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Applied and Environmental Microbiology Oct 2023Outer membrane vesicle (OMV)-delivered quinolone signal (PQS) plays a critical role in cell-cell communication in . However, the functions and mechanisms of...
Outer membrane vesicle (OMV)-delivered quinolone signal (PQS) plays a critical role in cell-cell communication in . However, the functions and mechanisms of membrane-enclosed PQS in interspecies communication in microbial communities are not clear. Here, we demonstrate that PQS delivered by both OMVs from and liposome reduces the competitiveness of , which usually shares the same niche in the lungs of cystic fibrosis patients, by interfering with quorum sensing (QS) in through the LysR-type regulator ShvR. Intriguingly, we found that ShvR regulates the production of the QS signals cis-2-dodecenoic acid (BDSF) and N-acyl homoserine lactone (AHL) by directly binding to the promoters of signal synthase-encoding genes. Perception of PQS influences the regulatory activity of ShvR and thus ultimately reduces QS signal production and virulence in . Our findings provide insights into the interspecies communication mediated by the membrane-enclosed QS signal among bacterial species residing in the same microbial community.IMPORTANCEQuorum sensing (QS) is a ubiquitous cell-to-cell communication mechanism. Previous studies showed that mainly employs cis-2-dodecenoic acid (BDSF) and N-acyl homoserine lactone (AHL) QS systems to regulate biological functions and virulence. Here, we demonstrate that quinolone signal (PQS) delivered by outer membrane vesicles from or liposome attenuates virulence by targeting the LysR-type regulator ShvR, which regulates the production of the QS signals BDSF and AHL in a. Our results not only suggest the important roles of membrane-enclosed PQS in interspecies and interkingdom communications but also provide a new perspective on the use of functional nanocarriers loaded with QS inhibitors for treating pathogen infections.
Topics: Humans; Quorum Sensing; Virulence; Acyl-Butyrolactones; Liposomes; Bacterial Proteins; Burkholderia cenocepacia; Pseudomonas aeruginosa; Gene Expression Regulation, Bacterial
PubMed: 37796010
DOI: 10.1128/aem.01184-23 -
Molecular Plant-microbe Interactions :... Jan 2024Numerous bacterial species employ diffusible signal factor (DSF)-based quorum sensing (QS) as a widely conserved cell-cell signaling communication system to collectively... (Review)
Review
Numerous bacterial species employ diffusible signal factor (DSF)-based quorum sensing (QS) as a widely conserved cell-cell signaling communication system to collectively regulate various behaviors crucial for responding to environmental changes. -11-Methyl-dodecenoic acid, known as DSF, was first identified as a signaling molecule in pv. . Subsequently, many structurally related molecules have been identified in different bacterial species. This review aims to provide an overview of current understanding regarding the biosynthesis and regulatory role of DSF signals in both pathogenic bacteria and a biocontrol bacterium. Recent studies have revealed that the DSF-based QS system regulates antimicrobial factor production in a cyclic dimeric GMP-independent manner in the biocontrol bacterium . Additionally, the DSF family signals have been found to be involved in suppressing plant innate immunity. The discovery of these diverse signaling mechanisms holds significant promise for developing novel strategies to combat stubborn plant pathogens. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Topics: Quorum Sensing; Xanthomonas campestris; Signal Transduction; Cyclic GMP; Bacterial Proteins
PubMed: 37880815
DOI: 10.1094/MPMI-05-23-0074-CR -
Cell Reports May 2024Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR controls Burkholderia...
Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR controls Burkholderia cenocepacia virulence as a cis-2-dodecenoic acid (BDSF) QS signal receptor. Here, we report that the fatty acyl-CoA ligase DsfR (BCAM2136), which efficiently catalyzes in vitro synthesis of lauryl-CoA and oleoyl-CoA from lauric acid and oleic acid, respectively, acts as a global transcriptional regulator to control B. cenocepacia virulence by sensing BDSF. We show that BDSF binds to DsfR with high affinity and enhances the binding of DsfR to the promoter DNA regions of target genes. Furthermore, we demonstrate that the homolog of DsfR in B. lata, RS02960, binds to the target gene promoter, and perception of BDSF enhances the binding activity of RS02960. Together, these results provide insights into the evolved unusual functions of DsfR that control bacterial virulence as a response regulator of QS signal.
Topics: Quorum Sensing; Burkholderia cenocepacia; Virulence; Bacterial Proteins; Coenzyme A Ligases; Gene Expression Regulation, Bacterial; Promoter Regions, Genetic; Animals; Signal Transduction; Fatty Acids, Monounsaturated; Mice; Protein Binding; Lauric Acids
PubMed: 38748879
DOI: 10.1016/j.celrep.2024.114223 -
The Journal of Infectious Diseases Mar 2024Bone infections from Staphylococcus aureus are notoriously difficult to treat and have high recurrence rates. Local antibiotic delivery systems hold the potential to...
BACKGROUND
Bone infections from Staphylococcus aureus are notoriously difficult to treat and have high recurrence rates. Local antibiotic delivery systems hold the potential to achieve high in situ antibiotic concentrations, which are otherwise challenging to achieve via systemic administration. Existing solutions have been shown to confer suboptimal drug release and distribution. Here we present and evaluate an injectable in situ-forming depot system termed CarboCell. The CarboCell technology provides sustained and tuneable release of local high-dose antibiotics.
METHODS
CarboCell formulations of levofloxacin or clindamycin with or without antimicrobial adjuvants cis-2-decenoic acid or cis-11-methyl-2-dodecenoic acid were tested in experimental rodent and porcine implant-associated osteomyelitis models. In the porcine models, debridement and treatment with CarboCell-formulated antibiotics was carried out without systemic antibiotic administration. The bacterial burden was determined by quantitative bacteriology.
RESULTS
CarboCell formulations eliminated S. aureus in infected implant rat models. In the translational implant-associated pig model, surgical debridement, and injection of clindamycin-releasing CarboCell formulations resulted in pathogen-free bone tissues and implants in 9/12, and full eradication in 5/12 pigs.
CONCLUSIONS
Sustained release of antimicrobial agents mediated by the CarboCell technology demonstrated promising therapeutic efficacy in challenging translational models and may be beneficial in combination with the current standard of care.
PubMed: 38537273
DOI: 10.1093/infdis/jiae139 -
Reproductive Toxicology (Elmsford, N.Y.) Apr 2024Apilarnil, a bee-derived product originating from drone larvae, offers a range of advantageous properties for both humans and animals. It functions as an antioxidant,...
Apilarnil, a bee-derived product originating from drone larvae, offers a range of advantageous properties for both humans and animals. It functions as an antioxidant, provides neuroprotection, boosts fertility, and has antiviral capabilities. Additionally, it is a provider of androgenic hormones. These beneficial functions are supported by its chemical composition, which comprises mineral salts, vitamins, carbs, lipids, hormones, and amino acids. The current study aimed to evaluate the ameliorative effect of apilarnil against Bisphenol A (BPA)-induced testicular toxicity in male adult rats. Forty-eight Wistar albino rats were randomly classified into six groups. The first, second, and third received olive oil, BPA at a dose of 50 mg/kg body weight (bwt), and apilarnil at a dose of 0.6 g/kg bwt, respectively. The fourth, fifth, and sixth groups received apilarnil with, before, or after BPA administration, respectively. Phytochemical analysis using included linear ion trap-ultra-performance liquid chromatography-tandem mass spectrometry (LTQ-UPLC-MS/MS) and global natural products social molecular networking (GNPS) revealed the presence of lysine, 10-hydroxy-(E)-2-dodecenoic acid, apigenin7-glucoside, testosterone, progesterone, and campesterol. BPA administration decreased serum level of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, glutathione (GSH) concentration, total sperm count, motility, and vitality. Additionally, BPA increased sperm abnormalities, malondialdehyde concentration (MDA), and decreased proliferating cell nuclear antigen (PCNA) expression. The treatment with apilarnil ameliorated BPA reproductive toxicity in rats which was indicated by increased serum testosterone levels, normalized serum levels of FSH and LH, and concentration of MDA and GSH activity. Moreover, apilarnil improved sperm count, motility, morphology, and PCNA expression. Apilarnil was found to enhance reproductive hormones, MDA levels, antioxidant activity, and PCNA expression.
Topics: Adult; Animals; Humans; Male; Rats; Antioxidants; Benzhydryl Compounds; Biological Products; Chromatography, Liquid; Follicle Stimulating Hormone; Glutathione; Luteinizing Hormone; Oxidative Stress; Phenols; Proliferating Cell Nuclear Antigen; Rats, Wistar; Sperm Count; Tandem Mass Spectrometry; Testis; Testosterone
PubMed: 38484946
DOI: 10.1016/j.reprotox.2024.108570