scholarly journals Antimicrobial Peptide Dendrimers and Quorum-Sensing Inhibitors in Formulating Next-Generation Anti-Infection Cell Therapy Dressings for Burns

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3839
Author(s):  
Paris Jafari ◽  
Alexandre Luscher ◽  
Thissa Siriwardena ◽  
Murielle Michetti ◽  
Yok-Ai Que ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Cell Therapy ◽  
Antimicrobial Peptide ◽  
Progenitor Cells ◽  
Pathogenic Bacteria ◽  
Bactericidal Effect ◽  
Burn Wound ◽  
Peptide Dendrimers ◽  
Cause Of Failure ◽  
A Cell

Multidrug resistance infections are the main cause of failure in the pro-regenerative cell-mediated therapy of burn wounds. The collagen-based matrices for delivery of cells could be potential substrates to support bacterial growth and subsequent lysis of the collagen leading to a cell therapy loss. In this article, we report the development of a new generation of cell therapy formulations with the capacity to resist infections through the bactericidal effect of antimicrobial peptide dendrimers and the anti-virulence effect of anti-quorum sensing MvfR (PqsR) system compounds, which are incorporated into their formulation. Anti-quorum sensing compounds limit the pathogenicity and antibiotic tolerance of pathogenic bacteria involved in the burn wound infections, by inhibiting their virulence pathways. For the first time, we report a biological cell therapy dressing incorporating live progenitor cells, antimicrobial peptide dendrimers, and anti-MvfR compounds, which exhibit bactericidal and anti-virulence properties without compromising the viability of the progenitor cells.

scholarly journals ThefsrQuorum-Sensing System and Cognate Gelatinase Orchestrate the Expression and Processing of Proprotein EF_1097 into the Mature Antimicrobial Peptide Enterocin O16

2015 ◽  
Vol 197 (13) ◽  
pp. 2112-2121 ◽  
Author(s):  
Halil Dundar ◽  
Dag A. Brede ◽  
Sabina Leanti La Rosa ◽  
Ahmed Osama El-Gendy ◽  
Dzung B. Diep ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Quorum Sensing ◽  
Antimicrobial Peptide ◽  
Bioinformatic Analysis ◽  
Dependent Manner ◽  
Content Type ◽  
Sensing System ◽  
Quorum Sensing System ◽  
Inhibitory Spectrum ◽  
A Cell

ABSTRACTA novel antimicrobial peptide designated enterocin O16 was purified fromEnterococcus faecalis. Mass spectrometry showed a monoisotopic mass of 7,231 Da, and N-terminal Edman degradation identified a 29-amino-acid sequence corresponding to residues 90 to 119 of the EF_1097 protein. Bioinformatic analysis showed that enterocin O16 is composed of the 68 most C-terminal residues of the EF_1097 protein. Introduction of an in-frame isogenic deletion in theef1097gene abolished the production of enterocin O16. Enterocin O16 has a narrow inhibitory spectrum, as it inhibits mostly lactobacilli. Apparently,E. faecalisis intrinsically resistant to the antimicrobial peptide, as no immunity connected to the production of enterocin O16 could be identified.ef1097has previously been identified as one of three loci regulated by thefsrquorum-sensing system. The introduction of a nonsense mutation intofsrBconsistently impaired enterocin O16 production, but externally added gelatinase biosynthesis-activating pheromone restored the antimicrobial activity. Functional genetic analysis showed that the EF_1097 proprotein is processed extracellularly into enterocin O16 by the metalloprotease GelE. Thus, it is evident that thefsrquorum-sensing system constitutes the regulatory unit that controls the expression of the EF_1097 precursor protein and the protease GelE and that the latter is required for the formation of enterocin O16. On the basis of these results, this study identified antibacterial antagonism as a novel aspect related to the function offsrand provides a rationale for whyef1097is part of thefsrregulon.IMPORTANCEThefsrquorum-sensing system modulates important physiological functions inE. faecalisvia the activity of GelE. The present study presents a new facet offsrsignaling. The system controls the expression of three primary target operons (fsrABCD,gelE-sprE, andef1097-ef1097b). We demonstrate that the concerted expression of these operons constitutes the elements necessary for the production of a bacteriocin-type peptide and that antimicrobial antagonism is an intrinsic function offsr. The bacteriocin enterocin O16 consists of the 68 most C-terminal residues of the EF_1097 secreted proprotein. The GelE protease processes the EF_1097 proprotein into enterocin O16. In this manner,fsrsignaling enablesE. faecalispopulations to express antimicrobial activity in a cell density-dependent manner.

scholarly journals Perspectives of cell therapy for myocardial infarction and heart failure based on cardiosphere cells

2020 ◽  
Vol 92 (4) ◽  
pp. 111-120 ◽  
Author(s):  
K. V. Dergilev ◽  
Iu. D. Vasilets ◽  
Z. I. Tsokolaeva ◽  
E. S. Zubkova ◽  
E. V. Parfenova
Keyword(s):  
Cell Therapy ◽  
Progenitor Cells ◽  
Heart Diseases ◽  
Three Dimensional ◽  
Matrix Proteins ◽  
Multicellular Spheroids ◽  
Low Degree ◽  
A Cell ◽  
Therapeutic Properties ◽  
Preclinical And Clinical Studies

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. In recent years, researchers are attracted to the use of cell therapy based on stem cell and progenitor cells, which has been a promising strategy for cardiac repair after injury. However, conducted research using intracoronary or intramyocardial transplantation of various types of stem/progenitor cells as a cell suspension showed modest efficiency. This is due to the low degree of integration and cell survival after transplantation. To overcome these limitations, the concept of the use of multicellular spheroids modeling the natural microenvironment of cells has been proposed, which allows maintaining their viability and therapeutic properties. It is of great interest to use so-called cardial spheroids (cardiospheres) spontaneously forming three-dimensional structures under low-adhesive conditions, consisting of a heterogeneous population of myocardial progenitor cells and extracellular matrix proteins. This review presents data on methods for creating cardiospheres, directed regulation of their properties and reparative potential, as well as the results of preclinical and clinical studies on their use for the treatment of heart diseases.

Breakthrough Regenerative Cardiopoietic Stem Cells and Related Technologies in the Field of Cardiovascular Medicine – From Bench to Bedside

2012 ◽  
Vol 7 (1) ◽  
pp. 14
Author(s):  
Christian Homsy ◽  
Keyword(s):  
Stem Cells ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Cardiac Disease ◽  
Cardiac Tissue ◽  
Cardiac Repair ◽  
Cardiac Diseases ◽  
Cardiac Progenitor Cells ◽  
Biotechnology Company ◽  
Cardiovascular Medicine

The scale of cardiac diseases, and in particular heart failure and acute myocardial infarction, emphasises the need for radically new approaches, such as cell therapy, to address the underlying cause of the disease, the loss of functional myocardium. Stem cell-based therapies, whether through transplanted cells or directing innate repair, may provide regenerative approaches to cardiac diseases by halting, or even reversing, the events responsible for progression of organ failure. Cardio3 BioSciences, a leading Belgian biotechnology company focused on the discovery and development of regenerative and protective therapies for the treatment of cardiac disease, was founded in this context in 2004. The company is developing a highly innovative cell therapy approach based on a platform designed to reprogramme the patient’s own stem cells into cardiac progenitor cells. The underlying rationale behind this approach is that, in order to reconstruct cardiac tissue, stem cells need to be specific to cardiac tissue. The key is therefore to provide cardiac-specific progenitor cells to the failing heart to induce cardiac repair.

scholarly journals Assessing the Molecular Targets and Mode of Action of Furanone C-30 on Pseudomonas aeruginosa Quorum Sensing

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1620
Author(s):  
Victor Markus ◽  
Karina Golberg ◽  
Kerem Teralı ◽  
Nazmi Ozer ◽  
Esti Kramarsky-Winter ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Conformational Changes ◽  
Mode Of Action ◽  
Pathogenic Bacteria ◽  
Molecular Targets ◽  
Resistant Bacteria ◽  
Public Healthcare ◽  
C 30

Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein’s productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date.

Effects of hypoxia on osteogenic differentiation of mesenchymal stromal cells used as a cell therapy for avascular necrosis of the femoral head

Cytotherapy ◽  
2016 ◽  
Vol 18 (9) ◽  
pp. 1087-1099 ◽  
Author(s):  
Gabriela Ciapetti ◽  
Donatella Granchi ◽  
Caterina Fotia ◽  
Lucia Savarino ◽  
Dante Dallari ◽  
...  
Keyword(s):  
Femoral Head ◽  
Cell Therapy ◽  
Osteogenic Differentiation ◽  
Avascular Necrosis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
A Cell

scholarly journals PapRIV, a BV-2 microglial cell activating quorum sensing peptide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yorick Janssens ◽  
Nathan Debunne ◽  
Anton De Spiegeleer ◽  
Evelien Wynendaele ◽  
Marta Planas ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Cell Model ◽  
Dependent Manner ◽  
Communication Signals ◽  
Gram Positive Bacteria ◽  
A Cell ◽  
Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

scholarly journals Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Orit Malka ◽  
Dorin Kalson ◽  
Karin Yaniv ◽  
Reut Shafir ◽  
Manikandan Rajendran ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Gut Microbiome ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
Human Microbiome ◽  
Cell Communication ◽  
Probiotic Yeast ◽  
Gut Pathogen ◽  
Cell Cell

Abstract Background Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome. Results The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite—tryptophol acetate—which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways. Conclusions This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule—tryptophol acetate—was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases.

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