hamamelitannin and Staphylococcal-Infections

Staphylococcal spp. are notorious for causing biofilm-related device-associated infections, leading to tens of thousands of deaths per year. In this paper, we review quorum sensing inhibitors as potential therapeutics for even the most persistent infections. The animal models reviewed are subcutaneous graft, central venous catheter (CVC), ureteral stent and wound models, and a wound case study. The therapeutic approaches reviewed are the use of RNAIII inhibiting peptide (RIP) and its non-peptide analog. These have been shown to prevent or treat infections caused by any staphylococcal strain tested, including antibiotic-resistant strains like CA-MRSA USA300.

Topics: Animals; Anti-Infective Agents; Biofilms; Catheter-Related Infections; Catheters, Indwelling; Disease Models, Animal; Drug Resistance, Bacterial; Gallic Acid; Hexoses; Humans; Methicillin-Resistant Staphylococcus aureus; Prosthesis-Related Infections; Quorum Sensing; Ribosome Inactivating Proteins; Staphylococcal Infections; Staphylococcus; Stents; Surgical Wound Infection; Wound Healing

To characterise the biofilm matrix composition of a newly described Staphylococcus aureus biofilm phenotype.. This experimental study was conducted at the Faculty of Pharmacy, Helwan University, Cairo, Egypt, from January 2021 to March 2022, and comprised methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus biofilm-forming clinical isolates which were allowed to construct biofilms under two distinct culture conditions; one a commonly used condition, and the other one a novel, more biologically-relevant condition. The formed biofilms were analysed for matrix composition through treatment with proteinase,sodium meta-periodate, and streptokinase. The efficacy of Cis-2-Decenoic acid and hamamelitannin on the biologically-relevant biofilms was evaluated using biofilm viability assay based on a colorimetric assay for measuring cell metabolic activity and scanning electron microscope imaging. Data was analysed using GraphPad Prism 5.01.. Of the 58 isolates, 45(77.6%) were methicillin-resistant Staphylococcus aureus and 13(22.4%) were methicillin susceptible Staphylococcus aureus. There was significant difference in responses to streptokinase, proteinase and sodium meta-periodate (p<0.05) among the differentially-developed biofilms in methicillin-resistant Staphylococcus aureus isolates. Regarding the methicillin-susceptible Staphylococcus aureus isolates, the differentially-developed biofilms showed significantly different liabilities to streptokinase only (p<0.05). Mean biofilm inhibition for Cis-2- Decenoic acid was 54.27±27.93% and mean biofilm dispersion was 71.92±11.59% while the corresponding valuesfor hamamelitannin were 83.03±13.95% and 70.48±7.116% against the newly described methicillin-resistant Staphylococcus aureus biofilm phenotype.. Applying biologically-relevant culture conditions on staphylococci biofilms and antibiofilm drugs is recommended.

Topics: Anti-Bacterial Agents; Biofilms; Humans; Methicillin; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Peptide Hydrolases; Phenotype; Sodium; Staphylococcal Infections; Staphylococcus aureus; Streptokinase

Staphylococcus aureus is a frequent cause of biofilm-related infections. Bacterial cells within a biofilm are protected from attack by the immune system and conventional antibiotics often fail to penetrate the biofilm matrix. The discovery of hamamelitannin as a potentiator for antibiotics, recently led to the design of a more drug-like lead. In the present study, we want to gain further insight into the structure-activity relationship (S.A.R.) of the 5-position of the molecule, by preparing a library of 21 hamamelitannin analogues.

Topics: Anti-Bacterial Agents; Biofilms; Drug Design; Gallic Acid; Hexoses; Humans; Microbial Sensitivity Tests; Quorum Sensing; Staphylococcal Infections; Staphylococcus aureus; Structure-Activity Relationship; Vancomycin

Catheter-related bloodstream infections (CRBSIs) are common healthcare-associated infections associated with increased morbidity and medical costs. Antiseptic- and antibiotic-coated central venous catheters (CVCs) have been proposed to reduce the incidence of CRBSIs, with variable success. The aim of this study was to determine the in vivo antibiofilm activity of biocompatible and inexpensive compounds, such as cerium nitrate, chitosan and hamamelitannin, against usual agents of CRBSIs.. The antibiofilm effect of cerium nitrate, chitosan and hamamelitannin was tested against Staphylococcus epidermidis, Staphylococcus aureus, Acinetobacter baumannii and Candida albicans in a mouse foreign body infection model, using polyurethane catheter segments. Biofilm formation was assessed with a crystal violet assay to quantify the total biomass, with a tetrazolium reduction assay to quantify the metabolic activity and with scanning electron microscopy.. At subinhibitory concentrations, cerium nitrate significantly reduced biofilm formation by C. albicans, chitosan significantly decreased biofilm formation by S. epidermidis and C. albicans, and hamamelitannin significantly inhibited all bacterial biofilms.. The in vivo antibiofilm effect of cerium nitrate against C. albicans and of chitosan against C. albicans and S. epidermidis, at subinhibitory concentrations, makes them promising alternatives to coat CVCs. Moreover, the microbicidal effect on a wider range of CVC colonizers was previously reported in vitro for both compounds, at higher concentrations. For all bacterial strains, the highest in vivo antibiofilm efficacy was achieved with hamamelitannin. For A. baumannii, this is the first report of in vivo inhibition.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Infective Agents; Biofilms; Candida albicans; Candidiasis; Catheter-Related Infections; Cerium; Chitosan; Female; Gallic Acid; Hexoses; Mice; Mice, Inbred BALB C; Staphylococcal Infections; Staphylococcus epidermidis

Staphylococci are a major health threat because of increasing resistance to antibiotics. An alternative to antibiotic treatment is preventing virulence by inhibition of bacterial cell-to-cell communication using the quorum-sensing inhibitor RNAIII-inhibiting peptide (RIP). In this work, we identified 2',5-di-O-galloyl-d-hamamelose (hamamelitannin) as a nonpeptide analog of RIP by virtual screening of a RIP-based pharmacophore against a database of commercially available small-molecule compounds. Hamamelitannin is a natural product found in the bark of Hamamelis virginiana (witch hazel), and it has no effect on staphylococcal growth in vitro; but like RIP, it does inhibit the quorum-sensing regulator RNAIII. In a rat graft model, hamamelitannin prevented device-associated infections in vivo, including infections caused by methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis strains. These findings suggest that hamamelitannin may be used as a suppressor to staphylococcal infections.

Topics: Animals; Bacterial Adhesion; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Gallic Acid; Hemolysin Proteins; Hexoses; Male; Microbial Sensitivity Tests; Models, Molecular; Oligopeptides; Prosthesis-Related Infections; Quorum Sensing; Rats; Rats, Wistar; RNA, Bacterial; Staphylococcal Infections; Staphylococcus