scholarly journals Influence of the papiliocin peptide derived from Papilio xuthus on the perturbation of fungal cell membranes

2010 ◽  
Vol 311 (1) ◽  
pp. 70-75 ◽  
Author(s):  
Juneyoung Lee ◽  
Jae-Sam Hwang ◽  
Bomi Hwang ◽  
Jin-Kyoung Kim ◽  
Seong Ryul Kim ◽  
...  
2020 ◽  
Vol 17 (7) ◽  
pp. 918-928
Author(s):  
Sweta Sharma ◽  
Arpita Yadav

Background: : Currently, clinically used drugs for internal fungal infections have severe side effects. Patients suffering from severe fungal infections and those at a constant risk of developing such infections require long-term administration of safe antifungals. Objective: : This work deals with the design and development of safe, non-toxic antifungals derived from natural compounds for immune-compromised patients, such as HIV patients, who are at a constant risk of developing internal fungal infections. Methods: : Molecular modeling, docking and molecular dynamics simulation studies were performed on the main constituents of ginger and their derivatives to study their capability to inhibit 14α- demethylase enzyme. Results: : Ergosterol is the key component of the fungal cell membrane for its integrity and rigidity, synthesized from lanosterol catalyzed by 14α-demethylase enzyme. In our studies, it is determined that 6-gingerol, 6-paradol, 6-shogaol and their imidazole and triazole derivatives can inhibit the synthesis of ergosterol thus weakening the fungal cell membranes. The triazole derivative of 6-gingerol forms enhanced binding interactions with the active site residues of 14α-demethylase, carries an affinity for catalytically required cofactor heme and forms a stable complex with time without the probability of premature expulsion. Thus, this compound inhibits the formation of ergosterol leading to weakened fungal cell membranes and eventually death of fungal cells. Conclusion: : The triazole derivative of 6-gingerol is recommended as a lead compound for the development of non-toxic antifungals.


2017 ◽  
Vol 68 (01) ◽  
pp. 54-57
Author(s):  
Peneș Ovidiu N. ◽  
Neagu Andrei Mihai ◽  
Plața Flavius ◽  
Păun Silviu Dumitru

Silver has an intriguing, long history used for its antibiotic properties in human health care. It has been used in water purification, wound care, bone prostheses, reconstructive orthopaedic surgery, cardiac devices, catheters and surgical appliances, dressings and textiles. Advancing biotechnology has enabled incorporation of ionizable silver into fabrics, textiles and dressings for clinical use to reduce the risk of nosocomial infections and for personal hygiene. The antimicrobial action of silver is proportional to the bioactive silver ion (Ag(+)) released and its availability to interact with bacterial or fungal cell membranes. Silver metal and inorganic silver compounds ionize in the presence of water, body fluids or tissue exudates. The silver ion is biologically active and interacts with proteins, amino acid residues, free anions and receptors on mammalian and eukaryotic cell membranes. Bacterial sensitivity to silver is genetically determined and relates to the levels of intracellular silver uptake and its ability to interact and irreversibly denature key enzyme systems. Silver exhibits low toxicity in the human body. Minimal risk is expected due to clinical exposure by inhalation, ingestion, dermal application or through the urological or haematogenous route. Chronic ingestion or inhalation of silver preparations (especially colloidal silver) can lead to deposition of silver metal/silver sulphide particles in the skin (argyria), eye (argyrosis) and other organs. These are not life-threatening conditions but cosmetically undesirable. Silver is absorbed into the human body and enters the systemic circulation as a protein complex to be eliminated by the liver and kidneys. This complex mitigates the cellular toxicity of silver and contributes to tissue repair. Silver allergy is a known contraindication for using silver in medical devices or antibiotic textiles.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anastasiia A. Zakharova ◽  
Svetlana S. Efimova ◽  
Valery V. Malev ◽  
Olga S. Ostroumova

Abstract The one-sided addition of fengycin (FE) to planar lipid bilayers mimicking target fungal cell membranes up to 0.1 to 0.5 μM in the membrane bathing solution leads to the formation of well-defined and well-reproducible single-ion channels of various conductances in the picosiemens range. FE channels were characterized by asymmetric conductance-voltage characteristic. Membranes treated with FE showed nonideal cationic selectivity in potassium chloride bathing solutions. The membrane conductance induced by FE increased with the second power of the lipopeptide aqueous concentration, suggesting that at least FE dimers are involved in the formation of conductive subunits. The pore formation ability of FE was not distinctly affected by the molecular shape of membrane lipids but strongly depended on the presence of negatively charged species in the bilayer. FE channels were characterized by weakly pronounced voltage gating. Small molecules known to modify the transmembrane distribution of electrical potential and the lateral pressure profile were used to modulate the channel-forming activity of FE. The observed effects of membrane modifiers were attributed to changes in lipid packing and lipopeptide oligomerization in the membrane.


Author(s):  
Ergüden Bengü

Although there are innovations in the treatment of diseases caused by fungi and medicines with multiple targets have been developed, the search for a drug with a broad spectrum and without any side effects continues to date. It is generally accepted that determining the cellular target responsible for the toxic effect opens up new possibilities for the development of new drugs. Especially the effects of antifungal agents on the surface components of the fungal cell, on cell wall synthesis and the identification of the target site are crucial in antifungal drug development. Thus studies on the fungal cell membranes in connection with the antifungal agents, aim to develop new strategies for the therapy of fungal infections. Antifungal agents targeting fungal cell wall and cell membrane components have increased in importance in clinical studies. In this study, understanding the mechanism of action of benzyl alcohol, a known membrane fluidizer, and the determination of its cellular targets are aimed. We have shown that in the presence of sorbitol, the osmotic stabilizer, benzyl alcohol becomes less effective against yeast cell. Moreover, benzyl alcohol disrupts cell membrane, causing leakage of ions to the extracellular medium. Nuclear membrane is distorted upon treatment of yeast cells with benzyl alcohol. Thus, we conclude that both outer and inner yeast cell membranes are compromised by the action of benzyl alcohol.


2021 ◽  
Author(s):  
Sandeep Chakraborty

The “black fungus” (mucormycosis) epidemic in India in April-May 2021 [1] has exacerbated the Covid19 problem, and has been ascribed to over-usage of immuno-suppressive drugs (steroids) and uncontrolled diabetes [2]. This however does not answer the whole question, since these steroids are regularly prescribed for many diseases like RA, and even in the previous year (2020) in India for Covid19 patients.So what changed?Another (troubling) feature of the 2021 Covid19 wave in India has been the requirement (and often un- fortunately lack) of supportive oxygen. However, hypoxia (lack of oxygen) is a double-edged sword during pathogenesis [3], as hypoxia at infection sites creates a stressful environment for many host and pathogens. It has been realized that ‘manipulation of oxygen levels and/or oxygen-mediated signaling pathways in vivo may have both positive and negative effects on the outcome of’ fungal infections [4]. For example, Mucor irregularis has ways to circumvent the hypoxic environment, and thrives in skin where oxygen is minimal [5].The treatment Amphotericin provides the link - Ergosterol‘Amphotericin primarily kills yeast by simply binding ergosterol’ [6]. Ergosterol is an essential component of cell membranes of fungi and protozoa, analogous to cholesterol in animal cells [7]. Ergosterol biosynthesis requires oxygen [8]. And in low oxygen, cells that cannot make ergosterol absorb it from the external culture environment [9]. When oxygen is in abundance, cells use ergosterol which they biosynthesize [9].More feedback?‘Ergosterol, which is structurally analogous to cholesterol, has been used as a precursor of vitamin D2 and steroid hormone drugs’ [10].Why not other fungi?Oxygen level of the environment modulates the several genes of Mucor [11], while transcriptional profiling showed that the lipid metabolism was more active under hypoxia [12]. Maybe other fungi are not that adapt in reverting back to an aerobic environment, like Mucor. The evolution of sterols as an adaptive response to the rise of terrestrial oxygen has been proposed [13]. Is is possible the Mucor has best retained this primitive response to oxygen stress?


Nanoscale ◽  
2021 ◽  
Author(s):  
Joanna Zielińska ◽  
Milosz Wieczor ◽  
Paweł Chodnicki ◽  
Ewa Grela ◽  
Rafal Luchowski ◽  
...  

Amphotericin B (AmB), one of the most powerful but also toxic drugs used to treat systemic mycoses, is believed to selectively permeabilize fungal cell membranes to ions in a sterol-dependent...


Author(s):  
A. Tonosaki ◽  
M. Yamasaki ◽  
H. Washioka ◽  
J. Mizoguchi

A vertebrate disk membrane is composed of 40 % lipids and 60 % proteins. Its fracture faces have been classed into the plasmic (PF) and exoplasmic faces (EF), complementary with each other, like those of most other types of cell membranes. The hypothesis assuming the PF particles as representing membrane-associated proteins has been challenged by serious questions if they in fact emerge from the crystalline formation or decoration effects during freezing and shadowing processes. This problem seems to be yet unanswered, despite the remarkable case of the purple membrane of Halobacterium, partly because most observations have been made on the replicas from a single face of specimen, and partly because, in the case of photoreceptor membranes, the conformation of a rhodopsin and its relatives remains yet uncertain. The former defect seems to be partially fulfilled with complementary replica methods.


Author(s):  
R.J. Barrnett

This subject, is like observing the panorama of a mountain range, magnificent towering peaks, but it doesn't take much duration of observation to recognize that they are still in the process of formation. The mountains consist of approaches, materials and methods and the rocky substance of information has accumulated to such a degree that I find myself concentrating on the foothills in the foreground in order to keep up with the advance; the edifices behind form a wonderous, substantive background. It's a short history for such an accumulation and much of it has been moved by the members of the societies that make up this International Federation. My panel of speakers are here to provide what we hope is an interesting scientific fare, based on the fact that there is a continuum of biological organization from biochemical molecules through macromolecular assemblies and cellular membranes to the cell itself. Indeed, this fact explains the whole range of towering peaks that have emerged progressively during the past 25 years.


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