RESUMEN
The widespread use of antibiotics drives the evolution of antimicrobial-resistant bacteria (ARB), threatening patients and healthcare professionals. Therefore, the development of novel strategies to combat resistance is recognized as a global healthcare priority. The two methods to combat ARB are development of new antibiotics or reduction in existing resistances. Development of novel antibiotics is a laborious and slow-progressing task that is no longer a safe reserve against looming risks. In this research, we suggest a method for reducing resistance to extend the efficacious lifetime of current antibiotics. Antimicrobial photodynamic therapy (aPDT) is used to generate reactive oxygen species (ROS) via the photoactivation of a photosensitizer. ROS then nonspecifically damage cellular components, leading to general impairment and cell death. Here, we test the hypothesis that concurrent treatment of bacteria with antibiotics and aPDT achieves an additive effect in the elimination of ARB. Performing aPDT with the photosensitizer methylene blue in combination with antibiotics chloramphenicol and tetracycline results in significant reductions in resistance for two methicillin-resistant Staphylococcus aureus (MRSA) strains, USA300 and RN4220. Additional resistant S. aureus strain and antibiotic combinations reveal similar results. Taken together, these results suggest that concurrent aPDT consistently decreases S. aureus resistance by improving susceptibility to antibiotic treatment. In turn, this development exhibits an alternative to overcome some of the growing MRSA challenge.
Asunto(s)
Farmacorresistencia Microbiana , Staphylococcus aureus Resistente a Meticilina , Fotoquimioterapia , Antibacterianos/farmacología , Farmacorresistencia Microbiana/efectos de los fármacos , Farmacorresistencia Microbiana/efectos de la radiación , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de la radiación , Fármacos Fotosensibilizantes/farmacología , Especies Reactivas de Oxígeno/farmacologíaRESUMEN
Amyloid-Detection and imaging of amyloid-ß plaques (Aß) has been a focus in the field of neurodegeneration (ND) due to the high correlation with Parkinson's and Alzheimer's diseases. Here, a novel approach is being proposed and developed to induce and assess those diseases. Photodynamic therapy (PDT) is applied to the fruit fly Drosophila melanogaster as a model of systemic oxidative stress to induce rapid Aß accumulation. Excised brains are evaluated by Brillouin-Raman spectroscopy and microscopy with UV surface emissions (MUSE) to interrogate physical property changes due to fixation and high-dose PDT. MUSE reveals reasonable autofluorescence in the spectral range of Aß, particularly for females, with increased signal once stained. A presence of significant mechanical changes in fresh brains treated with PDT compared to healthy controls is revealed using Brillouin spectroscopy. Aß plaque presence was confirmed with confocal analysis, with female PDT flies yielding nearly four-fold the mean intensity of controls, thus marking PDT as a potential neurodegenerative disease model. MUSE may serve as a viable early screening method for Aß presence and quantification in a research setting. This reduces the time for sample preparation and drastically decreases the cost of Aß quantification.
RESUMEN
Soft matter implants are a rapidly growing field in medicine for reconstructive surgery, aesthetic treatments, and regenerative medicine. Though these procedures are efficacious, all implants carry risks associated with microbial infection which are often aggressive. Preventative and responsive measures exist but are limited in applicability to soft materials. Photodynamic therapy (PDT) presents a means to perform safe and effective antimicrobial treatments in proximity to soft implants. HEMA-DMAEMA hydrogels are prepared with the photosensitizer methylene blue included at 10 and 100 µM in solution used for swelling over 2 or 4 days. Thirty minutes or 5 h of LED illumination at 9.20 m W c m 2 $9.20\frac{{mW}}{{c{m}^2}}$ is then used for PDT-induced generation of reactive oxygen species in direct contact with hydrogels to test viable limits of treatment. Frequency sweep rheological measurements reveal minimal overall changes in terms of loss modulus and loss factor but a statistically significant drop in storage modulus for some PDT doses, though within the range of controls and biological variation. These mild impacts suggest the feasibility of PDT application for infection clearing in proximity to soft implants. Future investigation with additional hydrogel varieties and current implant models will further detail the safety of PDT in implant applications.
Asunto(s)
Fotoquimioterapia , Fotoquimioterapia/métodos , Hidrogeles/farmacología , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Metacrilatos , Azul de Metileno/farmacologíaRESUMEN
Antibiotic-resistant bacteria, which are growing at a frightening rate worldwide, has put the world on a long-standing alert. The COVID-19 health crisis reinforced the pressing need to address a fast-developing pandemic. To mitigate these health emergencies and prevent economic collapse, cheap, practical, and easily applicable infection control techniques are essential worldwide. Application of light in the form of photodynamic action on microorganisms and viruses has been growing and is now successfully applied in several areas. The efficacy of this approach has been demonstrated in the fight against viruses, prompting additional efforts to advance the technique, including safety use protocols. In particular, its application to suppress respiratory tract infections and to provide decontamination of fluids, such as blood plasma and others, can become an inexpensive alternative strategy in the fight against viral and bacterial infections. Diverse early treatment methods based on photodynamic action enable an accelerated response to emerging threats prior to the availability of preventative drugs. In this review, we evaluate a vast number of photodynamic demonstrations and first-principle proofs carried out on viral control, revealing its potential and encouraging its rapid development toward safe clinical practice. This review highlights the main research trends and, as a futuristic exercise, anticipates potential situations where photodynamic treatment can provide a readily available solution.