scholarly journals Bactericidal Properties of Rod-, Peanut-, and Star-Shaped Gold Nanoparticles Coated with Ceragenin CSA-131 against Multidrug-Resistant Bacterial Strains

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 425
Author(s):  
Sylwia Joanna Chmielewska ◽  
Karol Skłodowski ◽  
Joanna Depciuch ◽  
Piotr Deptuła ◽  
Ewelina Piktel ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Bactericidal Activity ◽  
Molecular Mechanisms ◽  
Covalent Bond ◽  
Multidrug Resistant ◽  
Host Cells ◽  
Cooh Group ◽  
Bacterial Strains ◽  
Au Nps ◽  
Bacterial Membranes

Background: The ever-growing number of infections caused by multidrug-resistant (MDR) bacterial strains requires an increased effort to develop new antibiotics. Herein, we demonstrate that a new class of gold nanoparticles (Au NPs), defined by shape and conjugated with ceragenin CSA-131 (cationic steroid antimicrobial), display strong bactericidal activity against intractable superbugs. Methods: For the purpose of research, we developed nanosystems with rod- (AuR NPs@CSA-131), peanut-(AuP NPs@CSA-131) and star-shaped (AuS NPs@CSA-131) metal cores. Those nanosystems were evaluated against bacterial strains representing various groups of MDR (multidrug-resistant) Gram-positive (MRSA, MRSE, and MLSb) and Gram-negative (ESBL, AmpC, and CR) pathogens. Assessment of MICs (minimum inhibitory concentrations)/MBCs (minimum bactericidal concentrations) and killing assays were performed as a measure of their antibacterial activity. In addition to a comprehensive analysis of bacterial responses involving the generation of ROS (reactive oxygen species), plasma membrane permeabilization and depolarization, as well as the release of protein content, were performed to investigate the molecular mechanisms of action of the nanosystems. Finally, their hemocompatibility was assessed by a hemolysis assay. Results: All of the tested nanosystems exerted potent bactericidal activity in a manner resulting in the generation of ROS, followed by damage of the bacterial membranes and the leakage of intracellular content. Notably, the killing action occurred with all of the bacterial strains evaluated, including those known to be drug resistant, and at concentrations that did not impact the growth of host cells. Conclusions: Conjugation of CSA-131 with Au NPs by covalent bond between the COOH group from MHDA and NH3 from CSA-131 potentiates the antimicrobial activity of this ceragenin if compared to its action alone. Results validate the development of AuR NPs@CSA-131, AuP NPs@CSA-131, and AuS NPs@CSA-131 as potential novel nanoantibiotics that might effectively eradicate MDR bacteria.

scholarly journals In Vitro Bactericidal Activity of Human β-Defensin 3 against Multidrug-Resistant Nosocomial Strains

2006 ◽  
Vol 50 (2) ◽  
pp. 806-809 ◽  
Author(s):  
Giuseppantonio Maisetta ◽  
Giovanna Batoni ◽  
Semih Esin ◽  
Walter Florio ◽  
Daria Bottai ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Bactericidal Activity ◽  
Stenotrophomonas Maltophilia ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Gram Negative

ABSTRACT The antimicrobial activity of human β-defensin 3 (hBD-3) against multidrug-resistant clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii was evaluated. A fast bactericidal effect (within 20 min) against all bacterial strains tested was observed. The presence of 20% human serum abolished the bactericidal activity of hBD-3 against gram-negative strains and reduced the activity of the peptide against gram-positive strains.

scholarly journals The Zeamine Antibiotics Affect the Integrity of Bacterial Membranes

2014 ◽  
Vol 81 (3) ◽  
pp. 1139-1146 ◽  
Author(s):  
Joleen Masschelein ◽  
Charlien Clauwers ◽  
Karen Stalmans ◽  
Koen Nuyts ◽  
Wim De Borggraeve ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Electrostatic Interactions ◽  
Direct Consequence ◽  
Time Lapse ◽  
Multidrug Resistant ◽  
Peptide Antibiotics ◽  
Serratia Plymuthica ◽  
Gram Negative ◽  
Content Type ◽  
Bacterial Membranes

ABSTRACTThe zeamines (zeamine, zeamine I, and zeamine II) constitute an unusual class of cationic polyamine-polyketide-nonribosomal peptide antibiotics produced bySerratia plymuthicaRVH1. They exhibit potent bactericidal activity, killing a broad range of Gram-negative and Gram-positive bacteria, including multidrug-resistant pathogens. Examination of their specific mode of action and molecular target revealed that the zeamines affect the integrity of cell membranes. The zeamines provoke rapid release of carboxyfluorescein from unilamellar vesicles with different phospholipid compositions, demonstrating that they can interact directly with the lipid bilayer in the absence of a specific target. DNA, RNA, fatty acid, and protein biosynthetic processes ceased simultaneously at subinhibitory levels of the antibiotics, presumably as a direct consequence of membrane disruption. The zeamine antibiotics also facilitated the uptake of small molecules, such as 1-N-phenylnaphtylamine, indicating their ability to permeabilize the Gram-negative outer membrane (OM). The valine-linked polyketide moiety present in zeamine and zeamine I was found to increase the efficiency of this process. In contrast, translocation of the large hydrophilic fluorescent peptidoglycan binding protein PBDKZ-GFP was not facilitated, suggesting that the zeamines cause subtle perturbation of the OM rather than drastic alterations or defined pore formation. At zeamine concentrations above those required for growth inhibition, membrane lysis occurred as indicated by time-lapse microscopy. Together, these findings show that the bactericidal activity of the zeamines derives from generalized membrane permeabilization, which likely is initiated by electrostatic interactions with negatively charged membrane components.

scholarly journals In VitroCytotoxic Effects of Gold Nanoparticles Coated with Functional Acyl Homoserine Lactone Lactonase Protein from Bacillus licheniformis and Their Antibiofilm Activity against Proteus Species

2014 ◽  
Vol 59 (2) ◽  
pp. 763-771 ◽  
Author(s):  
Gopalakrishnan Vinoj ◽  
Rashmirekha Pati ◽  
Avinash Sonawane ◽  
Baskaralingam Vaseeharan
Keyword(s):  
Gold Nanoparticles ◽  
Bacillus Licheniformis ◽  
Bacterial Colonization ◽  
Cell Surface Hydrophobicity ◽  
Homoserine Lactone ◽  
Surface Hydrophobicity ◽  
Multidrug Resistant ◽  
Host Cells ◽  
Antibiofilm Activity ◽  
Content Type

ABSTRACTN-acylated homoserine lactonases are known to inhibit the signaling molecules of the biofilm-forming pathogens. In this study, gold nanoparticles were coated with N-acylated homoserine lactonase proteins (AiiA AuNPs) purified fromBacillus licheniformis. The AiiA AuNPs were characterized by UV-visible spectra, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The synthesized AiiA AuNPs were found to be spherical in shape and 10 to 30 nm in size. Treatment with AiiA protein-coated AuNPs showed maximum reduction in exopolysaccharide production, metabolic activities, and cell surface hydrophobicity and potent antibiofilm activity against multidrug-resistantProteusspecies compared to treatment with AiiA protein alone. AiiA AuNPs exhibited potent antibiofilm activity at 2 to 8 μM concentrations without being harmful to the macrophages. We conclude that at a specific dose, AuNPs coated with AiiA can kill bacteria without harming the host cells, thus representing a potential template for the design of novel antibiofilm and antibacterial protein drugs to decrease bacterial colonization and to overcome the problem of drug resistance. In summary, our data suggest that the combined effect of the lactonase and the gold nanoparticles of the AiiA AuNPs has promising antibiofilm activity against biofilm-forming and multidrug-resistantProteusspecies.

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 Amphiphilic Aminoglycosides as Medicinal Agents

2020 ◽  
Vol 21 (19) ◽  
pp. 7411
Author(s):  
Clément Dezanet ◽  
Julie Kempf ◽  
Marie-Paule Mingeot-Leclercq ◽  
Jean-Luc Décout
Keyword(s):  
Nucleic Acids ◽  
Biological Effects ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Bacterial Membranes ◽  
Abasic Sites ◽  
Structure Activity ◽  
Antibiotic Drugs ◽  
Antibiotic Drug

The conjugation of hydrophobic group(s) to the polycationic hydrophilic core of the antibiotic drugs aminoglycosides (AGs), targeting ribosomal RNA, has led to the development of amphiphilic aminoglycosides (AAGs). These drugs exhibit numerous biological effects, including good antibacterial effects against susceptible and multidrug-resistant bacteria due to the targeting of bacterial membranes. In the first part of this review, we summarize our work in identifying and developing broad-spectrum antibacterial AAGs that constitute a new class of antibiotic agents acting on bacterial membranes. The target-shift strongly improves antibiotic activity against bacterial strains that are resistant to the parent AG drugs and to antibiotic drugs of other classes, and renders the emergence of resistant Pseudomonas aeruginosa strains highly difficult. Structure–activity and structure–eukaryotic cytotoxicity relationships, specificity and barriers that need to be crossed in their development as antibacterial agents are delineated, with a focus on their targets in membranes, lipopolysaccharides (LPS) and cardiolipin (CL), and the corresponding mode of action against Gram-negative bacteria. At the end of the first part, we summarize the other recent advances in the field of antibacterial AAGs, mainly published since 2016, with an emphasis on the emerging AAGs which are made of an AG core conjugated to an adjuvant or an antibiotic drug of another class (antibiotic hybrids). In the second part, we briefly illustrate other biological and biochemical effects of AAGs, i.e., their antifungal activity, their use as delivery vehicles of nucleic acids, of short peptide (polyamide) nucleic acids (PNAs) and of drugs, as well as their ability to cleave DNA at abasic sites and to inhibit the functioning of connexin hemichannels. Finally, we discuss some aspects of structure–activity relationships in order to explain and improve the target selectivity of AAGs.

Rod-shaped gold nanoparticles exert potent candidacidal activity and decrease the adhesion of fungal cells

Nanomedicine ◽  
2020 ◽  
Author(s):  
Ewelina Piktel ◽  
Łukasz Suprewicz ◽  
Joanna Depciuch ◽  
Mateusz Cieśluk ◽  
Sylwia Chmielewska ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Fungicidal Activity ◽  
Fungal Infections ◽  
Drug Susceptibility ◽  
Host Cells ◽  
Oxygen Species ◽  
Au Nps ◽  
Force Microscopy ◽  
Atomic Force ◽  
Colony Counting

Aim: To investigate the fungicidal activity of rod-shaped gold nanoparticles (AuR NPs) against Candida strains isolated from hematooncological patients and representative strains of filamentous fungi. Methods: Colony-counting assays, colorimetric and fluorometric methods and atomic force microscopy were employed. Results: AuR NPs were characterized by their potent fungicidal activity against all tested isolates, regardless of the species or drug susceptibility, at concentrations that are nontoxic to the host cells. The membrane-permeabilizing properties of AuR NPs and induction of reactive oxygen species were recognized as crucial for fungicidal activity. Conclusions: The results provide a rationale for the development of nonspherical Au NPs as effective antifungals or drug-delivery carriers to improve therapy for fungal infections.

Molecular mechanisms associated with quinolone resistance in Enterobacteriaceae: review and update

2020 ◽  
Vol 114 (10) ◽  
pp. 770-781 ◽  
Author(s):  
Robab Azargun ◽  
Pourya Gholizadeh ◽  
Vahid Sadeghi ◽  
Hasan Hosainzadegan ◽  
Vahideh Tarhriz ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Gene Mutations ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Drug Binding ◽  
Quinolone Resistance ◽  
New Drugs ◽  
Bacterial Strains ◽  
Active Efflux

Abstract Background Quinolones are broad-spectrum antibiotics, which are used for the treatment of different infectious diseases associated with Enterobacteriaceae. During recent decades, the wide use as well as overuse of quinolones against diverse infections has led to the emergence of quinolone-resistant bacterial strains. Herein, we present the development of quinolone antibiotics, their function and also the different quinolone resistance mechanisms in Enterobacteriaceae by reviewing recent literature. Methods All data were extracted from Google Scholar search engine and PubMed site, using keywords; quinolone resistance, Enterobacteriaceae, plasmid-mediated quinolone resistance, etc. Results and conclusion The acquisition of resistance to quinolones is a complex and multifactorial process. The main resistance mechanisms consist of one or a combination of target-site gene mutations altering the drug-binding affinity of target enzymes. Other mechanisms of quinolone resistance are overexpression of AcrAB-tolC multidrug-resistant efflux pumps and downexpression of porins as well as plasmid-encoded resistance proteins including Qnr protection proteins, aminoglycoside acetyltransferase (AAC(6′)-Ib-cr) and plasmid-encoded active efflux pumps such as OqxAB and QepA. The elucidation of resistance mechanisms will help researchers to explore new drugs against the resistant strains.

scholarly journals Antibacterial Activity of a Cationic Antimicrobial Peptide against Multidrug-Resistant Gram-Negative Clinical Isolates and Their Potential Molecular Targets

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5035
Author(s):  
Sandra Patricia Rivera-Sánchez ◽  
Helen Astrid Agudelo-Góngora ◽  
José Oñate-Garzón ◽  
Liliana Janeth Flórez-Elvira ◽  
Adriana Correa ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Genomic Dna ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Bacterial Strains ◽  
Scanning Calorimetry ◽  
Cationic Antimicrobial Peptide ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Membrane Models

Antimicrobial resistance reduces the efficacy of antibiotics. Infections caused by multidrug-resistant (MDR), Gram-negative bacterial strains, such as Klebsiella pneumoniae (MDRKp) and Pseudomonas aeruginosa (MDRPa), are a serious threat to global health. However, cationic antimicrobial peptides (CAMPs) are promising as an alternative therapeutic strategy against MDR strains. In this study, the inhibitory activity of a cationic peptide, derived from cecropin D-like (ΔM2), against MDRKp and MDRPa clinical isolates, and its interaction with membrane models and bacterial genomic DNA were evaluated. In vitro antibacterial activity was determined using the broth microdilution test, whereas interactions with lipids and DNA were studied by differential scanning calorimetry and electronic absorption, respectively. A strong bactericidal effect of ΔM2 against MDR strains, with minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) between 4 and 16 μg/mL, was observed. The peptide had a pronounced effect on the thermotropic behavior of the 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) membrane models that mimic bacterial membranes. Finally, the interaction between the peptide and genomic DNA (gDNA) showed a hyperchromic effect, which indicates that ΔM2 can denature bacterial DNA strands via the grooves.

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