scholarly journals Insights into the Mode of Action of Chitosan as an Antibacterial Compound

2008 ◽  
Vol 74 (12) ◽  
pp. 3764-3773 ◽  
Author(s):  
Dina Raafat ◽  
Kristine von Bargen ◽  
Albert Haas ◽  
Hans-Georg Sahl
Keyword(s):  
Antimicrobial Activity ◽  
Cell Wall ◽  
Cell Membrane ◽  
Mode Of Action ◽  
Membrane Lipids ◽  
Expression Profiles ◽  
Transcriptional Response ◽  
Response Analysis ◽  
Sequence Of Events ◽  
Wide Range

ABSTRACT Chitosan is a polysaccharide biopolymer that combines a unique set of versatile physicochemical and biological characteristics which allow for a wide range of applications. Although its antimicrobial activity is well documented, its mode of action has hitherto remained only vaguely defined. In this work we investigated the antimicrobial mode of action of chitosan using a combination of approaches, including in vitro assays, killing kinetics, cellular leakage measurements, membrane potential estimations, and electron microscopy, in addition to transcriptional response analysis. Chitosan, whose antimicrobial activity was influenced by several factors, exhibited a dose-dependent growth-inhibitory effect. A simultaneous permeabilization of the cell membrane to small cellular components, coupled to a significant membrane depolarization, was detected. A concomitant interference with cell wall biosynthesis was not observed. Chitosan treatment of Staphylococcus simulans 22 cells did not give rise to cell wall lysis; the cell membrane also remained intact. Analysis of transcriptional response data revealed that chitosan treatment leads to multiple changes in the expression profiles of Staphylococcus aureus SG511 genes involved in the regulation of stress and autolysis, as well as genes associated with energy metabolism. Finally, a possible mechanism for chitosan's activity is postulated. Although we contend that there might not be a single classical target that would explain chitosan's antimicrobial action, we speculate that binding of chitosan to teichoic acids, coupled with a potential extraction of membrane lipids (predominantly lipoteichoic acid) results in a sequence of events, ultimately leading to bacterial death.

scholarly journals The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans

2021 ◽  
Author(s):  
Anna Biernasiuk ◽  
Anna Berecka-Rycerz ◽  
Anna Gumieniczek ◽  
Maria Malm ◽  
Krzysztof Z. Łączkowski ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Cell Membrane ◽  
Mode Of Action ◽  
Thiazole Derivatives ◽  
Fungal Cell ◽  
Erythrocyte Lysis ◽  
Low Cytotoxicity ◽  
High Antifungal Activity

Abstract Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly synthesized thiazole derivatives containing the cyclopropane system, showing promising activity against Candida spp., has been further investigated. We decided to verify their antifungal activity towards clinical Candida albicans isolated from the oral cavity of patients with hematological malignancies and investigate the mode of action on fungal cell, the effect of combination with the selected antimycotics, toxicity to erythrocytes, and lipophilicity. These studies were performed by the broth microdilution method, test with sorbitol and ergosterol, checkerboard technique, erythrocyte lysis assay, and reversed phase thin-layer chromatography, respectively. All derivatives showed very strong activity (similar and even higher than nystatin) against all C. albicans isolates with minimal inhibitory concentration (MIC) = 0.008–7.81 µg/mL Their mechanism of action may be related to action within the fungal cell wall structure and/or within the cell membrane. The interactions between the derivatives and the selected antimycotics (nystatin, chlorhexidine, and thymol) showed additive effect only in the case of combination some of them and thymol. The erythrocyte lysis assay confirmed the low cytotoxicity of these compounds as compared to nystatin. The high lipophilicity of the derivatives was related with their high antifungal activity. The present studies confirm that the studied thiazole derivatives containing the cyclopropane system appear to be a very promising group of compounds in treatment of infections caused by C. albicans. However, this requires further studies in vivo. Key points • The newly thiazoles showed high antifungal activity and some of them — additive effect in combination with thymol. • Their mode of action may be related with the influence on the structure of the fungal cell wall and/or the cell membrane. • The low cytotoxicity against erythrocytes and high lipophilicity of these derivatives are their additional good properties. Graphical abstract

scholarly journals Dramatic performance ofClostridium thermocellumexplained by its wide range of cellulase modalities

2016 ◽  
Vol 2 (2) ◽  
pp. e1501254 ◽  
Author(s):  
Qi Xu ◽  
Michael G. Resch ◽  
Kara Podkaminer ◽  
Shihui Yang ◽  
John O. Baker ◽  
...  
Keyword(s):  
Cell Wall ◽  
Bacterial Cell ◽  
Mode Of Action ◽  
Protein Complexes ◽  
Cellulose Degradation ◽  
Bacterial Cell Wall ◽  
Cellular Functions ◽  
Gene Deletions ◽  
Wide Range ◽  
Biomass Particles

Clostridium thermocellumis the most efficient microorganism for solubilizing lignocellulosic biomass known to date. Its high cellulose digestion capability is attributed to efficient cellulases consisting of both a free-enzyme system and a tethered cellulosomal system wherein carbohydrate active enzymes (CAZymes) are organized by primary and secondary scaffoldin proteins to generate large protein complexes attached to the bacterial cell wall. This study demonstrates thatC. thermocellumalso uses a type of cellulosomal system not bound to the bacterial cell wall, called the “cell-free” cellulosomal system. The cell-free cellulosome complex can be seen as a “long range cellulosome” because it can diffuse away from the cell and degrade polysaccharide substrates remotely from the bacterial cell. The contribution of these two types of cellulosomal systems inC. thermocellumwas elucidated by characterization of mutants with different combinations of scaffoldin gene deletions. The primary scaffoldin, CipA, was found to play the most important role in cellulose degradation byC. thermocellum, whereas the secondary scaffoldins have less important roles. Additionally, the distinct and efficient mode of action of theC. thermocellumexoproteome, wherein the cellulosomes splay or divide biomass particles, changes when either the primary or secondary scaffolds are removed, showing that the intact wild-type cellulosomal system is necessary for this essential mode of action. This new transcriptional and proteomic evidence shows that a functional primary scaffoldin plays a more important role compared to secondary scaffoldins in the proper regulation of CAZyme genes, cellodextrin transport, and other cellular functions.

scholarly journals Influence of Ca2+ Ions on the Activity of Lantibiotics Containing a Mersacidin-Like Lipid II Binding Motif

2009 ◽  
Vol 75 (13) ◽  
pp. 4427-4434 ◽  
Author(s):  
T. Böttiger ◽  
T. Schneider ◽  
B. Martínez ◽  
H.-G. Sahl ◽  
I. Wiedemann
Keyword(s):  
Antimicrobial Activity ◽  
Cell Wall ◽  
Mode Of Action ◽  
Cell Wall Biosynthesis ◽  
Binding Motif ◽  
Bacterial Membrane ◽  
Lipid Ii ◽  
Lacticin 3147 ◽  
Lacticin 481

ABSTRACT Mersacidin binds to lipid II and thus blocks the transglycosylation step of the cell wall biosynthesis. Binding of lipid II involves a special motif, the so-called mersacidin-lipid II binding motif, which is conserved in a major subgroup of lantibiotics. We analyzed the role of Ca2+ ions in the mode of action of mersacidin and some related peptides containing a mersacidin-like lipid II binding motif. We found that the stimulating effect of Ca2+ ions on the antimicrobial activity known for mersacidin also applies to plantaricin C and lacticin 3147. Ca2+ ions appear to facilitate the interaction of the lantibiotics with the bacterial membrane and with lipid II rather than being an essential part of a peptide-lipid II complex. In the case of lacticin 481, both the interaction with lipid II and the antimicrobial activity were Ca2+ independent.

scholarly journals Mechanisms of Non-Vesicular Exchange of Lipids at Membrane Contact Sites: Of Shuttles, Tunnels and, Funnels

2021 ◽  
Vol 9 ◽  
Author(s):  
Pascal F. Egea
Keyword(s):  
Cell Membrane ◽  
Cell Biology ◽  
Membrane Lipids ◽  
Atp Synthesis ◽  
Vesicular Trafficking ◽  
Lipid Transfer ◽  
Organelle Biogenesis ◽  
Membrane Contact Sites ◽  
Wide Range ◽  
Membrane Bound

Eukaryotic cells are characterized by their exquisite compartmentalization resulting from a cornucopia of membrane-bound organelles. Each of these compartments hosts a flurry of biochemical reactions and supports biological functions such as genome storage, membrane protein and lipid biosynthesis/degradation and ATP synthesis, all essential to cellular life. Acting as hubs for the transfer of matter and signals between organelles and throughout the cell, membrane contacts sites (MCSs), sites of close apposition between membranes from different organelles, are essential to cellular homeostasis. One of the now well-acknowledged function of MCSs involves the non-vesicular trafficking of lipids; its characterization answered one long-standing question of eukaryotic cell biology revealing how some organelles receive and distribute their membrane lipids in absence of vesicular trafficking. The endoplasmic reticulum (ER) in synergy with the mitochondria, stands as the nexus for the biosynthesis and distribution of phospholipids (PLs) throughout the cell by contacting nearly all other organelle types. MCSs create and maintain lipid fluxes and gradients essential to the functional asymmetry and polarity of biological membranes throughout the cell. Membrane apposition is mediated by proteinaceous tethers some of which function as lipid transfer proteins (LTPs). We summarize here the current state of mechanistic knowledge of some of the major classes of LTPs and tethers based on the available atomic to near-atomic resolution structures of several “model” MCSs from yeast but also in Metazoans; we describe different models of lipid transfer at MCSs and analyze the determinants of their specificity and directionality. Each of these systems illustrate fundamental principles and mechanisms for the non-vesicular exchange of lipids between eukaryotic membrane-bound organelles essential to a wide range of cellular processes such as at PL biosynthesis and distribution, lipid storage, autophagy and organelle biogenesis.

Secretion and export of amylolytic activities in Schwanniomyces alluvius

1985 ◽  
Vol 63 (5) ◽  
pp. 366-371 ◽  
Author(s):  
C. V. Lusena ◽  
C. C. Champagne ◽  
G. B. Calleja
Keyword(s):  
Cell Wall ◽  
Sodium Dodecyl Sulfate ◽  
Cell Membrane ◽  
Molecular Species ◽  
Gel Electrophoresis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Periplasmic Space ◽  
Whole Cells ◽  
Sequence Of Events

We define secretion as the passage from the cytoplasm, across the cell membrane, to the periplasmic space. By contrast, export is the passage across the cell wall into the medium. Operationally we distinguish the two processes by comparing the molecular species in the medium, in whole cells, and in spheroplasts. Two techniques make the task possible: complete spheroplast preparation and detection of activities in bands obtained by sodium dodecyl sulfate – polyacrylamide gel electrophoresis. The capability of Schwanniomyces alluvius to export α-amylase during stationary phase gradually increased with continual successive transfers from a slant culture to a liquid medium containing starch until a maximum was reached. Only cells which had developed full capability to export α-amylase were used in these studies. About 1 h after the end of the log phase of growth, α-amylase and glucoamylase start to be exported above constitutive levels and a concentration 10 times the constitutive level is reached 3 h later. Electrophoretic results show that at least three active molecular species of α-amylase appear in the cytoplasm at the end of log phase and that the smaller component (52 000 daltons) is secreted into the periplasm 0.5 h later and starts to be exported 1 h after that. The sequence of events suggests that the larger species are precursors of the 52 000 dalton molecules. Amylolytic activities in the cytoplasm and periplasm in late log phase are not detectable.

The role of blood cell membrane lipids on the mode of action of HIV-1 fusion inhibitor sifuvirtide

2010 ◽  
Vol 403 (3-4) ◽  
pp. 270-274 ◽  
Author(s):  
Pedro M. Matos ◽  
Teresa Freitas ◽  
Miguel A.R.B. Castanho ◽  
Nuno C. Santos
Keyword(s):  
Cell Membrane ◽  
Blood Cell ◽  
Mode Of Action ◽  
Membrane Lipids ◽  
Fusion Inhibitor ◽  
Hiv 1

scholarly journals The Viscoelastic Properties of the Fungal Cell Wall Allow Traffic of AmBisome as Intact Liposome Vesicles

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Louise Walker ◽  
Prashant Sood ◽  
Megan D. Lenardon ◽  
Gillian Milne ◽  
Jon Olson ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Cell Membrane ◽  
Amphotericin B ◽  
Mode Of Action ◽  
Viscoelastic Properties ◽  
Fungal Cell Wall ◽  
Fungal Cell ◽  
Pass Through ◽  
Cell Wall Porosity

ABSTRACT The fungal cell wall is a critically important structure that represents a permeability barrier and protective shield. We probed Candida albicans and Cryptococcus neoformans with liposomes containing amphotericin B (AmBisome), with or without 15-nm colloidal gold particles. The liposomes have a diameter of 60 to 80 nm, and yet their mode of action requires them to penetrate the fungal cell wall to deliver amphotericin B to the cell membrane, where it binds to ergosterol. Surprisingly, using cryofixation techniques with electron microscopy, we observed that the liposomes remained intact during transit through the cell wall of both yeast species, even though the predicted porosity of the cell wall (pore size, ~5.8 nm) is theoretically too small to allow these liposomes to pass through intact. C. albicans mutants with altered cell wall thickness and composition were similar in both their in vitro AmBisome susceptibility and the ability of liposomes to penetrate the cell wall. AmBisome exposed to ergosterol-deficient C. albicans failed to penetrate beyond the mannoprotein-rich outer cell wall layer. Melanization of C. neoformans and the absence of amphotericin B in the liposomes were also associated with a significant reduction in liposome penetration. Therefore, AmBisome can reach cell membranes intact, implying that fungal cell wall viscoelastic properties are permissive to vesicular structures. The fact that AmBisome can transit through chemically diverse cell wall matrices when these liposomes are larger than the theoretical cell wall porosity suggests that the wall is capable of rapid remodeling, which may also be the mechanism for release of extracellular vesicles. IMPORTANCE AmBisome is a broad-spectrum fungicidal antifungal agent in which the hydrophobic polyene antibiotic amphotericin B is packaged within a 60- to 80-nm liposome. The mode of action involves perturbation of the fungal cell membrane by selectively binding to ergosterol, thereby disrupting membrane function. We report that the AmBisome liposome transits through the cell walls of both Candida albicans and Cryptococcus neoformans intact, despite the fact that the liposome is larger than the theoretical cell wall porosity. This implies that the cell wall has deformable, viscoelastic properties that are permissive to transwall vesicular traffic. These observations help explain the low toxicity of AmBisome, which can deliver its payload directly to the cell membrane without unloading the polyene in the cell wall. In addition, these findings suggest that extracellular vesicles may also be able to pass through the cell wall to deliver soluble and membrane-bound effectors and other molecules to the extracellular space.

scholarly journals Antimicrobial activity and mode of action of 1,8-cineol against carbapenemase-producing Klebsiella pneumoniae

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chew-Li Moo ◽  
Mohd Azuraidi Osman ◽  
Shun-Kai Yang ◽  
Wai-Sum Yap ◽  
Saila Ismail ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antimicrobial Activity ◽  
Cell Membrane ◽  
Klebsiella Pneumoniae ◽  
Ethidium Bromide ◽  
Bacterial Cell ◽  
Mode Of Action ◽  
Membrane Damage ◽  
Electron Microscopies ◽  
Bacterial Cell Membrane

AbstractAntimicrobial resistance remains one of the most challenging issues that threatens the health of people around the world. Plant-derived natural compounds have received considerable attention for their potential role to mitigate antibiotic resistance. This study was carried out to assess the antimicrobial activity and mode of action of a monoterpene, 1,8-cineol (CN) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Results showed that resazurin microplate assay and time-kill analysis revealed bactericidal effects of CN at 28.83 mg/mL. Zeta potential showed that CN increased the surface charge of bacteria and an increase of outer membrane permeability was also detected. CN was able to cause leakage of proteins and nucleic acids in KPC-KP cells upon exposure to CN and ethidium bromide influx/efflux experiment showed the uptake of ethidium bromide into the cell; this was attributed to membrane damage. CN was also found to induce oxidative stress in CN-treated KPC-KP cells through generation of reactive oxygen species which initiated lipid peroxidation and thus damaging the bacterial cell membrane. Scanning and transmission electron microscopies further confirmed the disruption of bacterial cell membrane and loss of intracellular materials. In this study, we demonstrated that CN induced oxidative stress and membrane damage resulting in KPC-KP cell death.

Chemical diversity and mode of action of natural products targeting lipids in the eukaryotic cell membrane

2020 ◽  
Vol 37 (5) ◽  
pp. 677-702 ◽  
Author(s):  
Shinichi Nishimura ◽  
Nobuaki Matsumori
Keyword(s):  
Natural Products ◽  
Cell Membrane ◽  
Mode Of Action ◽  
Membrane Lipids ◽  
Eukaryotic Cell ◽  
Review Article ◽  
Chemical Diversity ◽  
Research Tools

This review article focuses on natural products that bind to eukaryotic membrane lipids, and includes clinically important molecules and key research tools. How their mechanism was unveiled, and how they are used in research are also mentioned.

scholarly journals Satureja montana L. and Origanum majorana L. Decoctions: Antimicrobial Activity, Mode of Action and Phenolic Characterization

Antibiotics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 294 ◽  
Author(s):  
Fernanda Gomes ◽  
Maria Inês Dias ◽  
Ângela Lima ◽  
Lillian Barros ◽  
Maria Elisa Rodrigues ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Cell Membrane ◽  
Membrane Integrity ◽  
Medicinal And Aromatic Plants ◽  
Candida Spp ◽  
Gram Positive ◽  
Gram Negative ◽  
Wide Range ◽  
Origanum Majorana ◽  
Satureja Montana

Medicinal and aromatic plants are known to have a wide range of uses and health benefits, and should be exploited for their bioactivity. Here we evaluated the antimicrobial activity of decoctions of Satureja montana L. and Origanum majorana L. against Gram-positive and Gram-negative bacteria and Candida spp. as well as their mechanism of action and phenolic characterization. The Satureja montana and Origanum majorana extracts were effective against a broad set of species, including the Gram-positive Staphylococcus aureus, Enterococcus faecalis, and Streptococcus dysgalactiae and the Gram-negative Klebsiella pneumoniae and Pseudomonas aeruginosa. Both extracts were found to have rosmarinic acid as the main phenolic compound and to exert their antimicrobial activity at the level of the cell membrane. Membrane perturbations by the extracts impaired cell membrane integrity only a few hours after exposure. This study confirms the bioactive potential of Satureja montana and Origanum majorana decoctions, and supports the development of novel formulations with wide antimicrobial properties based on these medicinal and aromatic herbs.

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