-
Journal of Medicinal Chemistry Oct 2022In view of the worldwide antimicrobial resistance (AMR) threat, new bacterial targets and anti-infective agents are needed. Since important roles in bacterial...
In view of the worldwide antimicrobial resistance (AMR) threat, new bacterial targets and anti-infective agents are needed. Since important roles in bacterial pathogenesis have been demonstrated for the collagenase H and G (ColH and ColG) from , collagenase Q1 and A (ColQ1 and ColA) from represent attractive antivirulence targets. Furthermore, repurposing FDA-approved drugs may assist to tackle the AMR crisis and was addressed in this work. Here, we report on the discovery of two potent and chemically stable bacterial collagenase inhibitors: synthesized and FDA-approved diphosphonates and hydroxamates. Both classes showed high activity against the clostridial and bacillary collagenases. The potent diphosphonates reduced -mediated detachment and death of cells and larvae. The hydroxamates were also tested in a similar manner; they did not have an effect in infection models. This might be due to their fast binding kinetics to bacterial collagenases.
Topics: Clostridium histolyticum; Collagenases; Diphosphonates; Matrix Metalloproteinase Inhibitors; Microbial Collagenase
PubMed: 36154055
DOI: 10.1021/acs.jmedchem.2c00785 -
Brazilian Journal of Microbiology :... 2017Specific proteases capable of degrading native triple helical or denatured collagen have been required for many years and have a large spectrum of applications. There... (Meta-Analysis)
Meta-Analysis Review
Specific proteases capable of degrading native triple helical or denatured collagen have been required for many years and have a large spectrum of applications. There are few complete reports that fully uncover production, characterization and purification of fungi collagenases. In this review, authors searched through four scientific on line data bases using the following keywords (collagenolytic OR collagenase) AND (fungi OR fungus OR fungal) AND (production OR synthesis OR synthesize) AND (characterization). Scientific criteria were adopted in this review to classify found articles by score (from 0 to 10). After exclusion criteria, 21 articles were selected. None obtained the maximum of 10 points defined by the methodology, which indicates a deficiency in studies dealing simultaneously with production, characterization and purification of collagenase by fungi. Among microorganisms studied the non-pathogenic fungi Penicillium aurantiogriseum and Rhizoctonia solani stood out in volumetric and specific collagenase activity. The only article found that made sequencing of a true collagenase showed 100% homology with several metalloproteinases fungi. A clear gap in literature about collagenase production by fungi was verified, which prevents further development in the area and increases the need for further studies, particularly full characterization of fungal collagenases with high specificity to collagen.
Topics: Collagen; Collagenases; Culture Media; Enzyme Activation; Fungi; Proteolysis; Substrate Specificity
PubMed: 27756540
DOI: 10.1016/j.bjm.2016.08.001 -
International Wound Journal Dec 2017Enzymatic debridement with collagenase is a technique that is commonly used in clinical practice. This systematic review examines the effect of collagenase on all kinds... (Meta-Analysis)
Meta-Analysis Review
Enzymatic debridement with collagenase is a technique that is commonly used in clinical practice. This systematic review examines the effect of collagenase on all kinds of wounds, compared to an alternative therapy, on wound healing, wound bed characteristics, cost-effectiveness and the occurrence of adverse events. We conducted a systematic literature search on available literature in Cochrane databases, MEDLINE, EMBASE and CINAHL. Two investigators independently assessed the titles and abstracts of all randomised controlled trials obtained involving collagenase of all kinds of wounds based on inclusion criteria. Of the 1411 citations retrieved, 22 studies reported outcomes with the use of collagenase either for wound healing or wound debridement. Results support the use of collagenase for enzymatic debridement in pressure ulcers, diabetic foot ulcers and in conjunction with topical antibiotics for burns. However, studies presented a high risk of bias. Risk ratio of developing an adverse event related to collagenase versus the alternative treatment was statistically significant (for 10 studies, RR: 1·79, 95% CI 1·24-2·59, I =0%, P = 0·002). There is very limited data on the effect of collagenase as an enzymatic debridement technique on wounds. More independant research and adequate reporting of adverse events are warranted.
Topics: Burns; Collagenases; Debridement; Humans; Skin Ulcer; Wound Healing
PubMed: 28440050
DOI: 10.1111/iwj.12760 -
Journal of Oleo Science 2023The anti-cancer activities of the compounds were evaluated against KYSE-150, KYSE-30, and KYSE-270 cell lines and also on investigated esophageal line HET 1 A as a...
The anti-cancer activities of the compounds were evaluated against KYSE-150, KYSE-30, and KYSE-270 cell lines and also on investigated esophageal line HET 1 A as a standard. Modified inhibitory impact on enzymes of collagenase and elastase were used Thring and Moon methods, respectively. Among both compounds, both of them recorded impact on cancer cells being neutral against the control, both had IC50 lower than 100 µM and acted as a potential anticancer drug. The chemical activities of Skullcapflavone I and Skullcapflavone II against elastase and collagenase were investigated utilizing the molecular modeling study. IC50 values of Skullcapflavone I and Skullcapflavone II on collagenase enzyme were obtained 106.74 and 92.04 µM and for elastase enzyme were 186.70 and 123.52 µM, respectively. Anticancer effects of these compounds on KYSE 150, KYSE 30, and KYSE 270 esophageal cancer cell lines studied in this work. For Skullcapflavone I, IC50 values for these cell lines were obtained 14.25, 19.03, 25.10 µM, respectively. Also, for Skullcapflavone II were recorded 20.42, 34.17, 22.40 µM, respectively. The chemical activities of Skullcapflavone I and Skullcapflavone II against some of the expressed surface receptor proteins (CD44, EGFR, and PPARγ) in the mentioned cell lines were assessed using the molecular docking calculations. The calculations showed the possible interactions and their characteristics at an atomic level.
Topics: Antineoplastic Agents; Cell Line; Cell Proliferation; Drug Screening Assays, Antitumor; Molecular Docking Simulation; Molecular Structure; Pancreatic Elastase; Structure-Activity Relationship; Collagenases; Peptide Hydrolases
PubMed: 37121681
DOI: 10.5650/jos.ess22337 -
Molecules (Basel, Switzerland) Feb 2023Aging is a complex physiological process that can be accelerated by chemical (high blood glucose levels) or physical (solar exposure) factors. It is accompanied by the...
Aging is a complex physiological process that can be accelerated by chemical (high blood glucose levels) or physical (solar exposure) factors. It is accompanied by the accumulation of altered molecules in the human body. The accumulation of oxidatively modified and glycated proteins is associated with inflammation and the progression of chronic diseases (aging). The use of antiglycating agents is one of the recent approaches in the preventive strategy of aging and natural compounds seem to be promising candidates. Our study focused on the anti-aging effect of the flavonoid hesperetin, its glycoside hesperidin and its carbohydrate moieties rutinose and rhamnose on young and physiologically aged normal human dermal fibroblasts (NHDFs). The anti-aging activity of the test compounds was evaluated by measuring matrix metalloproteinases (MMPs) and inflammatory interleukins by ELISA. The modulation of elastase, hyaluronidase, and collagenase activity by the tested substances was evaluated spectrophotometrically by tube tests. Rutinose and rhamnose inhibited the activity of pure elastase, hyaluronidase, and collagenase. Hesperidin and hesperetin inhibited elastase and hyaluronidase activity. In skin aging models, MMP-1 and MMP-2 levels were reduced after application of all tested substances. Collagen I production was increased after the application of rhamnose and rutinose.
Topics: Humans; Collagenases; Hesperidin; Hyaluronoglucosaminidase; Pancreatic Elastase; Rhamnose; Skin Aging
PubMed: 36838716
DOI: 10.3390/molecules28041728 -
Clinical Oral Investigations Apr 2021Resin-based composites may leach monomers such as triethylene-glycol dimethacrylate (TEGDMA), which could contribute to intrapulpal inflammation. The aim of this...
OBJECTIVES
Resin-based composites may leach monomers such as triethylene-glycol dimethacrylate (TEGDMA), which could contribute to intrapulpal inflammation. The aim of this investigation was to examine whether various concentrations of TEGDMA are able to influence dentally relevant Matrix metalloproteinase (MMP)-2, MMP-8, and MMP-9 production, total collagenase/gelatinase activity in pulp cells, and suggest possible signaling mechanisms.
MATERIALS AND METHODS
Pulp cells were cultured, followed by a 1-day exposure to sublethal TEGDMA concentrations (0.1, 0.2, and 0.75 mM). Total MMP activity was measured by an EnzCheck total collagenase/gelatinase assay, while the production of specific MMPs and the relative changes of phosphorylated, i.e., activated signaling protein levels of extracellular signal-regulated kinase (ERK)1/2, p38, c-Jun N-terminal kinase (JNK) were identified by western blot. Immunocytochemistry image data was also plotted and analyzed to see whether TEGDMA could possibly alter MMP production.
RESULTS
An increase in activated MMP-2, MMP-8, and MMP-9 production as well as total collagenase activity was seen after a 24-h exposure to the abovementioned TEGDMA concentrations. Increase was most substantial at 0.1 (P = 0.002) and 0.2 mM (P = 0.0381). Concurrent p-ERK, p-p38, and p-JNK elevations were also detected.
CONCLUSIONS
Results suggest that monomers such as TEGDMA, leached from resin-based restorative materials, activate and induce the production of dentally relevant MMPs in pulp cells. Activation of ERK1/2, p38, or JNK and MMP increase may play a role in and/or can be part of a broader stress response. Clinical relevance Induction of MMP production and activity may further be components in the mechanisms of intrapulpal monomer toxicity.
Topics: Cells, Cultured; Collagenases; Matrix Metalloproteinase 2; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Polyethylene Glycols; Polymethacrylic Acids
PubMed: 32845470
DOI: 10.1007/s00784-020-03545-5 -
Cell Transplantation Oct 2017Animal-free (AF) SERVA Collagenase AF-1 and Neutral Protease (NP) AF GMP Grade have recently become available for human islet isolation. This report describes the...
Animal-free (AF) SERVA Collagenase AF-1 and Neutral Protease (NP) AF GMP Grade have recently become available for human islet isolation. This report describes the initial experiences of 3 different islet transplant centers. Thirty-four human pancreases were digested using 1 vial of the 6 different lots of Collagenase AF-1 (2,000-2,583 PZ-U/vial) supplemented with 4 different lots of NP AF in a range of 50 to 160 DMC-U per pancreas. Isolation, culture, and quality assessment were performed using standard techniques as previously described. All data are presented as mean ± standard error of the mean (SEM). Variability of pancreas weight was associated with a wide range of collagenase and NP activities, ranging from 12.7 to 46.6 PZ-U/g (26.0 ± 1.5 PZ-U/g) and 0.4 to 3.0 DMC-U/g (1.5 ± 0.1 DMC-U/g), respectively. Postpurification islet yield was 296,494 ± 33,620 islet equivalents (IEQ) equivalent to 3,274 ± 450 IEQ/g with a purity of 55.9% ± 3.2%. Quality assessment performed after 2 to 4 d of culture demonstrated a viability of 88.1% ± 1.5% and a stimulation index of 3.7 ± 0.7. Eighteen of the 34 preparations were transplanted into type 1 diabetic patients equivalent to a transplantation rate of 52.9%. Six preparations, which were infused into patients as first transplant, could be analyzed and increased the fasting C-peptide level from 0.11 ± 0.08 pretransplant to 1.23 ± 0.24 and 2.27 ± 0.31 ng/mL 3 and 6 mo posttransplant ( P < 0.05), respectively. Insulin requirements were simultaneously reduced at the same time from 39.2 ± 3.8 IU/d before transplantation to 10.8 ± 4.1 and 4.0 ± 2.3 IU/d, after 3 and 6 mo posttransplant ( P < 0.05), respectively. This study demonstrates the efficiency of AF SERVA Collagenase AF-1 and NP AF for clinical islet isolation and transplantation. The new plant-based production process makes these products a safe new option for the islet field.
Topics: Cell Separation; Collagenases; Female; Humans; Islets of Langerhans Transplantation; Male; Middle Aged
PubMed: 29251107
DOI: 10.1177/0963689717731574 -
Medical Principles and Practice :... 2020The objective of this study was to evaluate the efficacy of subacromial injections of collagenase and corticosteroid in rats with experimentally induced adhesive... (Comparative Study)
Comparative Study
BACKGROUND
The objective of this study was to evaluate the efficacy of subacromial injections of collagenase and corticosteroid in rats with experimentally induced adhesive capsulitis.
METHOD
Thirty adult Wistar albino male rats were distributed into 3 groups of 10 rats each after stabilization of their shoulders for 3 weeks: the first group received a single dose of 0.002 mg (0.25 mL) subacromial collagenase; the second group received a single dose of 1.60 mg (0.25 mL) subacromial steroid, and the third group received a single dose of 0.25 mL subacromial saline solution. One week later, we investigated shoulder range of motions, collagen content of the shoulder, and joint cartilage structure.
RESULTS
There was no statistically significant difference in the cartilage damage between the groups (p > 0.05). Fibrosis measurements were significantly lower in the collagenase group than in the steroid and saline groups. There was no significant difference in fibrosis between the steroid and saline groups (p > 0.05). Abduction measurements were significantly higher in the collagenase group than in the steroid and saline groups (p < 0.001). No significant difference in the abduction measurements was observed between the saline and steroid groups (p > 0.05).
CONCLUSION
We observed that subacromial injections of collagenase Clostridium histolyticum effectively treated adhesive capsulitis. The results suggest that this treatment could be considered for use in patients with an intact rotator cuff.
Topics: Animals; Bursitis; Collagenases; Male; Range of Motion, Articular; Rats; Rats, Wistar
PubMed: 31480049
DOI: 10.1159/000503086 -
Frontiers in Cellular and Infection... 2021Extracellular matrix (ECM) degrading enzymes produced by may play an important role during the initial phases of avian necrotic enteritis by facilitating toxin entry...
Extracellular matrix (ECM) degrading enzymes produced by may play an important role during the initial phases of avian necrotic enteritis by facilitating toxin entry in the intestinal mucosa and destruction of the tissue. is known to produce several ECM-degrading proteases, such as kappa toxin, an extracellular collagenase that is encoded by the gene. In this study, the gene sequence of a collection of 48 strains, including pathogenic (i.e. toxinotype G) and commensal (i.e. toxinotype A) chicken derived strains and strains originating from other host species, was analyzed. Although the gene showed a high level of conservation (>96% nucleotide sequence identity), several gene variants carrying different nonsense mutations in the gene were identified, leading to the definition of four truncated collagenase variant types (I-IV). Collagenase variant types I, III and IV have a (nearly) complete collagenase unit but lack parts of the C-terminal recruitment domains, whereas collagenase variant types II misses the N-terminal part of collagenase unit. Gene fragments encoding a truncated collagenase were mainly linked with necrotic enteritis associated type G strains with collagenase variant types I and II being the most prevalent types. Gelatin zymography revealed that both recombinant full-length and variant type I collagenase have active auto-cleavage products. Moreover, both recombinant fragments were capable of degrading type I as well as type IV collagen, although variant type I collagenase showed a higher relative activity against collagen type IV as compared to full-length collagenase. Consequently, these smaller truncated collagenases might be able to break down collagen type IV in the epithelial basement membrane of the intestinal villi and so contribute to the initiation of the pathological process leading to necrotic enteritis.
Topics: Animals; Chickens; Clostridium Infections; Clostridium perfringens; Collagenases; Enteritis; Poultry Diseases
PubMed: 33996628
DOI: 10.3389/fcimb.2021.645248 -
Applied and Environmental Microbiology Sep 2015Bacterial collagenolytic proteases are important because of their essential role in global collagen degradation and because of their virulence in some human bacterial... (Review)
Review
Bacterial collagenolytic proteases are important because of their essential role in global collagen degradation and because of their virulence in some human bacterial infections. Bacterial collagenolytic proteases include some metalloproteases of the M9 family from Clostridium or Vibrio strains, some serine proteases distributed in the S1, S8, and S53 families, and members of the U32 family. In recent years, there has been remarkable progress in discovering new bacterial collagenolytic proteases and in investigating the collagen-degrading mechanisms of bacterial collagenolytic proteases. This review provides comprehensive insight into bacterial collagenolytic proteases, especially focusing on the structures and collagen-degrading mechanisms of representative bacterial collagenolytic proteases in each family. The roles of bacterial collagenolytic proteases in human diseases and global nitrogen cycling, together with the biotechnological and medical applications for these proteases, are also briefly discussed.
Topics: Bacteria; Collagen; Collagenases; Genetic Variation; Humans; Models, Chemical; Models, Molecular; Protein Conformation; Proteolysis
PubMed: 26150451
DOI: 10.1128/AEM.00883-15