Antibacterial Activity of Surfactin and Synergistic Effect with Conventional Antibiotics Against Methicillin-Resistant Staphylococcus Aureus Isolated from Patients with Diabetic Foot Ulcers [Response to Letter].
Antibacterial Activity of Surfactin and Synergistic Effect with Conventional Antibiotics Against Methicillin-Resistant Staphylococcus Aureus Isolated from Patients with Diabetic Foot Ulcers [Response to Letter].
Project description:Penicillenol A2 (isolated from deep-sea fungus Penicillium biourgeianum DFFSCS023) has good antibacterial activity against methicillin-sensitive Staphylococcus aureus and in combination with beta-lactam antibiotics it could significantly decrease methicillin-resistant Staphylococcus aureus (MRSA) survival, which provides a novel treatment consideration for MRSA-caused infections.
Project description:Antibiotic resistance has become a serious global concern, and the discovery of antimicrobial herbal constituents may provide valuable solutions to overcome the problem. In this study, the effects of therapies combining antibiotics and four medicinal herbs on methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Specifically, the synergistic effects of Magnolia officinalis, Verbena officinalis, Momordica charantia, and Daphne genkwa in combination with oxacillin or gentamicin against methicillin-resistant (ATCC43300) and methicillin-susceptible (ATCC25923) S. aureus were examined. In vitro susceptibility and synergistic testing were performed to measure the minimum inhibitory concentration and fractional inhibitory concentration (FIC) index of the antibiotics and medicinal herbs against MRSA and methicillin-susceptible S. aureus. To identify the active constituents in producing these synergistic effects, in silico molecular docking was used to investigate the binding affinities of 139 constituents of the four herbs to the two common MRSA inhibitory targets, penicillin binding proteins 2a (PBP2a) and 4 (PBP4). The physicochemical and absorption, distribution, metabolism, and excretion properties and drug safety profiles of these compounds were also analyzed. D. genkwa extract potentiated the antibacterial effects of oxacillin against MRSA, as indicated by an FIC index value of 0.375. M. officinalis and V. officinalis produced partial synergistic effects when combined with oxacillin, whereas M. charantia was found to have no beneficial effects in inhibiting MRSA. Overall, tiliroside, pinoresinol, magnatriol B, and momorcharaside B were predicted to be PBP2a or PBP4 inhibitors with good drug-like properties. This study identifies compounds that deserve further investigation with the aim of developing therapeutic agents to modulate the effect of antibiotics on MRSA. Impact statement Antibiotic resistant is a well-known threat to global health and methicillin-resistant Staphylococcus aureus is one of the most significant ones. These resistant bacteria kill thousands of people every year and therefore a new effective antimicrobial treatment is necessary. This study identified the herbs and their associated bioactive ingredients that can potential the effects of current antibiotics. These herbs have long history of human usage in China and have well-defined monograph in the Chinese Pharmacopeia. These indicate their relatively high clinical safety and may have a quicker drug development process than that of a new novel antibiotic. Based on the results of this study, the authors will perform further in vitro and animal studies, aiming to accumulate significant data for the application of clinical trial.
Project description:Objective:To compare the effects of simple saline dressings versus topical vancomycin dressings on Methicillin-resistant Staphylococcus Aureus positive chronic diabetic foot ulcers. Methods:It was quasi experimental study conducted in Combined Military Hospital Kohat and PNS-Shifa Hospital Karachi from 01 January 2017 to 31 December 2017. A total of 23 patients were included based on non-probability convenient sampling who had diabetes and presented with foot ulcers for more than two weeks showing positive growth of Methicillin-Resistant Staphylococcus Aureus. The patients were treated with simple saline soaked dressings and debridement at first for three weeks followed by three weeks of topical vancomycin dressings with debridement. Thus patients served as their own controls. Results:The average change in surface area with saline dressing was +1.73 ±1.53cm2 per week whereas with vancomycin soaked dressing it was --0.06±1.60 cm2 per week (p <0.05). The average exudate also decreased from 1.78±1.23 to 0.99±0.72 (p<0.05) and same trend was observed in percentage of slough covering the ulcer from 45% ± 22.3% to 24.3% ±12.90% (p<0.05) with vancomycin dressing. Moreover, fifteen patients had negative culture for MRSA within 2 weeks. Conclusion:Vancomycin impregnated dressing in MRSA positive Diabetic foot may help achieve early healing as compared to simple conventional dressings with no systemic toxicity.
Project description:Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections.
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is drug-resistant and biofilm-forming pathogenic bacteria with severe morbidity and mortality, and has been continuously detected in food products in recent years. Mannosylerythritol lipids (MELs) are novel biosurfactants and perform antibacterial property against gram-positive bacteria. Ultrasound has been applied into food sterilization as non-thermal techniques and has advantage of maintaining food nutrition and flavor over heat pasteurization. In this work, the synergistic treatment of ultrasound and MEL-A was used to combat planktonic cells and biofilm of MRSA. As a result, the combined treatment has exhibited remarkable antibacterial effect proved by enumeration of viable microbes. Furthermore, flow cytometry, scanning electron microscopy and transmission electron microscopy revealed ultrasound has enhanced the inhibitory effect of MEL-A through exacerbating cell membrane damage. On the other hand, the collaborating working modes to eradicate MRSA biofilm were disturbing cell adhesion to surface by MEL-A and destructing mature biofilm mechanically by ultrasound, reaching to over 90% of clearance rate. The findings of this study illustrated the synergistic antimicrobial mechanism of ultrasound and MEL-A treatments, and offered theoretical basis for their potential applications in food preservation.
Project description:The improper use of antibiotics has led to the development of bacterial resistance, resulting in fewer antibiotics for many bacterial infections. Especially, the drug resistance of hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) is distinctly serious. This research designed and synthesized two series of 3-substituted ocotillol derivatives in order to improve their anti-HA-MRSA potency and synergistic antibacterial activity. Among the synthesized compounds, 20-31 showed minimum inhibitory concentration (MIC) values of 1-64 µg/mL in vitro against HA-MRSA 18-19, 18-20, and S. aureus ATCC29213. Compound 21 showed the best antibacterial activity, with an MIC of 1 μg/mL and had synergistic inhibitory effects. The fractional inhibitory concentration index (FICI) value was 0.375, when combined with chloramphenicol (CHL) or kanamycin (KAN). The structure-activity relationships (SARs) of ocotillol-type derivatives were also summarized. Compound 21 has the potential to be developed as a novel antibacterial agent or potentiator against HA-MRSA.
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) often cause infections with high mortality rates. Antimicrobial peptides are a source of molecules for developing antimicrobials; one such peptide is melittin, a fraction from the venom of the Apis mellifera bee. This study aimed to evaluate the antibacterial and antibiofilm activities of melittin and its association with oxacillin (mel+oxa) against MRSA isolates, and to investigate the mechanisms of action of the treatments on MRSA. Minimum inhibitory concentrations (MICs) were determined, and synergistic effects of melittin with oxacillin and cephalothin were assessed. Antibiofilm and cytotoxic activities, as well as their impact on the cell membrane, were evaluated for melittin, oxacillin, and mel+oxa. Proteomics evaluated the effects of the treatments on MRSA. Melittin mean MICs for MRSA was 4.7 μg/mL and 12 μg/mL for oxacillin. Mel+oxa exhibited synergistic effects, reducing biofilm formation, and causing leakage of proteins, nucleic acids, potassium, and phosphate ions, indicating action on cell membrane. Melittin and mel+oxa, at MIC values, did not induce hemolysis and apoptosis in HaCaT cells. The treatments resulted in differential expression of proteins associated with protein synthesis and energy metabolism. Mel+oxa demonstrated antibacterial activity against MRSA, suggesting a potential as a candidate for the development of new antibacterial agents against MRSA.
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most dreadful pathogens relevant in community and nosocomial-related infections around the world. Resensitising MRSA to antibiotics, once it became resistant, was a tough choice due to the high adaptability of this bacteria to savage conditions. This study aimed to create a chimeric enzybiotic against MRSA and test its efficiency, either individually or in combination with antibiotics. The novel enzybiotic BAC100 was constructed by fusing the catalytic domain from the bacteriocin BacL1 from Enterococcus faecalis with the cell-wall-binding domain from protein P17 of Staphylococcus aureus bacteriophage ϕ44AHJD. Apart from its partial lone activity, BAC100 was found to resensitise the MRSA strain to traditional antibiotics, including ampicillin and tetracycline. Both drugs were able to reduce live MRSA cells by 85 and 90%, respectively, within 60 min of treatment together with BAC100. However, no significant activity was observed against MRSA when these drugs were tested independently, pointing to the inherent resistance of MRSA against these conventional antibiotics. To our knowledge, this is one of the first instances where an engineered enzybiotic was found to resensitise MRSA to conventional antibiotics. This study will pave the way for the development of similar peptides that can be used together with antibiotics against gruesome pathogens of clinical importance.
Project description:There is an urgent need for the development of new antibiotics. Here, we describe the inhibitory activity of new quinone compounds against methicillin-resistant Staphylococcus aureus (ATCC® 43300), methicillin-sensitive S. aureus (ATCC® 29213), and two clinical isolates from Chile (ISP-213 and ISP-214). We observed 99.9% reduction in viability within 2 h of exposure without the cultures exhibiting any post-antibiotic effect, which was twice the kinetics to that observed with vancomycin. These clinical isolates did not acquire resistance to these quinone derivatives during the course of our study. We found that these compounds protected larvae of the greater wax moth, sp. Galleria mellonella, from infection by these MRSA clinical strains as effectively as vancomycin. These quinone derivatives are potential drug candidates worth further development.