have a tendency to inhibit CviR with varying binding affinities and the energy score of Pinoresinol (- 26.02 kcal/mol) is higher than that of C6-HSL (- 16.09 kcal mol-1). We concluded that FSE acts as an antagonist of bacterial quorum sensing by competing with AHL receptor binding site.

Risk factor analysis for progressive spinal deformity after resection of intracanal tumors─ a retrospective study of 272 cases.

BACKGROUND: Progressive spinal deformity has become a well-recognized complication of intracanal tumors resection. However, the factors affecting post-operative spinal stability remain to be further research. Here, we described the current largest series of risk factors analysis for progressive spinal deformity following resection of intracanal tumors. METHODS: We retrospectively analyzed the medical records of the patients with resection of intracanal tumors between January 2009 and December 2018. All patients who underwent resection of intracanal tumors performed regular postoperative follow-up were identified and included in the study. Clinical, radiological, surgical, histopathological, and follow-up data were collected. The incidence of postoperative progressive kyphosis or scoliosis was calculated. The statistical relationship between postoperative progressive spinal deformity and radiographic, clinical, and surgical variables was assessed by using univariate tests and multivariate logistic regression analysis. RESULTS: Two hundred seventy-two patients (mean age 42.56 ± 16.18 years) with median preoperative modified McCormick score of 3 met the inclusion criteria. Among them, 7(2.6%)patients were found to have spinal deformity preoperatively, and the extent of spinal deformity in these 7 patients deteriorated after surgery. 36 (13.2%) were new cases of postoperative progressive deformity. The mean duration of follow-up was 21.8 months (median 14 months, range 6-114 months). In subsequent multivariate logistic regression analysis, age ≤ 18 years (p = 0.027), vertebral levels of tumor involvement (p = 0.019) and preoperative spinal deformity(p = 0.008) was the independent risk factors (p < 0.05), increasing the odds of postoperative progressive spinal deformity by 3.94-, 0.69- and 27.11-fold, respectively. CONCLUSIONS: The incidence of postoperative progressive spinal deformity was 15.8%, mostly in these patients who had younger age (≤18 years), tumors involved in multiple segments and preoperative spinal deformity. The risk factors of postoperative progressive spinal deformity warrants serious reconsideration that when performing resection of spinal cord tumors in these patients with such risk factors, the surgeons should consider conducting follow-ups more closely, and when patients suffering from severe symptoms or gradually increased spinal deformity, surgical spinal fusion may be a more suitable choice to reduce the risk of reoperation and improve the prognosis of patients.

Effect of quorum-quenching bacterium Bacillus sp. QSI-1 on protein profiles and extracellular enzymatic activities of Aeromonas hydrophila YJ-1.

BACKGROUND: In natural environments, bacteria always live in communities with others where their physiological characteristics are influenced by each other. Bacteria can communicate with one another by using autoinducers. The current knowledge on the effect of quenching bacteria on others is limited to assess the impact of quorum-quenching bacterium Bacillus sp. QSI-1 on proteins pattern and virulence factors production of Aeromonas hydrophila YJ-1. Proteomic analysis was performed to find out protein changes and virulence factors, after 24 h co-culture. RESULTS: Results showed that several proteins of A. hydrophila YJ-1 were altered, seventy-two differentially expressed protein spots were excised from 2-DE gels and analyzed by MALDI-TOF/TOF MS, resulting in 63 individual proteins being clearly identified from 70 spots. Among these proteins, 50 were divided into 22 classes and mapped onto 18 biological pathways. Mixed-culture growth with Bacillus sp. QSI-1 resulted in an increase of A. hydrophilia proteins involved in RNA polymerase activity, biosynthesis of secondary metabolites, flagellar assembly, and two-component systems. In contrast, mixed culture resulted in a decreased level of proteins involved in thiamine metabolism; valine, leucine and isoleucine biosynthesis; pantothenate and CoA biosynthesis. In addition, the two extracellular virulence factors, proteases and hemolysin, were significantly reduced when A. hydrophila was co-cultured with QSI-1, while only lipase activity was observed to increase. CONCLUSIONS: The information gathered from our experiment showed that Bacillus sp. QSI-1 has a major impact on the expression of proteins, including virulence factors of A. hydrophila.

Influences of stress hormones on microbial infections.

Stress hormones have been recently suggested to influence the pathogenicity of bacteria significantly. Stress has been identified as part of the factors causing an outbreak of infections in the aquaculture industry. The most studied neuroendocrine hormonal family from a microbial endocrinology perspective is the catecholamine comprising of norepinephrine, epinephrine, and dopamine. It is of importance that catecholamine affects the growth and virulence of bacteria. The influence of stress on bacterial infections is attributed to the ability of catecholamines to suppress the immune system as the mode of action for increased bacterial growth. Catecholamines have increased the growth of bacteria, virulence-associated factors, adhesions, and biofilm formation and consequently influence the outcome of infections by these bacteria in many hosts. The siderophores and the ferric iron transport system plays a vital role in the mechanism by which catecholamines stimulates growth and exposure of genes to stress hormones enhances the expression of genes involved in bacterial virulence. In recent years, it has been discovered that intestinal microflora takes part in bidirectional communication between the gut and brain. The rapidly growing field of microbiome research, understanding the communities of bacteria living within our bodies and the genes they contain is yielding new perspectives. This review reveals catecholamines effects on the growth and virulence of bacteria and the latest trends in microbial endocrinology.

The effects of dietary Bacillus cereus QSI-1 on skin mucus proteins profile and immune response in Crucian Carp (Carassius auratus gibelio).

The objective of this study was to investigate the effect of dietary quorum quenching bacterium Bacillus cereus QSI-1 on skin mucus protein pattern and innate immune response in Crucian Carp (Carassius auratus gibelio). The differential proteomes of skin mucus of Crucian Carp were analyzed after administration of Bacillus cereus QSI-1 by isobaric tags for relative and absolute quantitation (iTRAQ) labeling, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1974 proteins were quantified. Using a 1.5-fold change in expression as a physiological significant benchmark, 264 differentially expressed proteins were reliably quantified by iTRAQ analysis, including 130 up- and 134 down-regulated proteins after dietary Bacillus cereus QSI-1. Some Proteins that were involved in immunity included protein S100, annexin, histone H3, lymphocyte cytosolic protein 1, heat shock protein, L-plastin, keratin 91, etc. Furthermore, fish fed 5 × 108 CFU/g Bacillus cereus QSI-1 supplemented diet showed an increase in alternative complement activity and lysozyme activity but expressed a decrease in superoxide dismutase activity in skin mucus (P < 0.05). However, administration of Bacillus cereus QSI-1 had no significant effects on total immunoglobulin level (P > 0.05). These results demonstrated that dietary administration of Bacillus cereus QSI-1 affects skin mucus protein profile and innate immune response in Crucian Carp, and also can enhance the disease resistance of Crucian Carp against A. hydrophila. This is the first report on proteomics analysis of skin mucus proteins in Crucian Carp after administration of quorum quenching bacterium Bacillus cereus, and the results will help to understand the mucosal immune responses to probiotics at the protein level in fish.

Chlorogenic acid attenuates virulence factors and pathogenicity of Pseudomonas aeruginosa by regulating quorum sensing.

Quorum sensing (QS) is a cell-to-cell communication that is used by bacteria to regulate collective behaviors. Quorum sensing controls virulence factor production in many bacterial species and it is regarded as an attractive target to combat bacterial pathogenicity, especially against antibiotic-resistant bacteria. Chlorogenic acid (CA), abundant in fruits, vegetables, and Chinese herbs, processes multiple activities. In this research, we explored its quorum sensing quenching activity. In Pseudomonas aeruginosa, CA significantly inhibited the formation of biofilm, the ability of swarming, and virulence factors including protease and elastase activities and rhamnolipid and pyocyanin production. CA showed similar inhibitory effects in Chromobacterium violaceum on its biofilm formation, swarming motility, chitinolytic activity and violacein production. We examined the expression of QS-related genes in P.aeruginosa  and found these genes were all downregulated by CA treatment. Computational modeling revealed that CA can form hydrogen bonds with all three QS receptors. Caenorhabditis elegans and mouse infection models were employed to explore the anti-virulence ability of CA and its effect on pathogenesis process in vivo. CA extended the survival period and reduced the quantity of P. aeruginosa in nematode gut, showing a moderate protective effect on C. elegans. In mice wound model, CA-treated groups showed an accelerating healing rate and the bacteria number in wound area was also decreased by CA treatment. It is suggested by our research that CA has potential to be used as an anti-virulence factor in P. aeruginosa infection.