Human gut is in permanent contact with microorganisms that play an important role in many physiological processes including metabolism and immunologic activity. These microorganisms communicate and manage themself by the quorum sensing system (QS) that helps to coordinate optimal growth and subsistence by activating signaling pathways that regulate bacterial gene expression. Diverse QS molecules produced by pathogenic as well as resident microbiota have been found throughout the human gut. However, even a host can by affected by these molecules. Intestinal and immune cells possess a range of molecular targets for QS. Our present knowledge on bacteria-cell communication encompasses G-protein-coupled receptors, nuclear receptors and receptors for bacterial cell-wall components. The QS of commensal bacteria has been approved as a protective factor with favourable effects on intestinal homeostasis and immunity. Signaling molecules of QS interacting with above-mentioned receptors thus parcipitate on maintaining of barrier functions, control of inflammation processes and increase of resistance to pathogen colonization in host organisms. Pathogens QS molecules can have a dual function. Host cells are able to detect the ongoing infection by monitoring the presence and changes in concentrations of QS molecules. Such information can help to set the most effective immune defence to prevent or overcome the infection. Contrary, pathogens QS signals can target the host receptors to deceive the immune system to get the best conditions for growth. However, our knowledge about communication mediated by QS is still limited and detailed understanding of molecular mechanisms of QS signaling is desired.
- Keywords
- G protein-coupled receptors, Indole, N-Acyl-homoserine lactone, Nuclear receptors, Quorum sensing system,
- MeSH
- Bacteria metabolism MeSH
- Humans MeSH
- Quorum Sensing * MeSH
- Signal Transduction * MeSH
- Intestines parasitology MeSH
- Gastrointestinal Microbiome * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Marine sponges, a well-documented prolific source of natural products, harbor highly diverse microbial communities. Their extracts were previously shown to contain quorum sensing (QS) signal molecules of the N-acyl homoserine lactone (AHL) type, known to orchestrate bacterial gene regulation. Some bacteria and eukaryotic organisms are known to produce molecules that can interfere with QS signaling, thus affecting microbial genetic regulation and function. In the present study, we established the production of both QS signal molecules as well as QS inhibitory (QSI) molecules in the sponge species Sarcotragus spinosulus. A total of eighteen saturated acyl chain AHLs were identified along with six unsaturated acyl chain AHLs. Bioassay-guided purification led to the isolation of two brominated metabolites with QSI activity. The structures of these compounds were elucidated by comparative spectral analysis of 1HNMR and HR-MS data and were identified as 3-bromo-4-methoxyphenethylamine (1) and 5,6-dibromo-N,N-dimethyltryptamine (2). The QSI activity of compounds 1 and 2 was evaluated using reporter gene assays for long- and short-chain AHL signals (Escherichia coli pSB1075 and E. coli pSB401, respectively). QSI activity was further confirmed by measuring dose-dependent inhibition of proteolytic activity and pyocyanin production in Pseudomonas aeruginosa PAO1. The obtained results show the coexistence of QS and QSI in S. spinosulus, a complex signal network that may mediate the orchestrated function of the microbiome within the sponge holobiont.
- Keywords
- 3-bromo-4-methoxyphenethylamine, 5,6-dibromo-N,N-dimethyltryptamine, N-acyl homoserine lactone, Sarcotragus spinosulus, quorum sensing, quorum sensing inhibition, sponge,
- MeSH
- Escherichia coli drug effects physiology MeSH
- Virulence Factors MeSH
- Phylogeny MeSH
- Luminescent Measurements MeSH
- Porifera genetics metabolism microbiology MeSH
- Peptide Hydrolases chemistry pharmacology MeSH
- Pyocyanine chemistry pharmacology MeSH
- Quorum Sensing drug effects MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Virulence Factors MeSH
- Peptide Hydrolases MeSH
- Pyocyanine MeSH
The regulation of the production of oligopeptides is essential in understanding their ecological role in complex microbial communities, including harmful cyanobacterial blooms. The role of chemical communication between the cyanobacterium and the microbial community harbored as epibionts within its phycosphere is at an initial stage of research, and little is understood about its specificity. Here, we present insight into the role of a bacterial epibiont in regulating the production of novel microviridins isolated from Nostoc, an ecologically important cyanobacterial genus. Microviridins are well-known elastase inhibitors with presumed antigrazing effects. Heterologous expression and identification of specific signal molecules from the epibiont suggest the role of a quorum-sensing-based interaction. Furthermore, physiological experiments show an increase in microviridin production without affecting cyanobacterial growth and photosynthetic activity. Simultaneously, oligopeptides presenting a selective inhibition pattern provide support for their specific function in response to the presence of cohabitant epibionts. Thus, the chemical interaction revealed in our study provides an example of an interspecies signaling pathway monitoring the bacterial flora around the cyanobacterial filaments and the induction of intrinsic species-specific metabolic responses. IMPORTANCE The regulation of the production of cyanopeptides beyond microcystin is essential to understand their ecological role in complex microbial communities, e.g., harmful cyanobacterial blooms. The role of chemical communication between the cyanobacterium and the epibionts within its phycosphere is at an initial stage of research, and little is understood about its specificity. The frequency of cyanopeptide occurrence also demonstrates the need to understand the contribution of cyanobacterial peptides to the overall biological impact of cyanopeptides on aquatic organisms and vertebrates, including humans. Our results shed light on the epibiont control of microviridin production via quorum-sensing mechanisms, and we posit that such mechanisms may be widespread in natural cyanobacterial bloom community regulation.
- Keywords
- cyanobacteria, cyanopeptides, homoserine lactones, microviridin, quorum sensing,
- MeSH
- Peptides, Cyclic genetics metabolism MeSH
- Genome, Bacterial MeSH
- Microcystins genetics metabolism MeSH
- Nostoc genetics metabolism MeSH
- Quorum Sensing genetics physiology MeSH
- Fresh Water microbiology MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Peptides, Cyclic MeSH
- microcystin MeSH Browser
- Microcystins MeSH
Lactobacillus plantarum NMD-17 separated from koumiss could produce a bacteriocin named plantaricin MX against Gram-positive bacteria and Gram-negative bacteria. The bacteriocin synthesis of L. plantarum NMD-17 was remarkably induced in co-cultivation with Lactobacillus reuteri NMD-86 as the increase of cell numbers and AI-2 activity, and the expressions of luxS encoding signal AI-2 synthetase, plnB encoding histidine protein kinase, plnD encoding response regulator, and plnE and plnF encoding structural genes of bacteriocin were significantly upregulated in co-cultivation, showing that the bacteriocin synthesis of L. plantarum NMD-17 in co-cultivation may be regulated by LuxS/AI-2-mediated quorum sensing system. In order to further demonstrate the role of LuxS/AI-2-mediated quorum sensing system in the bacteriocin synthesis of L. plantarum NMD-17, plasmids pUC18 and pMD18-T simple were used as the skeleton to construct the suicide plasmids pUC18-UF-tet-DF and pMD18-T simple-plnB-tet-plnD for luxS and plnB-plnD gene deletion, respectively. luxS and plnB-plnD gene knockout mutants were successfully obtained by homologous recombination. luxS gene knockout mutant lost its AI-2 synthesis ability, suggesting that LuxS protein encoded by luxS gene is key enzyme for AI-2 synthesis. plnB-plnD gene knockout mutant lost the ability to synthesize bacteriocin against Salmonella typhimurium ATCC14028, indicating that plnB-plnD gene was a necessary gene for bacteriocin synthesis of L. plantarum NMD-17. Bacteriocin synthesis, cell numbers, and AI-2 activity of luxS or plnB-plnD gene knockout mutants in co-cultivation with L. reuteri NMD-86 were obviously lower than those of wild-type strain in co-cultivation at 6-9 h (P < 0.01). The results showed that LuxS/AI-2-mediated quorum sensing system played an important role in the bacteriocin synthesis of L. plantarum NMD-17 in co-cultivation.
- Keywords
- Bacteriocin, Co-cultivation, Gene knockout, Lactobacillus plantarum, LuxS-mediated quorum sensing system,
- MeSH
- Bacterial Proteins metabolism MeSH
- Bacteriocins * metabolism MeSH
- Lactobacillus plantarum * genetics MeSH
- Lactobacillus physiology MeSH
- Humans MeSH
- Plasmids MeSH
- Quorum Sensing MeSH
- Gene Expression Regulation, Bacterial MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Bacterial Proteins MeSH
- Bacteriocins * MeSH
The influence of basis of quorum sensing molecules on Proteus strains is much less known as compared to Pseudomonas or Escherichia. We have previously shown that a series of acylated homoserine lactones (acyl-HSL) does not influence the ureolytic, proteolytic, or hemolytic abilities, and that the swarming motility of Proteus mirabilis rods is strain specific. The aim of the presented study was to find out if the presence of a series of acyl-HSL influences biofilm formation of P. mirabilis laboratory strain belonging to O18 serogroup. This serogroup is characterized by the presence of a unique non-carbohydrate component, namely phosphocholine. Escherichia coli and P. mirabilis O18 strains used in this work contains cloned plasmids encoding fluorescent protein genes with constitutive gene expression. In mixed biofilms in stationary and continuous flow conditions, P. mirabilis O18 overgrow whole culture. P. mirabilis O18 strain has genetically proved a presence of AI-2 quorum sensing system. Differences in biofilm structure were observed depending on the biofilm type and culture methods. From tested acylated homoserine lactones (BHL, HHL, OHL, DHL, dDHL, tDHL), a significant influence had BHL on thickness, structure, and the amount of exopolysaccharides produced by biofilms formed by P. mirabilis O18 pDsRed(2).
- MeSH
- Acyl-Butyrolactones chemistry metabolism MeSH
- Bacterial Proteins genetics metabolism MeSH
- Biofilms * MeSH
- Molecular Structure MeSH
- Proteus mirabilis chemistry genetics physiology MeSH
- Quorum Sensing * MeSH
- Gene Expression Regulation, Bacterial MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acyl-Butyrolactones MeSH
- Bacterial Proteins MeSH
Developing methods to sense local variations in properties of nearby materials, such as their refractive index and thickness, are important in numerous fields including chemistry and biomedical applications. Localized surface plasmons (LSPs) excited in plasmonic nanostructures have been demonstrated to be useful in this context due to the spectral location of their associated resonances being sensitive to changes in the environment near the plasmonic structures. This manuscript explores Babinet's principle by exploiting LSP resonances excited in complementary metal-dielectric cylindrical plasmonic structures (plasmonic particle-dimers and aperture-dimers in our case). Both plasmonic structures are evaluated numerically and experimentally using electron energy loss spectroscopy (EELS), providing a full physical understanding of the complementary nature of the excited LSP resonances. These plasmonic structures are then exploited for dielectric sensing under two configurations: when a thin dielectric film is positioned atop the plasmonic structures and when the analyte surrounds/fills the plasmonic particles/apertures. The complementary sensing performance of both proposed structures is also evaluated, showing the approximate validity of the Babinet principle with sensitivity values of up to ∼650 nm/RIU for thin dielectric sensing.
- Keywords
- Babinet, dielectric sensing, nanoantennas, nanoparticles, plasmonic dimers, plasmonics,
- Publication type
- Journal Article MeSH
OBJECTIVE: Autosomal dominant hypocalcemia (ADH) is a rare disorder caused by activating mutations of the calcium-sensing receptor (CASR). The treatment of ADH patients with 1α-hydroxylated vitamin D derivatives can cause hypercalciuria leading to nephrocalcinosis. DESIGN AND METHODS: We studied a girl who presented with hypoparathyroidism and asymptomatic hypocalcemia at age 2.5 years. Mutations of CASR were investigated by DNA sequencing. Functional analyses of mutant and WT CASRs were done in transiently transfected human embryonic kidney (HEK293) cells. RESULTS: The proband and her father are heterozygous for an eight-nucleotide deletion c.2703_2710delCCTTGGAG in the CASR encoding the intracellular domain of the protein. Transient expression of CASR constructs in kidney cells in vitro suggested greater cell surface expression of the mutant receptor with a left-shifted extracellular calcium dose-response curve relative to that of the WT receptor consistent with gain of function. Initial treatment of the patient with calcitriol led to increased urinary calcium excretion. Evaluation for mosaicism in the paternal grandparents of the proband was negative. CONCLUSIONS: We describe a novel naturally occurring deletion mutation within the CASR that apparently arose de novo in the father of the ADH proband. Functional analysis suggests that the cytoplasmic tail of the CASR contains determinants that regulate the attenuation of signal transduction. Early molecular analysis of the CASR gene in patients with isolated idiopathic hypoparathyroidism is recommended because of its relevance to clinical outcome and treatment choice. In ADH patients, calcium supplementation and low-dose cholecalciferol avoids hypocalcemic symptoms without compromising renal function.
- MeSH
- Cytoplasm MeSH
- Genes, Dominant * MeSH
- Adult MeSH
- HEK293 Cells MeSH
- Heterozygote MeSH
- Hypercalciuria genetics pathology MeSH
- Hypocalcemia genetics pathology MeSH
- Hypoparathyroidism congenital genetics pathology MeSH
- Humans MeSH
- Codon, Nonsense genetics MeSH
- Child, Preschool MeSH
- Receptors, Calcium-Sensing chemistry genetics MeSH
- Family MeSH
- Pedigree MeSH
- Base Sequence MeSH
- Sequence Deletion * MeSH
- Protein Structure, Tertiary genetics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Codon, Nonsense MeSH
- Receptors, Calcium-Sensing MeSH
Pleiotropic drug resistance (PDR) transporters play essential roles in cell resistance to various toxic compounds in various organisms including bacteria, mammals and yeasts. A large group of PDR transporters have been described in yeasts so far, including those that are controlled by transcription factor Pdr1p. Here, we show that besides their role in removing extracellularly added toxic compounds, the Pdr5p and Snq2p transporters play important physiological roles and significantly influence the developmental phases and physiology of yeast populations growing in a liquid culture. They appear to be involved in population quorum sensing, which consequently influences transcription factor Pdr1p level via feedback regulation.
- MeSH
- ATP-Binding Cassette Transporters genetics metabolism MeSH
- DNA-Binding Proteins MeSH
- Quorum Sensing physiology MeSH
- Saccharomyces cerevisiae Proteins genetics metabolism MeSH
- Saccharomyces cerevisiae genetics metabolism MeSH
- Trans-Activators genetics metabolism MeSH
- Transcription Factors MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ATP-Binding Cassette Transporters MeSH
- DNA-Binding Proteins MeSH
- PDR1 protein, S cerevisiae MeSH Browser
- PDR5 protein, S cerevisiae MeSH Browser
- Saccharomyces cerevisiae Proteins MeSH
- SNQ2 protein, S cerevisiae MeSH Browser
- Trans-Activators MeSH
- Transcription Factors MeSH
BACKGROUND/AIMS: Calcium-Sensing Receptor (CaSR) significantly affects calcium-phosphate metabolism in kidneys, and it is implicated in the pathogenesis of diabetes mellitus (DM) due to its expression in pancreatic β-cells. The role of CaSR as one of the players in pathogenesis of chronic kidney disease (CKD) has been speculated. METHODS: 158 Type 2 diabetic patients divided into three groups according to occurrence and type of kidney complications, 66 nondiabetic patients CKD, and 93 healthy subjects were enrolled into the study to analyze the role of two CaSR polymorphisms (in the codon 990 and in the intron 4) in ethiopathogenesis of DM and CKD. The Type 2 diabetic groups consisted of 48 patients without any kidney abnormalities, 58 patients with diabetic nephropathy (DN), and 52 patients with nondiabetic renal disease (NDRD). The distribution of genotype and allele frequencies was studied using PCR with the TaqMan Discrimination Assay or followed by the Restriction Fragment Length Polymorphism method, respectively. RESULTS: We have found that the intron 4 polymorphism is a risk factor for the development of DM and CKD, except DN, while the codon 990 does not show any disease association. CONCLUSION: We conclude that CaSR is a general factor in pancreas and kidney pathologies.
- MeSH
- Chronic Disease MeSH
- Diabetes Mellitus, Type 2 diagnosis genetics MeSH
- Diabetic Nephropathies diagnosis genetics MeSH
- Adult MeSH
- Introns genetics MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Diabetes Complications diagnosis genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Kidney Diseases diagnosis genetics MeSH
- Receptors, Calcium-Sensing genetics MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- CASR protein, human MeSH Browser
- Receptors, Calcium-Sensing MeSH
OBJECTIVE: High extracellular calcium concentration (Cao(2+)) acts to inhibit calcium sensing receptor (CaR) signalling on cellular surfaces in parathyroid glands. This receptor is, however, also expressed on the membranes of some non-calciotropic endocrine cells, including pituitary-derived cells. The aim of our study was to analyse relationships between the CaR gene and the circulating FSH and LH in normal post-menopausal women. METHODS: A total of 95 untreated euparathyroid post-menopausal women were investigated in the study. The serum FSH and LH levels were evaluated in relationship to allele combinations of the CaR gene (C/T polymorphism in the intron 5 and A986S polymorphism in exon 7), using an analysis of co-variance (ANCOVA) model. RESULTS: Distribution of TT, TC and CC allele combinations (intron 5 C/T polymorphism) was 51, 43 and 6 %, respectively. Higher serum FSH and LH levels were found in carriers of C allele than in women without this allele (p < 0.002 and p < 0.03, respectively). No correlations were found between A986S polymorphism and serum FSH and LH levels. CONCLUSIONS: Serum FSH and LH levels are associated with intron 5 C/T (but not A986S) polymorphism of the CaR gene in untreated post-menopausal women. The physiological role of the CaR gene in the regulation of the gonadotropic function needs to be further investigated.
- MeSH
- Alleles MeSH
- Adult MeSH
- Follicle Stimulating Hormone blood MeSH
- Genotype MeSH
- Introns * MeSH
- Humans MeSH
- Luteinizing Hormone blood MeSH
- Polymorphism, Genetic * MeSH
- Postmenopause * MeSH
- Cross-Sectional Studies MeSH
- Receptors, Calcium-Sensing genetics metabolism MeSH
- Statistics as Topic MeSH
- Calcium metabolism MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Follicle Stimulating Hormone MeSH
- Luteinizing Hormone MeSH
- Receptors, Calcium-Sensing MeSH
- Calcium MeSH
