scholarly journals Photoinactivation Efficiency of Cationic Porphyrin Derivatives Against Multidrug-Resistant Wound Pathogens

2021 ◽  
Author(s):  
Ayşe AKBIYIK ◽  
Hüseyin TAŞLI ◽  
Nermin TOPALOĞLU ◽  
Vildan ALPTÜZÜN ◽  
Sülünay PARLAR ◽  
...  
Keyword(s):  
Energy Density ◽  
Bacterial Strain ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Cationic Porphyrin ◽  
Wound Model ◽  
Porphyrin Derivatives ◽  
High Concentrations

Abstract The photoinactivation efficiency of antimicrobial photodynamic therapy (aPDT) with cationic porphyrin derivatives (CPDs) against multidrug-resistant (MDR) bacterial strain was assessed. MDR bacterial strains including Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and Klebsiella pneumoniae were used. The CPDs named PM, PE, PN, and PL were synthesized as a photosensitizer (PS). A diode laser with a wavelength of 655 nm was used as a light source. Photoinactivation efficiency of the combinations formed with different energy density (50, 100, and 150 J/cm²) and PS concentrations (ranging from 3.125 µM and 600 µM) on each bacterial strain were evaluated. Toxicity of the aPDT combinations that showed a strong photoinactivation on the bacterial strains and dark toxicity of PSs and were evaluated on fibroblasts cells. In the aPDT experiments, survival reductions of up to 5.80 log₁₀ on E. coli, 5.90 log₁₀ on P. aeruginosa, 6.11 log₁₀ on K. pneumoniae and 6.78 log₁₀ on A. baumannii were obtained. There was an increase in the photoinactivation efficiency in parallel with increasing the energy density, and the best effect seen at an energy density of 150 J/cm2. PL did not show any toxic effect on fibroblasts. However, other PSs were toxic in fibroblasts at high concentrations. In this research, which reflected the results of in vitro experiments, aPDT provided potent photoinactivation against MDR clinical isolates. The research results lead to an in vivo wound model study of aPDT with CPD infected with an MDR clinical isolate.

scholarly journals Clavanin A Improves Outcome of Complications from Different Bacterial Infections

2014 ◽  
Vol 59 (3) ◽  
pp. 1620-1626 ◽  
Author(s):  
Osmar N. Silva ◽  
Isabel C. M. Fensterseifer ◽  
Elaine A. Rodrigues ◽  
Hortência H. S. Holanda ◽  
Natasha R. F. Novaes ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Toxicity Tests ◽  
Cytotoxic Activities ◽  
Content Type ◽  
Wound Model ◽  
Acute Toxicity Tests

ABSTRACTThe rapid increase in the incidence of multidrug-resistant infections today has led to enormous interest in antimicrobial peptides (AMPs) as suitable compounds for developing unusual antibiotics. In this study, clavanin A, an antimicrobial peptide previously isolated from the marine tunicateStyela clava, was selected as a purposeful molecule that could be used in controlling infection and further synthesized. Clavanin A wasin vitroevaluated againstStaphylococcus aureusandEscherichia colias well as toward L929 mouse fibroblasts and skin primary cells (SPCs). Moreover, this peptide was challenged here in anin vivowound and sepsis model, and the immune response was also analyzed. Despite displaying clearin vitroantimicrobial activity toward Gram-positive and -negative bacteria, clavanin A showed no cytotoxic activities against mammalian cells, and in acute toxicity tests, no adverse reaction was observed at any of the concentrations. Moreover, clavanin A significantly reduced theS. aureusCFU in an experimental wound model. This peptide also reduced the mortality of mice infected withE. coliandS. aureusby 80% compared with that of control animals (treated with phosphate-buffered saline [PBS]): these data suggest that clavanin A prevents the start of sepsis and thereby reduces mortality. These data suggest that clavanin A is an AMP that could improve the development of novel peptide-based strategies for the treatment of wound and sepsis infections.

scholarly journals In vivo capture of bacterial cells by remote guiding

2021 ◽  
Author(s):  
Iaroslav A. Rybkin ◽  
Sergey I. Pinyaev ◽  
Olga A. Sindeeva ◽  
Sergey V. German ◽  
Maja Koblar ◽  
...  
Keyword(s):  
Genetic Material ◽  
Local Concentration ◽  
Bacterial Cells ◽  
Bacterial Strains ◽  
Toxic Side Effect ◽  
High Concentrations ◽  
Strong Barrier ◽  
Growth Distribution

Recently, it has been shown that several bacterial strains can be very efficient in cancer treatment since they possess many important properties such as self-targeting, ease of detection, sensing and toxicity against tumors. However, there are only a few relevant candidates for such an approach, as targeting and detection one of the biggest challenges as well as there are many limitations in the use of genetic approaches. Here, it is proposed the solution that enables surface modification of alive bacterial cells without interfering with their genetic material and potentially reduces their toxic side effect. By the electrostatic interaction fluorescently labeled polyelectrolytes (PEs) and magnetite nanoparticles (NPs) were deposited on the bacterial cell surface to control the cell growth, distribution and detection of bacteria. According to the results obtained in vivo, by the magnet entrapment of the modified bacteria the local concentration of the cells was increased more than 5 times, keeping the high concentrations even when the magnet is removed. Since the PEs create a strong barrier, in vitro it was shown that the division time of the cells can be regulated for better immune presentation.

scholarly journals Infection Responsive Smart Delivery of Antibiotics Using Recombinant Spider Silk Nanospheres

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1358
Author(s):  
Pranothi Mulinti ◽  
Jacob Shreffler ◽  
Raquib Hasan ◽  
Michael Dea ◽  
Amanda E. Brooks
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Spider Silk ◽  
Popular Science ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Bacterial Strains ◽  
Antibiotic Drug

Frequent and inappropriate usage of antibiotics has changed the natural evolution of bacteria by reducing susceptibility and increasing resistance towards antibacterial agents. New resistance mechanisms evolved in the response to host defenses and pharmaceutical interventions are threatening our ability to treat common infections, resulting in increased mortality. In the face of this rising epidemic, antibiotic drug discovery, which has long been overlooked by big pharma, is reaching a critical low. Thus, the development of an infection-responsive drug delivery system, which may mitigate multidrug resistance and preserve the lifetime of our current antibiotic arsenal, has garnered the attention of both popular science and funding agencies. The present work describes the development of a thrombin-sensitive linker embedded into a recombinant spider silk copolymer to create a nanosphere drug delivery vehicle. Recent studies have suggested that there is an increase in thrombin-like activity during Staphylococcus aureus infection; thus, drug release from this new “smart” nanosphere can be triggered in the presence of infection. A thrombin sensitive peptide (TSP) was synthesized, and the thrombin cleavage sensitivity was determined by HPLC. The results showed no cleavage of the peptide when exposed to human serum whereas the peptide was cleaved when incubated with S. aureus exudate. Subsequently, the peptide was coupled with a silk copolymer via EDC-NHS chemistry and formulated into nanospheres encapsulating antibiotic vancomycin. These nanospheres were evaluated for in vitro infection-responsive drug release and antimicrobial activity. Finally, the drug responsive nanospheres were assessed for efficacy in an in vivo septic arthritis model. Our study provides evidence that the protein conjugate was enzyme responsive and can be used to formulate targeted drug release to combat infections against multidrug-resistant bacterial strains.

scholarly journals Synergistic Killing and Re-Sensitization of Pseudomonas aeruginosa to Antibiotics by Phage-Antibiotic Combination Treatment

2021 ◽  
Vol 14 (3) ◽  
pp. 184
Author(s):  
Emily Engeman ◽  
Helen R. Freyberger ◽  
Brendan W. Corey ◽  
Amanda M. Ward ◽  
Yunxiu He ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Combination Treatment ◽  
Multidrug Resistant ◽  
Wound Model ◽  
Colony Forming Units ◽  
Genes Encoding ◽  
Worm Model ◽  
Antibiotic Combination

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections pose a serious health threat. Bacteriophage–antibiotic combination therapy is a promising candidate for combating these infections. A 5-phage P. aeruginosa cocktail, PAM2H, was tested in combination with antibiotics (ceftazidime, ciprofloxacin, gentamicin, meropenem) to determine if PAM2H enhances antibiotic activity. Combination treatment in vitro resulted in a significant increase in susceptibility of MDR strains to antibiotics. Treatment with ceftazidime (CAZ), meropenem, gentamicin, or ciprofloxacin in the presence of the phage increased the number of P. aeruginosa strains susceptible to these antibiotics by 63%, 56%, 31%, and 81%, respectively. Additionally, in a mouse dorsal wound model, seven of eight mice treated with a combination of CAZ and PAM2H for three days had no detectable bacteria remaining in their wounds on day 4, while all mice treated with CAZ or PAM2H alone had ~107 colony forming units (CFU) remaining in their wounds. P. aeruginosa recovered from mouse wounds post-treatment showed decreased virulence in a wax worm model, and DNA sequencing indicated that the combination treatment prevented mutations in genes encoding known phage receptors. Treatment with PAM2H in combination with antibiotics resulted in the re-sensitization of P. aeruginosa to antibiotics in vitro and a synergistic reduction in bacterial burden in vivo.

scholarly journals Hybrid Pectin-Liposome Formulation against Multi-Resistant Bacterial Strains

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 769 ◽  
Author(s):  
Lígia Nunes de Morais Ribeiro ◽  
Eneida de Paula ◽  
Daise Aparecida Rossi ◽  
Guilherme Paz Monteiro ◽  
Edson Campos Valadares Júnior ◽  
...  
Keyword(s):  
In Vitro Release ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Toxicity Assay ◽  
Chicken Embryos ◽  
E Coli ◽  
Physicochemical Stability ◽  
Vitro Release

This work describes the development of a gastroresistant antimicrobial formulation composed of two carriers, pectin and liposomes, intended to improve the efficiency of norfloxacin (NOR) against multi-resistant bacterial strains. The formulations showed physicochemical stability for 180 days (4 °C) in terms of size, polydispersity, and zeta potential of the vesicles, prolonging the in vitro release of NOR for 11 h. The hybrid nanocarriers improved the in vitro antimicrobial activity against different multidrug-resistant bacterial strains, such as Salmonella sp., Pseudomonasaeruginosa, E. coli and Campylobacterjejuni, in comparison to commercial NOR and liposomal suspensions. The in vivo toxicity assay in chicken embryos revealed that the hybrid systems were not toxic in any of the different parameters analyzed, a result also corroborated by the analyses of biochemical biomarkers of the chicken-embryos liver function.

Effects of Probiotics in the Management of Infected Chronic Wounds: From Cell Culture to Human Studies

2020 ◽  
Vol 15 (3) ◽  
pp. 193-206
Author(s):  
Brognara Lorenzo ◽  
Salmaso Luca ◽  
Mazzotti Antonio ◽  
Di M. Alberto ◽  
Faldini Cesare ◽  
...  
Keyword(s):  
Chronic Wounds ◽  
Animal Experiments ◽  
Multidrug Resistant ◽  
Preliminary Evidence ◽  
Human Studies ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Keywords Probiotics

Background: Chronic wounds are commonly associated with polymicrobial biofilm infections. In the last years, the extensive use of antibiotics has generated several antibiotic-resistant variants. To overcome this issue, alternative natural treatments have been proposed, including the use of microorganisms like probiotics. The aim of this manuscript was to review current literature concerning the application of probiotics for the treatment of infected chronic wounds. Methods: Relevant articles were searched in the Medline database using PubMed and Scholar, using the keywords “probiotics” and “wound” and “injuries”, “probiotics” and “wound” and “ulcer”, “biofilm” and “probiotics” and “wound”, “biofilm” and “ulcer” and “probiotics”, “biofilm” and “ulcer” and “probiotics”, “probiotics” and “wound”. Results: The research initially included 253 articles. After removal of duplicate studies, and selection according to specific inclusion and exclusion criteria, 19 research articles were included and reviewed, accounting for 12 in vitro, 8 in vivo studies and 2 human studies (three articles dealing with animal experiments included also in vitro testing). Most of the published studies about the effects of probiotics for the treatment of infected chronic wounds reported a partial inhibition of microbial growth, biofilm formation and quorum sensing. Discussion: The application of probiotics represents an intriguing option in the treatment of infected chronic wounds with multidrug-resistant bacteria; however, current results are difficult to compare due to the heterogeneity in methodology, laboratory techniques, and applied clinical protocols. Lactobacillus plantarum currently represents the most studied strain, showing a positive application in burns compared to guideline treatments, and an additional mean in chronic wound infections. Conclusions: Although preliminary evidence supports the use of specific strains of probiotics in certain clinical settings such as infected chronic wounds, large, long-term clinical trials are still lacking, and further research is needed.

scholarly journals Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets

2020 ◽  
Vol 318 (1) ◽  
pp. G1-G9 ◽  
Author(s):  
Richard A. Jacobson ◽  
Kiedo Wienholts ◽  
Ashley J. Williamson ◽  
Sara Gaines ◽  
Sanjiv Hyoju ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Healing Process ◽  
Abdominal Sepsis ◽  
Infectious Complications ◽  
Fibrinolytic System ◽  
Clinical Safety ◽  
High Concentrations ◽  
Clinically Significant

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing. NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

scholarly journals Collagen-Based Electrospun Materials for Tissue Engineering: A Systematic Review

2021 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Britani N. Blackstone ◽  
Summer C. Gallentine ◽  
Heather M. Powell
Keyword(s):  
Systematic Review ◽  
Tissue Engineering ◽  
Collagen Type I ◽  
The Body ◽  
Pool Data ◽  
Type I ◽  
High Concentrations ◽  
Increased Strength

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures.

scholarly journals Synthesis, characterization, and pharmacological evaluation of thiourea derivatives

2020 ◽  
Vol 18 (1) ◽  
pp. 764-777
Author(s):  
Sumaira Naz ◽  
Muhammad Zahoor ◽  
Muhammad Naveed Umar ◽  
Saad Alghamdi ◽  
Muhammad Umar Khayam Sahibzada ◽  
...  
Keyword(s):  
Spectroscopic Techniques ◽  
Organosulfur Compounds ◽  
Bacterial Strains ◽  
Thiourea Derivatives ◽  
Toxicological Effects ◽  
Pharmaceutical Industries ◽  
Uv Visible ◽  
Hematological And Biochemical Parameters

AbstractThioureas and their derivatives are organosulfur compounds having applications in numerous fields such as organic synthesis and pharmaceutical industries. Symmetric thiourea derivatives were synthesized by the reaction of various anilines with CS2. The synthesized compounds were characterized using the UV-visible and nuclear magnetic resonance (NMR) spectroscopic techniques. The compounds were screened for in vitro inhibition of α-amylase, α-glucosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes and for their antibacterial and antioxidant potentials. These compounds were fed to Swiss male albino mice to evaluate their toxicological effects and potential to inhibit glucose-6-phosphatase (G6Pase) inhibition. The antibacterial studies revealed that compound 4 was more active against the selected bacterial strains. Compound 1 was more active against 2,2-diphenyl-1-picrylhydrazyl and 2,2’-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals, AChE, BuChE, and α-glucosidase. Compound 2 was more potent against α-amylase and G6Pase. Toxicity studies showed that compound 4 is safe as it exerted no toxic effect on any of the hematological and biochemical parameters or on liver histology of the experimental animals at any studied dose rate. The synthesized compounds showed promising antibacterial and antioxidant potential and were very active (both in vitro and in vivo) against G6Pase and moderately active against the other selected enzymes used in this study.

scholarly journals Silver Nanoparticles and Their Antibacterial Applications

2021 ◽  
Vol 22 (13) ◽  
pp. 7202
Author(s):  
Tamara Bruna ◽  
Francisca Maldonado-Bravo ◽  
Paul Jara ◽  
Nelson Caro
Keyword(s):  
Silver Nanoparticles ◽  
Antibacterial Agents ◽  
Multidrug Resistant ◽  
Secondary Effects ◽  
Cytotoxic Effects ◽  
Factors Affecting ◽  
Gram Positive Bacteria ◽  
Resistant Strains

Silver nanoparticles (AgNPs) have been imposed as an excellent antimicrobial agent being able to combat bacteria in vitro and in vivo causing infections. The antibacterial capacity of AgNPs covers Gram-negative and Gram-positive bacteria, including multidrug resistant strains. AgNPs exhibit multiple and simultaneous mechanisms of action and in combination with antibacterial agents as organic compounds or antibiotics it has shown synergistic effect against pathogens bacteria such as Escherichia coli and Staphylococcus aureus. The characteristics of silver nanoparticles make them suitable for their application in medical and healthcare products where they may treat infections or prevent them efficiently. With the urgent need for new efficient antibacterial agents, this review aims to establish factors affecting antibacterial and cytotoxic effects of silver nanoparticles, as well as to expose the advantages of using AgNPs as new antibacterial agents in combination with antibiotic, which will reduce the dosage needed and prevent secondary effects associated to both.

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