Biofunctionalized nano-antimicrobials - progress, prospects and challenges

2021 ◽  
Vol 22 ◽  
Author(s):  
Lutfur Rahman ◽  
Sabahat Asif ◽  
Ata Ullaha ◽  
Waheed S. Khan ◽  
Asma Rehman
Keyword(s):  
Side Effects ◽  
Natural Product ◽  
Metal Oxide Nanoparticles ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Minimal Inhibitory Concentrations ◽  
Metal Metal ◽  
Conventional Antibiotics ◽  
Rapid Emergence

Abstract: The rapid emergence of multidrug resistant bacterial strains clearly highlights the need for the development of new antimicrobial compounds/materials to address associated healthcare challenges. Meanwhile, the adverse side effects of conventional antibiotics on human health urge the development of new natural product-based antimicrobials to minimize the side effects. In this respect, we concisely review the recent scientific contributions to develop natural product-based nano-antibiotics. The focus of the review is on the use of flavonoids, peptides, and cationic biopolymer functionalized metal/metal oxide nanoparticles as efficient tools to hit the MDR bacterial strains. It summarizes the most recent aspects of the functionalized nanoparticles against various pathogenic bacterial strains with respect to their minimal inhibitory concentrations and mechanism of action at the cellular and molecular levels. At the end, the future perspectives to materialize the in vivo applications of nano-antimicrobials are suggested on the basis of the available research.

Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for Sustainable Medicine?

2018 ◽  
Vol 25 (21) ◽  
pp. 2503-2519 ◽  
Author(s):  
Anne Kokel ◽  
Marianna Torok
Keyword(s):  
Side Effects ◽  
Antimicrobial Peptides ◽  
Potential Drug ◽  
Green Technologies ◽  
Specific Antibodies ◽  
Structural Modifications ◽  
Drug Candidates ◽  
Induce Resistance ◽  
Conventional Antibiotics

Background: Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. Methods: In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. Results: As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Conclusion: Although further research is needed taking into account both environmental and human health consequences of novel AMPs, several of these compounds are promising drug candidates for use in sustainable medicine.

scholarly journals The application prospect of metal/metal oxide nanoparticles in the treatment of osteoarthritis

2021 ◽  
Vol 394 (10) ◽  
pp. 1991-2002
Author(s):  
Junchao Luo ◽  
Yin Zhang ◽  
Senbo Zhu ◽  
Yu Tong ◽  
Lichen Ji ◽  
...  
Keyword(s):  
Metal Oxide ◽  
Metal Oxide Nanoparticles ◽  
Biological Response ◽  
Cell Uptake ◽  
Oxide Nanoparticles ◽  
Therapeutic Effects ◽  
Superoxide Anions ◽  
Metal Metal ◽  
Cartilage Wear

AbstractThe current understanding of osteoarthritis is developing from a mechanical disease caused by cartilage wear to a complex biological response involving inflammation, oxidative stress and other aspects. Nanoparticles are widely used in drug delivery due to its good stability in vivo and cell uptake efficiency. In addition to the above advantages, metal/metal oxide NPs, such as cerium oxide and manganese dioxide, can also simulate the activity of antioxidant enzymes and catalyze the degradation of superoxide anions and hydrogen peroxide. Degrading of metal/metal oxide nanoparticles releases metal ions, which may slow down the progression of osteoarthritis by inhibiting inflammation, promoting cartilage repair and inhibiting cartilage ossification. In present review, we focused on recent research works concerning osteoarthritis treating with metal/metal oxide nanoparticles, and introduced some potential nanoparticles that may have therapeutic effects.

scholarly journals A molecular architectural design that promises potent antimicrobial activity against multidrug-resistant pathogens

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Bing Yuan ◽  
Jiaojiao Liu ◽  
Zhixiong Deng ◽  
Lin Wei ◽  
Wenwen Li ◽  
...  
Keyword(s):  
Architectural Design ◽  
Building Blocks ◽  
Multidrug Resistant ◽  
In Vitro Cytotoxicity ◽  
Antimicrobial Drugs ◽  
Minimal Inhibitory Concentrations ◽  
Antimicrobial Efficiency ◽  
Multidrug Resistant Pathogens

AbstractAddressing the devastating threat of drug-resistant pathogens requires the discovery of new antibiotics with advanced action mechanisms and/or novel strategies for drug design. Herein, from a biophysical perspective, we design a class of synthetic antibacterial complexes with specialized architectures based on melittin (Mel), a natural antimicrobial peptide, and poly(ethylene glycol) (PEG), a clinically available agent, as building blocks that show potent and architecture-modulated antibacterial activity. Among the complexes, the flexibly linear complex consisting of one Mel terminally connected with a long-chained PEG (e.g., PEG12k–1*Mel) shows the most pronounced improvement in performance compared with pristine Mel, with up to 500% improvement in antimicrobial efficiency, excellent in vitro activity against multidrug-resistant pathogens (over a range of minimal inhibitory concentrations of 2–32 µg mL−1), a 68% decrease in in vitro cytotoxicity, and a 57% decrease in in vivo acute toxicity. A lipid-specific mode of action in membrane recognition and an accelerated “channel” effect in perforating the bacterial membrane of the complex are described. Our results introduce a new way to design highly efficient and low-toxicity antimicrobial drugs based on architectural modulations with clinically available agents.

scholarly journals Antimicrobial Activity of Cyclic-Monomeric and Dimeric Derivatives of the Snail-Derived Peptide Cm-p5 against Viral and Multidrug-Resistant Bacterial Strains

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 745
Author(s):  
Melaine González-García ◽  
Fidel Morales-Vicente ◽  
Erbio Díaz Pico ◽  
Hilda Garay ◽  
Daniel G. Rivera ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Antifungal Activity ◽  
Multidrug Resistant ◽  
Moderate Activity ◽  
Dependent Manner ◽  
Bacterial Strains ◽  
Acinetobacter Baumanii ◽  
Concentration Dependent Manner ◽  
Conventional Antibiotics

Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum β-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25–50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.

Antimicrobial peptides: an overview of a promising class of therapeutics

2007 ◽  
Vol 2 (1) ◽  
pp. 1-33 ◽  
Author(s):  
Andrea Giuliani ◽  
Giovanna Pirri ◽  
Silvia Nicoletto
Keyword(s):  
Antimicrobial Peptides ◽  
Multidrug Resistant ◽  
Innate Immune ◽  
Resistant Bacteria ◽  
Yeast Fungi ◽  
Wide Range ◽  
New Development ◽  
Catheter Site ◽  
Conventional Antibiotics

AbstractAntibiotic resistance is increasing at a rate that far exceeds the pace of new development of drugs. Antimicrobial peptides, both synthetic and from natural sources, have raised interest as pathogens become resistant against conventional antibiotics. Indeed, one of the major strengths of this class of molecules is their ability to kill multidrug-resistant bacteria. Antimicrobial peptides are relatively small (6 to 100 aminoacids), amphipathic molecules of variable length, sequence and structure with activity against a wide range of microorganisms including bacteria, protozoa, yeast, fungi, viruses and even tumor cells. They usually act through relatively non-specific mechanisms resulting in membranolytic activity but they can also stimulate the innate immune response. Several peptides have already entered pre-clinical and clinical trials for the treatment of catheter site infections, cystic fibrosis, acne, wound healing and patients undergoing stem cell transplantation. We review the advantages of these molecules in clinical applications, their disadvantages including their low in vivo stability, high costs of production and the strategies for their discovery and optimization.

scholarly journals Optimised Genetic Tools Allow the Biosynthesis of Glycocin F and Analogues Designed to Test the Roles of Gcc Cluster Genes in Bacteriocin Production.

2021 ◽  
Author(s):  
Brittany J. Drummond ◽  
Trevor S. Loo ◽  
Mark L. Patchett ◽  
Gillian E. Norris
Keyword(s):  
Gene Expression ◽  
Antimicrobial Agents ◽  
Response Regulator ◽  
Shuttle Vector ◽  
Multidrug Resistant ◽  
Target Range ◽  
Efficient Production ◽  
Bacterial Strains ◽  
Natural Product Research

The emergence of multidrug-resistant pathogens has motivated natural product research to inform the development of new antimicrobial agents. Glycocin F (GccF) is a diglycosylated 43-amino acid bacteriocin secreted by Lactobacillus plantarum KW30. It displays a moderate phylogenetic target range that includes vancomycin-resistant strains of Enterococcus species and appears to have a novel bacteriostatic mechanism, rapidly inhibiting growth of the most susceptible bacterial strains at pM concentrations. Experimental verification of the predicted role(s) of gcc cluster genes in GccF biosynthesis has been hampered by the inability to produce soluble recombinant Gcc proteins. Here we report the development of pRV610gcc, an easily modifiable 11.2 kbp plasmid that enables the production of GccF in L. plantarum NC8. Gcc gene expression relies on native promoters in the cloned cluster, and NC8 pRV610gcc produces mature GccF at levels similar to KW30. Key findings are that: the glycosyltransferase glycosylates both serine and cysteine at either position in the sequence, but glycosylation of the loop serine is both sequence and spatially specific; glycosylation of the peptide scaffold is not required for export and subsequent disulfide bond formation; neither of the putative thioredoxin proteins is essential for peptide maturation; removal of the entire putative response regulator GccE decreases GccF production less than removal of the LytTR domain alone. Using this system, we have verified the functions of most of the gcc genes and have advanced our understanding of the roles of GccF structure in its maturation and antibacterial activity. IMPORTANCE The entire 7-gene cluster for the diglycosylated bacteriocin glycocin F (GccF), including the natural promoters responsible for gcc gene expression, has been ligated into the E. coli-LAB shuttle vector pRV610 to produce the easily modifiable 11.2 kbp plasmid pRV610gcc for the efficient production of glycocin F analogues. In contrast to the refactoring approach, chemical synthesis, or chemoenzymatic synthesis, all of which have been successfully used to probe glycocin structure and function, this plasmid can also be used to probe in vivo the evolutionary constraints on glycocin scaffolds and their processing by the maturation pathway machinery, thus increasing understanding of the enzymes involved, the order in which they act and how they are regulated.

scholarly journals Synergistic Therapies as a Promising Option for the Treatment of Antibiotic-Resistant Helicobacter pylori

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 658 ◽  
Author(s):  
Paweł Krzyżek ◽  
Emil Paluch ◽  
Grażyna Gościniak
Keyword(s):  
Helicobacter Pylori ◽  
Antimicrobial Properties ◽  
Multidrug Resistant ◽  
Future Application ◽  
Gastric Diseases ◽  
Antibiotic Resistant ◽  
Minimal Inhibitory Concentrations ◽  
Current Review ◽  
H Pylori

Helicobacter pylori is a Gram-negative bacterium responsible for the development of gastric diseases. The issue of spreading antibiotic resistance of H. pylori and its limited therapeutic options is an important topic in modern gastroenterology. This phenomenon is greatly associated with a very narrow range of antibiotics used in standard therapies and, as a consequence, an alarmingly high detection of multidrug-resistant H. pylori strains. For this reason, scientists are increasingly focused on the search for new substances that will not only exhibit antibacterial effect against H. pylori, but also potentiate the activity of antibiotics. The aim of the current review is to present scientific reports showing newly discovered or repurposed compounds with an ability to enhance the antimicrobial activity of classically used antibiotics against H. pylori. To gain a broader context in their future application in therapies of H. pylori infections, their antimicrobial properties, such as minimal inhibitory concentrations and minimal bactericidal concentrations, dose- and time-dependent mode of action, and, if characterized, anti-biofilm and/or in vivo activity are further described. The authors of this review hope that this article will encourage the scientific community to expand research on the important issue of synergistic therapies in the context of combating H. pylori infections.

scholarly journals Pse-T2, an Antimicrobial Peptide with High-Level, Broad-Spectrum Antimicrobial Potency and Skin Biocompatibility against Multidrug-ResistantPseudomonas aeruginosaInfection

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Hee Kyoung Kang ◽  
Chang Ho Seo ◽  
Tudor Luchian ◽  
Yoonkyung Park
Keyword(s):  
Antimicrobial Peptide ◽  
Membrane Integrity ◽  
Helical Structure ◽  
Multidrug Resistant ◽  
Bacterial Cells ◽  
Bacterial Strains ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Bacterial Membranes

ABSTRACTPseudin-2, isolated from the frogPseudis paradoxa, exhibits potent antibacterial activity but also cytotoxicity. In an effort to develop clinically applicable antimicrobial peptides (AMPs), we designed pseudin-2 analogs with Lys substitutions, resulting in elevated amphipathic α-helical structure and cationicity. In addition, truncated analogs of pseudin-2 and Lys-substituted peptides were synthesized to produce linear 18-residue amphipathic α-helices, which were further investigated for their mechanism and functions. These truncated analogs exhibited higher antimicrobial activity and lower cytotoxicity than pseudin-2. In particular, Pse-T2 showed marked pore formation, permeabilization of the outer/inner bacterial membranes, and DNA binding. Fluorescence spectroscopy and scanning electron microscopy showed that Pse-T2 kills bacterial cells by disrupting membrane integrity.In vivo, wounds infected with multidrug-resistant (MDR)Pseudomonas aeruginosahealed significantly faster when treated with Pse-T2 than did untreated wounds or wounds treated with ciprofloxacin. Moreover, Pse-T2 facilitated infected-wound closure by reducing inflammation through suppression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α). These data suggest that the small antimicrobial peptide Pse-T2 could be useful for future development of therapeutic agents effective against MDR bacterial strains.

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 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.

Sign in / Sign up

Export Citation Format

Share Document