ABSTRACT
Curcumin serves as a photosensitizer (PS) in the context of microbial inactivation when subjected to light exposure, to produce reactive oxygen species, which exhibit efficacy in eradicating microorganisms. This remarkable property underscores the growing potential of antimicrobial photodynamic therapy (aPDT) in the ongoing fight against bacterial infections. Considering this, we investigate the efficacy of various in vitro curcumin formulations within a PDT protocol designed to target Staphylococcus aureus. Specifically, we conduct a comparative analysis involving synthetic curcumin (Cur-Syn) and curcumin derivatives modified with chlorine (Cl), selenium (Se), and iodine (I) (Cur-Cl, Cur-Se, Cur-I). To assess the impact of aPDT, we subject S. aureus to incubation with curcumin, followed by irradiation at 450 nm with energy doses of 3.75, 7.5, and 15 J/cm2. Our investigation encompasses an evaluation of PS uptake and photobleaching across the various curcumin variants. Notably, all three modifications (Cur-Cl, Cur-Se, Cur-I) induce a significant reduction in bacterial viability, approximately achieving a 3-log reduction. Interestingly, the uptake kinetics of Cur-Syn and Cur-Se exhibit similarities, reaching saturation after 20 min. Our findings suggest that modifications to curcumin have a discernible impact on the photodynamic properties of the PS molecule.
ABSTRACT
FTIR (Fourier transform infrared spectroscopy) is one analytical technique of the absorption of infrared radiation. FTIR can also be used as a tool to characterize profiles of biomolecules in bacterial cells, which can be useful in differentiating different bacteria. Considering that different bacterial species have different molecular compositions, it will then result in unique FTIR spectra for each species and even bacterial strains. Having this important tool, here, we have developed a methodology aimed at refining the analysis and classification of the FTIR absorption spectra obtained from samples of Staphylococcus aureus, with the implementation of machine learning algorithms. In the first stage, the system conforming to four specified species groups, Control, Amoxicillin induced (AMO), Gentamicin induced (GEN), and Erythromycin induced (ERY), was analyzed. Then, in the second stage, five hidden samples were identified and correctly classified as with/without resistance to induced antibiotics. The total analyses were performed in three windows, Carbohydrates, Fatty Acids, and Proteins, of five hundred spectra. The protocol for acquiring the spectral data from the antibiotic-resistant bacteria via FTIR spectroscopy developed by Soares et al. was implemented here due to demonstrating high accuracy and sensitivity. The present study focuses on the prediction of antibiotic-induced samples through the implementation of the hierarchical cluster analysis (HCA), principal component analysis (PCA) algorithm, and calculation of confusion matrices (CMs) applied to the FTIR absorption spectra data. The data analysis process developed here has the main objective of obtaining knowledge about the intrinsic behavior of S. aureus samples within the analysis regions of the FTIR absorption spectra. The results yielded values with 0.7 to 1 accuracy and high values of sensitivity and specificity for the species identification in the CM calculations. Such results provide important information on antibiotic resistance in samples of S. aureus bacteria for potential application in the detection of antibiotic resistance in clinical use.
ABSTRACT
Multidrug-resistant bacteria are one of the most serious threats to infection control. Few new antibiotics have been developed; however, the lack of an effective new mechanism of their action has worsened the situation. Photodynamic inactivation (PDI) can break antimicrobial resistance, since it potentiates the effect of antibiotics, and induces oxidative stress in microorganisms through the interaction of light with a photosensitizer. This paper addresses the application of PDI for increasing bacterial susceptibility to antibiotics and helping in bacterial persistence and virulence. The effect of photodynamic action on resistant bacteria collected from patients and bacteria cells with induced resistance in the laboratory was investigated. Staphylococcus aureus resistance breakdown levels for each antibiotic (amoxicillin, erythromycin, and gentamicin) from the photodynamic effect (10 µM curcumin, 10 J/cm2) and its maintenance in descendant microorganisms were demonstrated within five cycles after PDI application. PDI showed an innovative feature for modifying the degree of bacterial sensitivity to antibiotics according to dosages, thus reducing resistance and persistence of microorganisms from standard and clinical strains. We hypothesize a reduction in the degree of antimicrobial resistance through photooxidative action combats antibiotic failures.
Subject(s)
Amoxicillin , Anti-Bacterial Agents , Humans , Anti-Bacterial Agents/pharmacology , Erythromycin , Gentamicins/pharmacology , BacteriaABSTRACT
Antibiotic failures in treatments of bacterial infections from resistant strains have been a global health concern, mainly due to the proportions they can reach in the coming years. Making microorganisms susceptible to existing antibiotics is an alternative to solve this problem. This study applies a physicochemical method to the standard treatment for modulating the synergistic response towards circumventing the mechanisms of bacterial resistance. Photodynamic inactivation protocols (curcumina 10 µM, 10 J/cm2) and their cellular behavior in the presence of amoxicillin, erythromycin, and gentamicin antibiotics were analyzed from the dynamics of bacterial interaction of a molecule that produces only toxic effects after the absorption of a specific wavelength of light. In addition to bacterial viability, the interaction of curcumin, antibiotics and bacteria were imaged and chemically analyzed using confocal fluorescence microscopy and Fourier-transform infrared spectroscopy (FTIR). The interaction between therapies depended on the sequential order of application, metabolic activity, and binding of bacterial cell surface biomolecules. The results demonstrated a potentiating effect of the antibiotic with up to to 32-fold reduction in minimum inhibitory concentrations and mean reductions of 7 log CFU/ml by physicochemical action at bacterial level after the photodynamic treatment. The changes observed as a result of bacteria-antibiotic interactions, such as membrane permeabilization and increase in susceptibility, may be a possibility for solving the problem of microbial multidrug resistance.
Subject(s)
Anti-Bacterial Agents , Bacteria , Anti-Bacterial Agents/pharmacologyABSTRACT
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.
Subject(s)
Drug Resistance, Microbial , Methicillin-Resistant Staphylococcus aureus , Photochemotherapy , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/drug effects , Drug Resistance, Microbial/radiation effects , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/radiation effects , Photosensitizing Agents/pharmacology , Reactive Oxygen Species/pharmacologyABSTRACT
The emergence of new microorganisms with resistance to current antimicrobials is one of the key issues of modern healthcare that must be urgently addressed with the development of new molecules and therapies. Photodynamic inactivation (PDI) in combination with antibiotics has been recently regarded as a promising wide-spectrum therapy for the treatment of localized topical infections. However, further studies are required regarding the selection of the best photosensitizer structures and protocol optimization, in order to maximize the efficiency of this synergic interaction. In this paper, we present results that demonstrate the influence of the structure of cationic imidazolyl-substituted photosensitizers and light on the enhancement of ciprofloxacin (CIP) activity, for the inactivation of Escherichia coli. Structure-activity studies have highlighted the tetra cationic imidazolyl porphyrin IP-H-Me4+ at sub-bactericide concentrations (4-16 nM) as the most promising photosensitizer for combination with sub-inhibitory CIP concentration (<0.25 mg/L). An optimized dual phototherapy protocol using this photosensitizer was translated to in vivo studies in mice wounds infected with E. coli. This synergic combination reduced the amount of photosensitizer and ciprofloxacin required for full E. coli inactivation and, in both in vitro and in vivo studies, the combination therapy was clearly superior to each monotherapy (PDI or ciprofloxacin alone). Overall, these findings highlight the potential of cationic imidazolyl porphyrins in boosting the activity of antibiotics and lowering the probability of resistance development, which is essential for a sustainable long-term treatment of infectious diseases.
Subject(s)
Escherichia coli Infections , Porphyrins , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cations/chemistry , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Escherichia coli , Escherichia coli Infections/drug therapy , Mice , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Phototherapy , Porphyrins/chemistry , Porphyrins/pharmacology , Porphyrins/therapeutic useABSTRACT
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.
ABSTRACT
Objectives: To estimate the prevalence of internet gaming disorder (IGD) and associated risk factors in a sample of secondary and postsecondary students from a public federal institution of higher education (Instituto Federal de Educação, Ciência e Tecnologia) in Southern Brazil. Methods: The study included a sociodemographic questionnaire, the Beck Depression Inventory (BDI), Self-Report Questionnaire (SRQ-20), Pittsburgh Sleep Quality Index (PSQI-BR), the Mini-Social Phobia Inventory (Mini-SPIN), and the Game Addiction Scale (GAS). Finally, IGD was measured with the Brazilian version of the Internet Gaming Disorder Scale-Short-Form (IGDS9-SF), which has been psychometrically validated in this population. Results: Overall, 38.2% (n=212) of the sample exhibited IGD symptoms, with 18.2% (n=101) being classed as at-risk gamers. Regression analysis found IGD to be associated with male gender, severe depressive symptoms, poor sleep quality, increased time spent gaming, and total free time spent gaming (p < 0.001). Conclusions: The prevalence of IGD in this sample was relatively high, and associated risk factors found were similar to those previously reported in the literature. Further studies investigating the epidemiology of IGD in Brazilian samples are warranted to better understand treatment needs and inform preventive measures in this population.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Young Adult , Behavior, Addictive/epidemiology , Video Games/adverse effects , Internet , Socioeconomic Factors , Brazil/epidemiology , Prevalence , Surveys and Questionnaires , Risk Factors , Behavior, Addictive/psychologyABSTRACT
OBJECTIVES: To estimate the prevalence of internet gaming disorder (IGD) and associated risk factors in a sample of secondary and postsecondary students from a public federal institution of higher education (Instituto Federal de Educação, Ciência e Tecnologia) in Southern Brazil. METHODS: The study included a sociodemographic questionnaire, the Beck Depression Inventory (BDI), Self-Report Questionnaire (SRQ-20), Pittsburgh Sleep Quality Index (PSQI-BR), the Mini-Social Phobia Inventory (Mini-SPIN), and the Game Addiction Scale (GAS). Finally, IGD was measured with the Brazilian version of the Internet Gaming Disorder Scale-Short-Form (IGDS9-SF), which has been psychometrically validated in this population. RESULTS: Overall, 38.2% (n=212) of the sample exhibited IGD symptoms, with 18.2% (n=101) being classed as at-risk gamers. Regression analysis found IGD to be associated with male gender, severe depressive symptoms, poor sleep quality, increased time spent gaming, and total free time spent gaming (p < 0.001). CONCLUSIONS: The prevalence of IGD in this sample was relatively high, and associated risk factors found were similar to those previously reported in the literature. Further studies investigating the epidemiology of IGD in Brazilian samples are warranted to better understand treatment needs and inform preventive measures in this population.