Antimicrobial mode of action of secretions from the metapleural gland ofMytmecia gulosa(Australian bull ant)

1995 ◽  
Vol 41 (2) ◽  
pp. 136-144 ◽  
Author(s):  
J. A. Mackintosh ◽  
J. E. Trimble ◽  
A. J. Beattie ◽  
D. A. Veal ◽  
M. K. Jones ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antimicrobial Agents ◽  
Structural Integrity ◽  
Phospholipid Bilayer ◽  
Active Components ◽  
Cytoplasmic Matrix ◽  
Metapleural Glands ◽  
Total Leakage ◽  
Membrane Bound ◽  
And Function

Secretions from exocrine metapleural glands of Myrmecia gulosa (Australian bull ant) exhibit broad-spectrum antimicrobial activity. Treatment of the yeast Candida albicans with metapleural secretion resulted in the rapid and total leakage of K+ions from cells within 10 min. Ultrastructural analysis of the bacteria Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa, and cells and protoplasts of Candida albicans demonstrated gross damage of the cell membrane and aggregation of the cytoplasmic matrix of treated cells. Degradation of membrane-bound organelles was also observed in Candida albicans. The antimicrobially active components of metapleural secretions were nonpolar and interacted with the phospholipid bilayer, causing damage to the structural integrity of liposomes and the release of carboxyfluorescein. The data suggest that the antimicrobial agents in metapleural secretion act primarily by disrupting the structure and function of the phospholipid bilayer of the cytoplasmic membrane.Key words: ant metapleural secretion, antimicrobial, Candida albicans, cytoplasmic membrane.

Spatial control of actin-based motility through plasmalemmal PtdIns(4,5)P2-rich raft assemblies.

2005 ◽  
Vol 72 ◽  
pp. 119-127 ◽  
Author(s):  
Tamara Golub ◽  
Caroni Pico
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Actin Cytoskeleton ◽  
Lipid Rafts ◽  
Patch Clustering ◽  
Pkc Protein Kinase C ◽  
Membrane Bound ◽  
And Function ◽  
Cytoskeleton Dynamics ◽  
Syndrome Protein

The interactions of cells with their environment involve regulated actin-based motility at defined positions along the cell surface. Sphingolipid- and cholesterol-dependent microdomains (rafts) order proteins at biological membranes, and have been implicated in most signalling processes at the cell surface. Many membrane-bound components that regulate actin cytoskeleton dynamics and cell-surface motility associate with PtdIns(4,5)P2-rich lipid rafts. Although raft integrity is not required for substrate-directed cell spreading, or to initiate signalling for motility, it is a prerequisite for sustained and organized motility. Plasmalemmal rafts redistribute rapidly in response to signals, triggering motility. This process involves the removal of rafts from sites that are not interacting with the substrate, apparently through endocytosis, and a local accumulation at sites of integrin-mediated substrate interactions. PtdIns(4,5)P2-rich lipid rafts can assemble into patches in a process depending on PtdIns(4,5)P2, Cdc42 (cell-division control 42), N-WASP (neural Wiskott-Aldrich syndrome protein) and actin cytoskeleton dynamics. The raft patches are sites of signal-induced actin assembly, and their accumulation locally promotes sustained motility. The patches capture microtubules, which promote patch clustering through PKA (protein kinase A), to steer motility. Raft accumulation at the cell surface, and its coupling to motility are influenced greatly by the expression of intrinsic raft-associated components that associate with the cytosolic leaflet of lipid rafts. Among them, GAP43 (growth-associated protein 43)-like proteins interact with PtdIns(4,5)P2 in a Ca2+/calmodulin and PKC (protein kinase C)-regulated manner, and function as intrinsic determinants of motility and anatomical plasticity. Plasmalemmal PtdIns(4,5)P2-rich raft assemblies thus provide powerful organizational principles for tight spatial and temporal control of signalling in motility.

scholarly journals Codon harmonization reduces amino acid misincorporation in bacterially expressed P. falciparum proteins and improves their immunogenicity

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Neeraja Punde ◽  
Jennifer Kooken ◽  
Dagmar Leary ◽  
Patricia M. Legler ◽  
Evelina Angov
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Codon Usage ◽  
Dna Sequences ◽  
Structural Integrity ◽  
Host Cells ◽  
Loss Of Function ◽  
Species Specific ◽  
And Function ◽  
The Impact

Abstract Codon usage frequency influences protein structure and function. The frequency with which codons are used potentially impacts primary, secondary and tertiary protein structure. Poor expression, loss of function, insolubility, or truncation can result from species-specific differences in codon usage. “Codon harmonization” more closely aligns native codon usage frequencies with those of the expression host particularly within putative inter-domain segments where slower rates of translation may play a role in protein folding. Heterologous expression of Plasmodium falciparum genes in Escherichia coli has been a challenge due to their AT-rich codon bias and the highly repetitive DNA sequences. Here, codon harmonization was applied to the malarial antigen, CelTOS (Cell-traversal protein for ookinetes and sporozoites). CelTOS is a highly conserved P. falciparum protein involved in cellular traversal through mosquito and vertebrate host cells. It reversibly refolds after thermal denaturation making it a desirable malarial vaccine candidate. Protein expressed in E. coli from a codon harmonized sequence of P. falciparum CelTOS (CH-PfCelTOS) was compared with protein expressed from the native codon sequence (N-PfCelTOS) to assess the impact of codon usage on protein expression levels, solubility, yield, stability, structural integrity, recognition with CelTOS-specific mAbs and immunogenicity in mice. While the translated proteins were expected to be identical, the translated products produced from the codon-harmonized sequence differed in helical content and showed a smaller distribution of polypeptides in mass spectra indicating lower heterogeneity of the codon harmonized version and fewer amino acid misincorporations. Substitutions of hydrophobic-to-hydrophobic amino acid were observed more commonly than any other. CH-PfCelTOS induced significantly higher antibody levels compared with N-PfCelTOS; however, no significant differences in either IFN-γ or IL-4 cellular responses were detected between the two antigens.

scholarly journals Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alice C. Copsey ◽  
Mario R. O. Barsottini ◽  
Benjamin May ◽  
Fei Xu ◽  
Mary S. Albury ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Future Development ◽  
Therapeutic Target ◽  
Fungicide Resistance ◽  
Alternative Oxidase ◽  
Antifungal Agents ◽  
Candida Auris ◽  
Novel Treatments ◽  
Membrane Bound ◽  
Self Assembled

AbstractCandidemia caused by Candida spp. is a serious threat in hospital settings being a major cause of acquired infection and death and a possible contributor to Covid-19 mortality. Candidemia incidence has been rising worldwide following increases in fungicide-resistant pathogens highlighting the need for more effective antifungal agents with novel modes of action. The membrane-bound enzyme alternative oxidase (AOX) promotes fungicide resistance and is absent in humans making it a desirable therapeutic target. However, the lipophilic nature of the AOX substrate (ubiquinol-10) has hindered its kinetic characterisation in physiologically-relevant conditions. Here, we present the purification and expression of recombinant AOXs from C. albicans and C. auris in a self-assembled proteoliposome (PL) system. Kinetic parameters (Km and Vmax) with respect to ubiquinol-10 have been determined. The PL system has also been employed in dose–response assays with novel AOX inhibitors. Such information is critical for the future development of novel treatments for Candidemia.

scholarly journals Clinical Relevance of Elastin in the Structure and Function of Skin

2021 ◽  
Author(s):  
Leslie Baumann ◽  
Eric F Bernstein ◽  
Anthony S Weiss ◽  
Damien Bates ◽  
Shannon Humphrey ◽  
...  
Keyword(s):  
Wound Healing ◽  
Clinical Relevance ◽  
Structural Integrity ◽  
Elastic Fiber ◽  
Subcutaneous Fat ◽  
Structure And Function ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Superficial Dermis ◽  
And Function

Abstract Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin’s structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance. The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin’s appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network. This review describes the clinical relevance of elastin in the context of the structure and function of healthy and aging skin, wound healing, and scars and introduces new approaches being developed to target elastin production and elastic fiber formation.

scholarly journals Combined Supplementation of Choline and Docosahexaenoic Acid during Pregnancy Enhances Neurodevelopment of Fetal Hippocampus

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Huban Thomas Rajarethnem ◽  
Kumar Megur Ramakrishna Bhat ◽  
Malsawmzuali Jc ◽  
Siva Kumar Gopalkrishnan ◽  
Ramesh Babu Mugundhu Gopalram ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Structural Integrity ◽  
Fetal Brain ◽  
Normal Pregnancy ◽  
Saline Control ◽  
Fetal Brain Development ◽  
Essential Nutrient ◽  
Combined Supplementation ◽  
And Function ◽  
The Brain

Choline is an essential nutrient for humans which plays an important role in structural integrity and signaling functions. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, highly enriched in cell membranes of the brain. Dietary intake of choline or DHA alone by pregnant mothers directly affects fetal brain development and function. But no studies show the efficacy of combined supplementation of choline and DHA on fetal neurodevelopment. The aim of the present study was to analyze fetal neurodevelopment on combined supplementation of pregnant dams with choline and DHA. Pregnant dams were divided into five groups: normal control [NC], saline control [SC], choline [C], DHA, and C + DHA. Saline, choline, and DHA were given as supplements to appropriate groups of dams. NC dams were undisturbed during entire gestation. On postnatal day (PND) 40, brains were processed for Cresyl staining. Pups from choline or DHA supplemented group showed significant (p<0.05) increase in number of neurons in hippocampus when compared to the same in NC and SC groups. Moreover, pups from C + DHA supplemented group showed significantly higher number of neurons (p<0.001) in hippocampus when compared to the same in NC and SC groups. Thus combined supplementation of choline and DHA during normal pregnancy enhances fetal hippocampal neurodevelopment better than supplementation of choline or DHA alone.

scholarly journals Bruchpilot, a Protein with Homology to ELKS/CAST, Is Required for Structural Integrity and Function of Synaptic Active Zones in Drosophila

Neuron ◽  
2006 ◽  
Vol 51 (2) ◽  
pp. 275 ◽  
Author(s):  
Dhananjay A. Wagh ◽  
Tobias M. Rasse ◽  
Esther Asan ◽  
Alois Hofbauer ◽  
Isabell Schwenkert ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Active Zones ◽  
And Function

scholarly journals Ecological Effects of Perorally Administered Pivmecillinam on the Normal Vaginal Microflora

2005 ◽  
Vol 49 (1) ◽  
pp. 170-175 ◽  
Author(s):  
Åsa Sullivan ◽  
Aino Fianu-Jonasson ◽  
Britt-Marie Landgren ◽  
Carl Erik Nord
Keyword(s):  
Escherichia Coli ◽  
Candida Albicans ◽  
Antimicrobial Agents ◽  
Ecological Impact ◽  
Menstrual Cycles ◽  
The Third ◽  
Vaginal Microflora ◽  
Normal Microflora ◽  
Facultative Anaerobic ◽  
A Minor

ABSTRACT The knowledge of the effects of antimicrobial agents on the normal vaginal microflora is limited. The objective of the present study was to study the ecological impact of pivmecillinam on the normal vaginal microflora. In 20 healthy women, the estimated day of ovulation was determined during three subsequent menstrual cycles. Microbiological and clinical examinations were performed on the estimated day of ovulation and on day 3 in all cycles and also on day 7 after ovulation in cycles 1 and 2. Anaerobic and facultative anaerobic gram-positive rods, mainly species of lactobacilli and actinomycetes, dominated the microflora. One woman was colonized on the third day of administration with a resistant Escherichia coli strain, and Candida albicans was detected in one woman on days 3 and 7 in cycle 2. No other major changes in the normal microflora occurred during the study. Administration of pivmecillinam had a minor ecological impact on the normal vaginal microflora.

scholarly journals Self-reproducing catalyst drives repeated phospholipid synthesis and membrane growth

2015 ◽  
Vol 112 (27) ◽  
pp. 8187-8192 ◽  
Author(s):  
Michael D. Hardy ◽  
Jun Yang ◽  
Jangir Selimkhanov ◽  
Christian M. Cole ◽  
Lev S. Tsimring ◽  
...  
Keyword(s):  
Lipid Synthesis ◽  
Building Blocks ◽  
Phospholipid Bilayer ◽  
Phospholipid Synthesis ◽  
Synthetic Membranes ◽  
Design And Synthesis ◽  
Membrane Growth ◽  
Membrane Bound ◽  
Living Organisms ◽  
Dynamic Structures

Cell membranes are dynamic structures found in all living organisms. There have been numerous constructs that model phospholipid membranes. However, unlike natural membranes, these biomimetic systems cannot sustain growth owing to an inability to replenish phospholipid-synthesizing catalysts. Here we report on the design and synthesis of artificial membranes embedded with synthetic, self-reproducing catalysts capable of perpetuating phospholipid bilayer formation. Replacing the complex biochemical pathways used in nature with an autocatalyst that also drives lipid synthesis leads to the continual formation of triazole phospholipids and membrane-bound oligotriazole catalysts from simpler starting materials. In addition to continual phospholipid synthesis and vesicle growth, the synthetic membranes are capable of remodeling their physical composition in response to changes in the environment by preferentially incorporating specific precursors. These results demonstrate that complex membranes capable of indefinite self-synthesis can emerge when supplied with simpler chemical building blocks.

Abstract 126: Peroxisomal Proliferator Activated Receptor Alpha Overexpression in Hypertrophied Cardiomyocytes Restores Mitochondrial Integrity and Function

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sagartirtha Sarkar ◽  
Santanu Rana
Keyword(s):  
Energy Demand ◽  
Cardiac Tissue ◽  
Structural Integrity ◽  
Heart Function ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Atp Production ◽  
Receptor Alpha ◽  
And Function

Cardiac tissue engineering is an interdisciplinary field that engineers modulation of viable molecular milieu to restore, maintain or improve heart function. Myocardial workload (energy demand) and energy substrate availability (supply) are in continual flux to maintain specialized cellular processes, yet the heart has a limited capacity for substrate storage and utilization during pathophysiological conditions. Damage to heart muscle, acute or chronic, leads to dysregulation of cardiac metabolic processes associated with gradual but progressive decline in mitochondrial respiratory pathways resulting in diminished ATP production. The Peroxisome Proliferator Activated Receptor Alpha ( PPARα ) is known to regulate fatty acid to glucose metabolic balance as well as mitochondrial structural integrity. In this study, a non-canonical pathway of PPARα was analyzed by cardiomyocyte targeted PPARα overexpression during cardiac hypertrophy that showed significant downregulation in p53 acetylation as well as GSK3β activation levels. Targeted PPARα overexpression during hypertrophy resulted in restoration of mitochondrial structure and function along with significantly improved mitochondrial ROS generation and membrane potential. This is the first report of myocyte targeted PPARα overexpression in hypertrophied myocardium that results in an engineered heart with significantly improved function with increased muscle mitochondrial endurance and reduced mitochondrial apoptotic load, thus conferring a greater resistance to pathological stimuli within cardiac microenvironment.

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