curcumin and Pseudomonas-Infections

Due to increasing antimicrobial resistance, studies where new treatment options are investigated along with the synergistic effects of natural products with antibiotics have arisen. Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and infection with multi-drug resistant (MDR) P. aeruginosa poses a critical problem during treatment. Curcumin (CUR) is listed in the literature as one of the promising natural ingredients with its strong antimicrobial activity. In our study, our aim was to investigate the in vitro synergistic effect of CUR with imipenem (IMP) and Colistin (CST) in MDR P. aeruginosa isolates and in vivo activity on Galleria mellonella (G. mellonella) larvae. Three clinical isolates of MDR P. aeruginosa, which were determined to be phenotypically resistant to carbapenems, were used, and KPC and OXA48 resistance genes were determined by PCR method. The synergistic effect of CUR with antibiotics were investigated by the checkerboard method. Larval survival and bacterial load were compared with the in vivo study. In this study, IMP MIC values were significantly reduced (two to eight-fold decrease) in the presence of CUR, and partial synergy was observed. For CST, this value decreased two-fold. Bacterial load was evaluated to investigate the effect of antimicrobials during infection. While the CFUs increased over time in non-treated larvae as compared to the initial inoculum, bacterial load was significantly decreased for the groups treated with CUR, IMP and CST compared to the untreated group (p < 0.05). It was concluded CUR-antibiotic combinations can provide an alternative approach in the treatment of infections with MDR bacteria.

Topics: Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Curcumin; Drug Resistance, Multiple, Bacterial; Larva; Microbial Sensitivity Tests; Moths; Pseudomonas aeruginosa; Pseudomonas Infections

There persists a constant threat from multidrug resistance being acquired by all human pathogens that challenges the well-being of humans. This phenomenon is predominantly led by Pseudomonas aeruginosa which is already resistant to the current generations of antibiotic by altering its metabolic pathways to survive. Specifically for this microbe the phenomenon of quorum sensing (QS) plays a crucial role in acquiring virulence and pathogenicity. QS is simply the cross talk between the bacterial community driven by signals that bind to receptors, enabling the entire bacterial microcosm to function as a single unit which has led to control P. aeruginosa cumbersome even in presence of antibiotics. Inhibition of QS can, therefore, be of a significant importance to curb such virulent and pathogenic strains of P. aeruginosa. Natural compounds are well known for their antimicrobial properties, of which, information on their mode of action is scarce. There can be many antimicrobial phytochemicals that act by hindering QS-pathways. The rationale of the current study is to identify such natural compounds that can inhibit QS in P. aeruginosa driven by LasR, PhzR, and RhlR dependent pathways. To achieve this rationale, in silico studies were first performed to identify such natural compounds which were then validated by in vitro experiments. Gingerol and Curcumin were identified as QS-antagonists (QSA) which could further suppress the production of biofilm, EPS, pyocyanin, and rhamnolipid along with improving the susceptibility to antibiotics.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Catechols; Curcumin; Fatty Alcohols; Glycolipids; Microbial Sensitivity Tests; Molecular Dynamics Simulation; Phytochemicals; Pseudomonas aeruginosa; Pseudomonas Infections; Pyocyanine; Quorum Sensing; Signal Transduction; Trans-Activators; Virulence

Because of its diverse range of use in several ethics of diagnosis and care of multiple diseases, nanotechnology has seen remarkable growth and has become a key component of medical sciences. In recent years, there has been rapid advancement in medicine and biomaterials. Nanomedicine aids in illness prevention, diagnosis, monitoring, and treatment.. The purpose of this work is to evaluate the antibacterial, anti-inflammatory, and cytotoxic capabilities of green produced silver nanoparticle with the addition of curcumin-assisted chitosan nanocomposite (SCCN) against wound pathogenic as reducing agents.. The plant extract of. The produced silver nanoparticle with the addition of curcumin-assisted chitosan nanocomposite (SCCN) has significant antibacterial activities against. This advancement in the field of biomaterials, which means nanocomposite, not only helps to reduce the harmful effects of pathogenic organisms while representing an environmentally benign material but it also shows to be a material with zero danger to humans and the environment.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Biocompatible Materials; Cell Line, Tumor; Chitosan; Curcumin; Humans; Metal Nanoparticles; Millettia; Nanocomposites; Nanotechnology; Particle Size; Plant Extracts; Pseudomonas aeruginosa; Pseudomonas Infections; Silver; Staphylococcal Infections; Staphylococcus aureus; Wound Healing

Nowadays, the resistance of bacterial biofilms towards the available antibiotics is a severe problem. Therefore, many efforts were devoted to develop new formulations using nanotechnology. We have developed an inhalable microparticle formulation using spray-drying combining multiple drugs: an antibiotic (tobramycin, ciprofloxacin or azithromycin), N-acetylcysteine (NAC), and curcumin (Cur). The use of PLGA nanoparticles (NP) also allowed incorporating curcumin to facilitate spray drying and modify the release of some compounds. The aerosolizable microparticles formulations were characterized in terms of size, morphology, and aerodynamic properties. Biocompatibility when tested on macrophage-like cells was acceptable after 20 h exposure for concentrations up to at least 32 µg/mL. Antibacterial activity of free drugs versus drugs in the multiple drug formulations was evaluated on P. aeruginosa in the same range. When co-delivered the efficacy of tobramycin was enhanced compared to the free drug for the 1 µg/mL concentration. The combinations of azithromycin and ciprofloxacin with NAC and Cur did not show an improved antibacterial activity. Bacteria-triggered cytokine release was not inhibited by free antibiotics, except for TNF-α. In contrast, the application of NAC and the addition of curcumin-loaded PLGA NPs showed a higher potential to inhibit TNF-α, IL-8, and IL-1β release. Overall, the approach described here allows simultaneous delivery of antibacterial, mucolytic, and anti-inflammatory compounds in a single inhalable formulation and may therefore pave the way for a more efficient therapy of pulmonary infections.

Topics: Acetylcysteine; Administration, Inhalation; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Ciprofloxacin; Curcumin; Cytokines; Drug Carriers; Drug Combinations; Drug Compounding; Expectorants; Freeze Drying; Humans; Inflammation Mediators; Macrophages; Microbial Viability; Mucus; Nanoparticles; Permeability; Polylactic Acid-Polyglycolic Acid Copolymer; Pseudomonas aeruginosa; Pseudomonas Infections; THP-1 Cells; Tobramycin

The indiscriminate and excessive use of antibiotics has ultimately led to the emergence of bacterial resistant mutants or superbugs. These superbugs are difficult to control with conventional antibiotics. Disabling quorum sensing (QS), a population-density-dependent cell-to-cell communication process used by bacteria to coordinate the expression of virulence genes and biofilm formation, with dietary phytochemicals is emerging as a non-antibiotic strategy to inhibit bacterial pathogenicity. Although curcumin is an anti-QS agent and its delivery to cells has been a challenge due to poor bioavailability, ZnO/curcumin nanocomposites (ZnC-NCs) were fabricated with enhanced delivery of curcumin inside the bacterial superbug

Topics: Animals; Bacterial Proteins; Biofilms; Biological Availability; Curcumin; Delayed-Action Preparations; Disease Models, Animal; Drug Carriers; Drug Liberation; Epithelial Cells; Female; Humans; Mice; Microbial Sensitivity Tests; Nanocomposites; Pseudomonas aeruginosa; Pseudomonas Infections; Quorum Sensing; Trans-Activators; Zinc Oxide

Aminoglycoside antibiotics and imipenem are reported to stimulate exopolysaccharide alginate production and cause an increased biofilm volume in Pseudomonas aeruginosa. Recently, some remarkable studies have been conducted on the effects of curcumin (Turmeric), which is the fenolic form of Curcuma longa plant, on virulence factors of P.aeruginosa. In this study, we aimed to investigate the effects of MIC and sub-MIC concentrations of imipenem, tobramycin, and curcumin on biofilm formation of P.aeruginosa strains. P.aeruginosa strains (n= 2) used in this study were isolated from deep oropharyngeal swab samples of two cystic fibrosis patients. Antimicrobial susceptibilities of the two strains to imipenem, tobramycin, and curcumin were investigated by broth microdilution method, and biofilm production was assessed by using crystal violet staining method. In our study, MIC values of imipenem, tobramycin and curcumin for strain-1 were 8 µg/ml, 8 µg/ml and 16 µg/ml, respectively, while those values were 4 µg/ml, 8 µg/ml and 16 µg/ml for strain-2. Biofilm optical density values of the strain-1 and strain-2 before being treated with the test substances were 0.937 and 0.313 (control: 0.090), respectively, Biofilm optical densities of the both strains showed an increase following treatment with MIC concentrations of imipenem and tobramycin. The treatment of the strains with MIC and sub-MIC concentrations of curcumin led to no significant increase in biofilm optical density. The data obtained in this study supported the promising inhibitory effect of curcumin on P.aeruginosa biofilms. However, further more comprehensive studies are required to provide satisfactory data about the use of curcumin to treat P.aeruginosa infections characterized by biofilm formation.

Topics: Anti-Bacterial Agents; Biofilms; Curcumin; Cystic Fibrosis; Humans; Imipenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin