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Microbiology Spectrum Aug 2022Burkholderia cenocepacia is a human opportunistic pathogen that mostly employs two types of quorum-sensing (QS) systems to regulate its various biological functions and...
Burkholderia cenocepacia is a human opportunistic pathogen that mostly employs two types of quorum-sensing (QS) systems to regulate its various biological functions and pathogenicity: the -2-dodecenoic acid (BDSF) system and the -acyl homoserine lactone (AHL) system. In this study, we reported that oridonin, which was screened from a collection of natural products, disrupted important B. cenocepacia phenotypes, including motility, biofilm formation, protease production, and virulence. Genetic and biochemical analyses showed that oridonin inhibited the production of BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Furthermore, we revealed that oridonin directly binds to the regulator RqpR of the two-component system RqpSR that dominates the above-mentioned QS systems to inhibit the expression of the BDSF and AHL signal synthase-encoding genes. Oridonin also binds to the transcriptional regulator CepR of the AHL system to inhibit its binding to the promoter of . These findings suggest that oridonin could potentially be developed as a new QS inhibitor against pathogenic B. cenocepacia. Burkholderia cenocepacia is an important human opportunistic pathogen that can cause life-threatening infections in susceptible individuals. It employs quorum-sensing (QS) systems to regulate biological functions and virulence. In this study, we have identified a lead compound, oridonin, that is capable of interfering with B. cenocepacia QS signaling and physiology. We demonstrate that oridonin suppressed -2-dodecenoic acid (BDSF) and -acyl homoserine lactone (AHL) signal production and attenuated virulence in B. cenocepacia. Oridonin also impaired QS-regulated phenotypes in various Burkholderia species. These results suggest that oridonin could interfere with QS signaling in many Burkholderia species and might be developed as a new antibacterial agent.
Topics: Acyl-Butyrolactones; Bacterial Proteins; Burkholderia cenocepacia; Diterpenes, Kaurane; Gene Expression Regulation, Bacterial; Humans; Quorum Sensing; Virulence
PubMed: 35856676
DOI: 10.1128/spectrum.01787-22 -
Applied and Environmental Microbiology Feb 2022It has been demonstrated that quorum sensing (QS) is widely employed by bacterial cells to coordinately regulate various group behaviors. Diffusible signal factor... (Review)
Review
It has been demonstrated that quorum sensing (QS) is widely employed by bacterial cells to coordinately regulate various group behaviors. Diffusible signal factor (DSF)-type signals have emerged as a growing family of conserved cell-cell communication signals. In addition to the DSF signal initially identified in Xanthomonas campestris pv. campestris, iffusible ignal actor (BDSF) (-2-dodecenoic acid) has been recognized as a conserved DSF-type signal with specific characteristics in both signal perception and transduction from DSF signals. Here, we review the history and current progress of the research on this type of signal, especially focusing on its biosynthesis, signaling pathways, and biological functions. We also discuss and explore the huge potential of targeting this kind of QS system as a new therapeutic strategy to control bacterial infections and diseases.
Topics: Bacterial Proteins; Burkholderia; Burkholderia cenocepacia; Fatty Acids, Monounsaturated; Gene Expression Regulation, Bacterial; Quorum Sensing; Suppressor Factors, Immunologic
PubMed: 34985987
DOI: 10.1128/aem.02342-21 -
Molecules (Basel, Switzerland) Dec 2021Pork lard (PL) is traditionally used as an anti-inflammatory agent. We propose to demonstrate the anti-inflammatory properties of PL, and elucidate which compounds could...
BACKGROUND
Pork lard (PL) is traditionally used as an anti-inflammatory agent. We propose to demonstrate the anti-inflammatory properties of PL, and elucidate which compounds could be responsible for the anti-inflammatory effects.
METHODS
The anti-inflammatory effects of PL were tested in a rat model of zymosan-induced hind paw inflammation. Further, the hydroalcoholic extract from PL was obtained, the composition analyzed, and the anti-inflammatory activity of the extracts and isolated components assayed using immune cells stimulated with lipopolysaccharide (LPS).
RESULTS
Applying the ointment on the inflamed rat feet reduced the foot diameter, foot weight, and activities of antioxidant enzymes and inflammatory markers of circulating neutrophils. The main components of the hydroalcoholic extract were 5-dodecanolide, oleamide, hexadecanoic acid, 9-octadecenoic acid, hexadecanamide, and resolvin D1.
CONCLUSIONS
PL reduces the immune response in an animal model stimulated with zymosan. Hydroalcoholic PL extract and its components (5-Dodecanolide, Oleamide, and Resolvin D1) exerted an anti-inflammatory effect on LPS-stimulated neutrophils and peripheral mononuclear cells reducing the capability to produce TNFα, as well as the activities of antioxidant and pro-inflammatory enzymes. These effects are attributable to 5-dodecanolide, although the effects of this compound alone do not reach the magnitude of the anti-inflammatory effects observed by the complete hydroalcoholic extract.
Topics: Animals; Male; Rats; Anti-Inflammatory Agents; Dietary Fats; Disease Models, Animal; Fatty Acids, Monounsaturated; Inflammation; Pork Meat; Rats, Sprague-Dawley; Swine
PubMed: 34885945
DOI: 10.3390/molecules26237363 -
FEBS Letters Jan 2022Global transcriptional regulator downstream RpfR (GtrR) is a key downstream regulator for quorum-sensing signaling molecule cis-2-dodecenoic acid (BDSF). As a bacterial...
Global transcriptional regulator downstream RpfR (GtrR) is a key downstream regulator for quorum-sensing signaling molecule cis-2-dodecenoic acid (BDSF). As a bacterial enhancer-binding protein (bEBP), GtrR is composed of an N-terminal receiver domain, a central ATPases associated with diverse cellular activities (AAA+) ATPase σ -interaction domain, and a C-terminal helix-turn-helix DNA-binding domain. In this work, we solved its AAA+ ATPase domain in both apo and GTP-bound forms. The structure revealed how GtrR specifically recognizes GTP. In addition, we also revealed that GtrR has moderate GTPase activity in vitro in the absence of its activation signal. Finally, we found the residues K170, D236, R311, and R357 in GtrR that are crucial to its biological function, any single mutation leading to completely abolishing GtrR activity.
Topics: Burkholderia cenocepacia
PubMed: 34837384
DOI: 10.1002/1873-3468.14244 -
Journal of Chemical Ecology Dec 2021Synthetic pheromones have been used for pest control over several decades. The conventional synthesis of di-unsaturated pheromone compounds is usually complex and...
Synthetic pheromones have been used for pest control over several decades. The conventional synthesis of di-unsaturated pheromone compounds is usually complex and costly. Camelina (Camelina sativa) has emerged as an ideal, non-food biotech oilseed platform for production of oils with modified fatty acid compositions. We used Camelina as a plant factory to produce mono- and di-unsaturated C chain length moth sex pheromone precursors, (E)-9-dodecenoic acid and (E,E)-8,10-dodecadienoic acid, by introducing a fatty acyl-ACP thioesterase FatB gene UcTE from California bay laurel (Umbellularia californica) and a bifunctional ∆9 desaturase gene Cpo_CPRQ from the codling moth, Cydia pomonella. Different transgene combinations were investigated for increasing pheromone precursor yield. The most productive Camelina line was engineered with a vector that contained one copy of UcTE and the viral suppressor protein encoding P19 transgenes and three copies of Cpo_CPRQ transgene. The T generation of this line produced 9.4% of (E)-9-dodecenoic acid and 5.5% of (E,E)-8,10-dodecadienoic acid of the total fatty acids, and seeds were selected to advance top-performing lines to homozygosity. In the T generation, production levels of (E)-9-dodecenoic acid and (E,E)-8,10-dodecadienoic acid remained stable. The diene acid together with other seed fatty acids were converted into corresponding alcohols, and the bioactivity of the plant-derived codlemone was confirmed by GC-EAD and a flight tunnel assay. Trapping in orchards and home gardens confirmed significant and specific attraction of C. pomonella males to the plant-derived codlemone.
Topics: Animals; Brassicaceae; Dodecanol; Metabolic Engineering; Moths; Sex Attractants
PubMed: 34762210
DOI: 10.1007/s10886-021-01316-4 -
Molecular Plant Pathology Jan 2022The Xanthomonas group of phytopathogens communicate with a fatty acid-like cell-cell signalling molecule, cis-11-2-methyl-dodecenoic acid, also known as diffusible...
The Xanthomonas group of phytopathogens communicate with a fatty acid-like cell-cell signalling molecule, cis-11-2-methyl-dodecenoic acid, also known as diffusible signal factor (DSF). In the pathogen of rice, Xanthomonas oryzae pv. oryzae, DSF is involved in the regulation of several virulence-associated functions, including production and secretion of several cell wall hydrolysing type II secretion effectors. To understand the role of DSF in the secretion of type II effectors, we characterized DSF synthase-deficient (rpfF) and DSF-deficient, type II secretion (xpsE) double mutants. Mutant analysis by expression analysis, secretion assay, fatty acid analysis, and physiological studies indicated that rpfF mutants exhibit hypersecretion of several type II effectors due to a perturbed membrane and DSF is required for maintaining membrane integrity. The rpfF mutants exhibited significantly higher uptake of 1-N-phenylnapthylamine and ethidium bromide, and up-regulation of rpoE (σ ). Increasing the osmolarity of the medium could rescue the hypersecretion phenotype of the rpfF mutant. The rpfF mutant exhibited highly reduced virulence. We report for the first time that in X. oryzae pv. oryzae RpfF is involved in the maintenance of membrane integrity by playing a regulatory role in the fatty acid synthesis pathway.
Topics: Bacterial Proteins; Gene Expression Regulation, Bacterial; Mutation; Plant Diseases; Virulence; Xanthomonas
PubMed: 34704368
DOI: 10.1111/mpp.13148 -
Microbiology Spectrum Oct 2021Asthma is a multifactorial disorder, and microbial dysbiosis enhances lung inflammation and asthma-related symptoms. Probiotics have shown anti-inflammatory effects and... (Randomized Controlled Trial)
Randomized Controlled Trial
Asthma is a multifactorial disorder, and microbial dysbiosis enhances lung inflammation and asthma-related symptoms. Probiotics have shown anti-inflammatory effects and could regulate the gut-lung axis. Thus, a 3-month randomized, double-blind, and placebo-controlled human trial was performed to investigate the adjunctive efficacy of probiotics in managing asthma. Fifty-five asthmatic patients were randomly assigned to a probiotic group ( = 29; received Bifidobacterium lactis Probio-M8 powder and Symbicort Turbuhaler) and a placebo group ( = 26; received placebo and Symbicort Turbuhaler), and all 55 subjects provided details of their clinical history and demographic data. However, only 31 patients donated a complete set of fecal and blood samples at all three time points for further analysis. Compared with those of the placebo group, co-administering Probio-M8 with Symbicort Turbuhaler significantly decreased the fractional exhaled nitric oxide level at day 30 (= 0.049) and improved the asthma control test score at the end of the intervention (= 0.023). More importantly, the level of alveolar nitric oxide concentration decreased significantly among the probiotic receivers at day 30 (= 0.038), and the symptom relief effect was even more obvious at day 90 (= 0.001). Probiotic co-administration increased the resilience of the gut microbiome, which was reflected by only minor fluctuations in the gut microbiome diversity (> 0.05, probiotic receivers; < 0.05, placebo receivers). Additionally, the probiotic receivers showed significantly changes in some species-level genome bins (SGBs), namely, increases in potentially beneficial species Bifidobacterium animalis, Bifidobacterium longum, and sp. CAG and decreases in Parabacteroides distasonis and (< 0.05). Compared with that of the placebo group, the gut metabolic potential of probiotic receivers exhibited increased levels of predicted microbial bioactive metabolites (linoleoyl ethanolamide, adrenergic acid, erythronic acid) and serum metabolites (5-dodecenoic acid, tryptophan, sphingomyelin) during/after intervention. Collectively, our results suggested that co-administering Probio-M8 synergized with conventional therapy to alleviate diseases associated with the gut-lung axis, like asthma, possibly via activating multiple anti-inflammatory pathways. The human gut microbiota has a potential effect on the pathogenesis of asthma and is closely related to the disease phenotype. Our trial has demonstrated that co-administering Probio-M8 synergized with conventional therapy to alleviate asthma symptoms. The findings of the present study provide new insights into the pathogenesis and treatment of asthma, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.
Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bifidobacterium animalis; Budesonide, Formoterol Fumarate Drug Combination; Double-Blind Method; Dysbiosis; Female; Gastrointestinal Microbiome; Humans; Lung; Male; Middle Aged; Nitric Oxide; Placebos; Probiotics; Young Adult
PubMed: 34612663
DOI: 10.1128/Spectrum.00859-21 -
Angewandte Chemie (International Ed. in... Nov 2021CYP152 peroxygenases catalyze decarboxylation and hydroxylation of fatty acids using H O as cofactor. To understand the molecular basis for the chemo- and...
CYP152 peroxygenases catalyze decarboxylation and hydroxylation of fatty acids using H O as cofactor. To understand the molecular basis for the chemo- and regioselectivity of these unique P450 enzymes, we analyze the activities of three CYP152 peroxygenases (OleT , P450 , P450 ) towards cis- and trans-dodecenoic acids as substrate probes. The unexpected 6S-hydroxylation of the trans-isomer and 4R-hydroxylation of the cis-isomer by OleT , and molecular docking results suggest that the unprecedented selectivity is due to OleT 's preference of C2-C3 cis-configuration. In addition to the common epoxide products, undecanal is the unexpected major product of P450 and P450 regardless of the cis/trans-configuration of substrates. The combined H O tracing experiments, MD simulations, and QM/MM calculations unravel an unusual mechanism for Compound I-mediated aldehyde formation in which the active site water derived from H O activation is involved in the generation of a four-membered ring lactone intermediate. These findings provide new insights into the unusual mechanisms of CYP152 peroxygenases.
Topics: Bacillus subtilis; Cytochrome P-450 Enzyme System; Fatty Acids, Unsaturated; Hydrogen Peroxide; Hydroxylation; Mixed Function Oxygenases; Molecular Dynamics Simulation; Peroxidases; Quantum Theory; Sphingomonas; Staphylococcaceae; Stereoisomerism; Substrate Specificity
PubMed: 34523786
DOI: 10.1002/anie.202111163 -
Scientific Reports Aug 2021Bioleaching of metal sulfide ores involves acidophilic microbes that catalyze the chemical dissolution of the metal sulfide bond that is enhanced by attached and...
Bioleaching of metal sulfide ores involves acidophilic microbes that catalyze the chemical dissolution of the metal sulfide bond that is enhanced by attached and planktonic cell mediated oxidation of iron(II)-ions and inorganic sulfur compounds. Leptospirillum spp. often predominate in sulfide mineral-containing environments, including bioheaps for copper recovery from chalcopyrite, as they are effective primary mineral colonizers and oxidize iron(II)-ions efficiently. In this study, we demonstrated a functional diffusible signal factor interspecies quorum sensing signaling mechanism in Leptospirillum ferriphilum and Leptospirillum ferrooxidans that produces (Z)-11-methyl-2-dodecenoic acid when grown with pyrite as energy source. In addition, pure diffusible signal factor and extracts from supernatants of pyrite grown Leptospirillum spp. inhibited biological iron oxidation in various species, and that pyrite grown Leptospirillum cells were less affected than iron grown cells to self inhibition. Finally, transcriptional analyses for the inhibition of iron-grown L. ferriphilum cells due to diffusible signal factor was compared with the response to exposure of cells to N- acyl-homoserine-lactone type quorum sensing signal compounds. The data suggested that Leptospirillum spp. diffusible signal factor production is a strategy for niche protection and defense against other microbes and it is proposed that this may be exploited to inhibit unwanted acidophile species.
PubMed: 34381075
DOI: 10.1038/s41598-021-95324-9 -
Biomaterials Science May 2021Drug-resistant pathogens are less sensitive to traditional antibiotics in many stubborn infections. It is imminently desirable to have an effective alternative...
Drug-resistant pathogens are less sensitive to traditional antibiotics in many stubborn infections. It is imminently desirable to have an effective alternative therapeutic agent for combating drug-resistant pathogen infections. Herein, a photo-triggered multifunctional nanoplatform (TMOB/FLU@PCM NPs) with efflux pump and heat shock protein expression reversal activity is developed for the highly effective eradication of drug-resistant fungi. Upon 808 nm laser excitation, the hyperthermia originating from a BODIPY derivative (TMOB) can not only melt the phase-change material (PCM) vehicle consisting of hexadecanol and cis-2-dodecenoic acid (BDSF) to on-demand release the quorum sensing molecule BDSF and the antifungal drug fluconazole (FLU), but can also destroy the integrity of the C. albicans cell membrane. Thanks to the release of BDSF from TMOB/FLU@PCM NPs, the expression of drug efflux pumps (MDR1, CDR2, CDR4) and thermotolerant proteins (HSP12, HSP21, HSP60, HSP90) is inhibited, which further boosts the therapeutic effect of chemo/photothermal therapy. Moreover, the hyphal and biofilm formation of C. albicans can be blocked by TMOB/FLU@PCM NPs under 808 nm laser irradiation. In vitro and in vivo results indicate that TMOB/FLU@PCM NPs with good biosafety can efficiently eliminate clinical azole-resistant C. albicans. Thus, TMOB/FLU@PCM NPs exhibits a promising future in the treatment of azole-resistant C. albicans infection.
Topics: Antifungal Agents; Candida albicans; Fluconazole; Heat-Shock Proteins
PubMed: 33861264
DOI: 10.1039/d1bm00457c