scholarly journals Regulation of Antimicrobial Peptide Activity via Tuning Deformation Fields by Membrane-Deforming Inclusions

2021 ◽  
Vol 23 (1) ◽  
pp. 326
Author(s):  
Oleg V. Kondrashov ◽  
Sergey A. Akimov
Keyword(s):  
Antimicrobial Peptides ◽  
Statistical Model ◽  
Antimicrobial Peptide ◽  
Plasma Membranes ◽  
Eukaryotic Cell ◽  
Gramicidin A ◽  
Eukaryotic Cells ◽  
Amphipathic Peptides ◽  
Transmembrane Peptides

Antimicrobial peptides (AMPs) are considered prospective antibiotics. Some AMPs fight bacteria via cooperative formation of pores in their plasma membranes. Most AMPs at their working concentrations can induce lysis of eukaryotic cells as well. Gramicidin A (gA) is a peptide, the transmembrane dimers of which form cation-selective channels in membranes. It is highly toxic for mammalians as being majorly hydrophobic gA incorporates and induces leakage of both bacterial and eukaryotic cell membranes. Both pore-forming AMPs and gA deform the membrane. Here we suggest a possible way to reduce the working concentrations of AMPs at the expense of application of highly-selective amplifiers of AMP activity in target membranes. The amplifiers should alter the deformation fields in the membrane in a way favoring the membrane-permeabilizing states. We developed the statistical model that allows describing the effect of membrane-deforming inclusions on the equilibrium between AMP monomers and cooperative membrane-permeabilizing structures. On the example of gA monomer-dimer equilibrium, the model predicts that amphipathic peptides and short transmembrane peptides playing the role of the membrane-deforming inclusions, even in low concentration can substantially increase the lifetime and average number of gA channels.

NOVEL FAMILY OF PROLINE-RICH ANTIMICROBIAL PEPTIDES INHIBITING BACTERIAL TRANSLATION

2021 ◽  
Vol 1 (19) ◽  
pp. 173-174
Author(s):  
R.N. Kruglikov ◽  
T.V. Ovchinnikova ◽  
P.V. Panteleev
Keyword(s):  
Biological Activity ◽  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Bacterial Cells ◽  
Bacterial Translation

A new proline-rich antimicrobial peptide from alpaca (Vicugnia pacos) was obtained, as well as its modified analogs. The biological activity of the peptides was studied, and also the role of the N- and C-terminal fragments, when acting on bacterial cells, was analyzed.

scholarly journals Induction of the Antimicrobial Peptide CRAMP in the Blood-Brain Barrier and Meninges after Meningococcal Infection

2006 ◽  
Vol 74 (12) ◽  
pp. 6982-6991 ◽  
Author(s):  
Peter Bergman ◽  
Linda Johansson ◽  
Hong Wan ◽  
Allison Jones ◽  
Richard L. Gallo ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Meningococcal Infection ◽  
Blood Brain ◽  
Bactericidal Properties ◽  
Living Species ◽  
The Brain

ABSTRACT Antimicrobial peptides are present in most living species and constitute important effector molecules of innate immunity. Recently, we and others have detected antimicrobial peptides in the brain. This is an organ that is rarely infected, which has mainly been ascribed to the protective functions of the blood-brain barrier (BBB) and meninges. Since the bactericidal properties of the BBB and meninges are not known, we hypothesized that antimicrobial peptides could play a role in these barriers. We addressed this hypothesis by infecting mice with the neuropathogenic bacterium Neisseria meningitidis. Brains were analyzed for expression of the antimicrobial peptide CRAMP by immunohistochemistry in combination with confocal microscopy. After infection, we observed induction of CRAMP in endothelial cells of the BBB and in cells of the meninges. To explore the functional role of CRAMP in meningococcal disease, we infected mice deficient of the CRAMP gene. Even though CRAMP did not appear to protect the brain from invasion of meningococci, CRAMP knockout mice were more susceptible to meningococcal infection than wild-type mice and exhibited increased meningococcal growth in blood, liver, and spleen. Moreover, we could demonstrate that carbonate, a compound that accumulates in the circulation during metabolic acidosis, makes meningococci more susceptible to CRAMP.

scholarly journals Interaction of the Gelsolin-Derived Antibacterial PBP 10 Peptide with Lipid Bilayers and Cell Membranes

2006 ◽  
Vol 50 (9) ◽  
pp. 2932-2940 ◽  
Author(s):  
Robert Bucki ◽  
Paul A. Janmey
Keyword(s):  
Antimicrobial Peptides ◽  
Lipid Bilayers ◽  
Cell Membranes ◽  
Plasma Membranes ◽  
Antimicrobial Activities ◽  
Eukaryotic Cells ◽  
Hypotonic Solution ◽  
Antibacterial Peptides ◽  
Bacterial Killing ◽  
Bacterial Membranes

ABSTRACTPBP 10, an antibacterial, cell membrane-permeant rhodamine B-conjugated peptide derived from the polyphosphoinositide binding site of gelsolin, interacts selectively with both lipopolysaccharides (LPS) and lipoteichoic acid (LTA), the distinct components of gram-negative and gram-positive bacteria, respectively. Isolated LPS and LTA decrease the antimicrobial activities of PBP 10, as well as other antimicrobial peptides, such as cathelicidin-LL37 (LL37) and mellitin. In an effort to elucidate the mechanism of bacterial killing by PBP 10, we compared its effects on artificial lipid bilayers and eukaryotic cell membranes with the actions of the mellitin, magainin II, and LL37 peptides. This study reveals that pore formation is unlikely to be involved in PBP 10-mediated membrane destabilization. We also investigated the effects of these peptides on platelets and red blood cells (RBCs). Comparison of these antimicrobial peptides shows that only mellitin has a toxic effect on platelets and RBCs in a concentration range concomitant with its bactericidal activity. The hemolytic activities of the PBP 10 and LL37 peptides significantly increase when RBCs are osmotically swollen in hypotonic solution, indicating that these antibacterial peptides may take advantage of the more extended form of bacterial membranes in exerting their killing activities. Additionally, we found that LL37 hemolytic activity was much higher when RBCs were induced to expose phosphatidylserine to the external leaflet of their plasma membranes. This finding suggests that asymmetrical distribution of phospholipids in the external membranes of eukaryotic cells may represent an important factor in determining the specificity of antibacterial peptides for targeting bacteria rather than eukaryotic cells.

Mitochondria Are Fundamental for the Emergence of Metazoans: On Metabolism, Genomic Regulation, and the Birth of Complex Organisms

2020 ◽  
Vol 54 (1) ◽  
pp. 151-166 ◽  
Author(s):  
Hadar Medini ◽  
Tal Cohen ◽  
Dan Mishmar
Keyword(s):  
Gene Expression ◽  
Chromatin Remodeling ◽  
Genetic System ◽  
Eukaryotic Cell ◽  
Eukaryotic Cells ◽  
Intracellular Bacteria ◽  
Human Disorders ◽  
Genomic Regulation ◽  
Lines Of Evidence

Out of many intracellular bacteria, only the mitochondria and chloroplasts abandoned their independence billions of years ago and became endosymbionts within the host eukaryotic cell. Consequently, one cannot grow eukaryotic cells without their mitochondria, and the mitochondria cannot divide outside of the cell, thus reflecting interdependence. Here, we argue that such interdependence underlies the fundamental role of mitochondrial activities in the emergence of metazoans. Several lines of evidence support our hypothesis: ( a) Differentiation and embryogenesis rely on mitochondrial function; ( b) mitochondrial metabolites are primary precursors for epigenetic modifications (such as methyl and acetyl), which are critical for chromatin remodeling and gene expression, particularly during differentiation and embryogenesis; and ( c) mitonuclear coregulation adapted to accommodate both housekeeping and tissue-dependent metabolic needs. We discuss the evolution of the unique mitochondrial genetic system, mitochondrial metabolites, mitonuclear coregulation, and their critical roles in the emergence of metazoans and in human disorders.

scholarly journals Resistance of Porphyromonas gingivalis ATCC 33277 to Direct Killing by Antimicrobial Peptides Is Protease Independent

2007 ◽  
Vol 52 (2) ◽  
pp. 638-642 ◽  
Author(s):  
Gilad Bachrach ◽  
Hamutal Altman ◽  
Paul E. Kolenbrander ◽  
Natalia I. Chalmers ◽  
Michal Gabai-Gutner ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Porphyromonas Gingivalis ◽  
Wide Spectrum ◽  
Periodontal Diseases ◽  
Amphipathic Peptides ◽  
Gram Negative ◽  
Protease Deficient ◽  
Direct Killing ◽  
Positively Charged

ABSTRACT Antimicrobial peptides are short, positively charged, amphipathic peptides that possess a wide spectrum of antimicrobial activity and have an important role in the host's innate immunity. Lack of, or dysfunctions in, antimicrobial peptides have been correlated with infectious diseases, including periodontitis. Porphyromonas gingivalis, a gram-negative anaerobe and a major pathogen associated with periodontal diseases, is resistant to antimicrobial peptides of human and nonhuman origin, a feature that likely contributes to its virulence. Expressing a robust proteolytic activity, P. gingivalis hydrolyzes antimicrobial peptides. In this study, P. gingivalis inactivated three antimicrobial peptides, while a d-enantiomer was resistant to degradation. P. gingivalis was resistant to the protease-resistant d-enantiomer peptide, and importantly, a protease-deficient P. gingivalis mutant was also resistant to the antimicrobial peptide. Finally, the binding of a fluorescently labeled antimicrobial peptide to protease-deficient P. gingivalis was much weaker than the binding of susceptible Escherichia coli. Our results suggest that the resistance of P. gingivalis ATCC 33277 to direct killing by antimicrobial peptides is protease independent and results (at least partially) from the low affinity of antimicrobial peptides to P. gingivalis.

scholarly journals Epididymal antimicrobial peptides: the role in sperm function (review)

2021 ◽  
pp. 4-12
Author(s):  
П.А. Шабанов ◽  
О.В. Шамова ◽  
Д.С. Орлов ◽  
А.Ю. Грязнов ◽  
Н.О. Янчук
Keyword(s):  
Antimicrobial Peptides ◽  
Germ Cells ◽  
Plasma Membranes ◽  
Reproductive Tract ◽  
Biological Effects ◽  
Physiological Activity ◽  
Female Reproductive Tract ◽  
Physiological Processes ◽  
Molecular Regulatory Mechanisms

Значительное снижение показателей мужской фертильности, наблюдаемое в последнее время во всем мире, ведёт к необходимости более глубокого изучения механизмов молекулярной регуляции гаметогенеза и посттестикулярной трансформации сперматозоидов. Совершенствование способов влияния на эти процессы, а также поиск веществ, повышающих устойчивость гамет к действию различных повреждающих факторов, открывают перспективы разработки новых подходов в лечении мужского бесплодия. В связи с этим актуальным направлением является исследование роли эндогенных антимикробных пептидов и их физиологической активности при созревании и функционировании мужских половых клеток. Антимикробные пептиды - это уникальные компоненты системы врожденного иммунитета. Они не только обеспечивают противоинфекционную защиту организма от бактерий, вирусов и грибов, но и проявляют достаточно разнообразные биологические эффекты, которые связаны, в том числе и со способностью этих молекул принимать непосредственное участие в физиологических процессах посттестикулярного созревания половых клеток, модификации цитоплазматических мембран сперматозоидов в эпидидимисе, а также капацитации в женском репродуктивном тракте. В настоящем обзоре рассмотрены современные представления о роли антимикробных пептидов придатков яичек с позиций их участия в функционировании сперматозоидов в норме и при патологии. The significant worldwide decline in male fertility requires a comprehensive study of molecular regulatory mechanisms of gametogenesis and post-testicular sperm maturation. Improving ways to influence these processes as well as searching for substances that increase the resistance of gametes to the action of various damaging factors open up prospects for development of new approaches to treat male infertility. In this regard, current emphasis is on the study of a role of endogenous antimicrobial peptides (AMPs) and their physiological activity during the maturation and functioning of male germ cells. AMPs are unique components of the innate immune system. They not only provide protection against bacteria, viruses, and fungi, but also have relatively diverse biological effects. These effects are closely related to the ability of AMPs to be directly involved in the physiological processes of post-testicular maturation of germ cells, in modification of the plasma membranes of sperms in the epididymis, and their capacitation in the female reproductive tract. This review focuses on the current understanding of the role of epididymal AMPs with regard to the functioning of sperm in normal and pathological conditions.

Expression and immunolocalisation of antimicrobial peptides within human palatine tonsils

2007 ◽  
Vol 121 (10) ◽  
pp. 973-978 ◽  
Author(s):  
S L Ball ◽  
G P Siou ◽  
J A Wilson ◽  
A Howard ◽  
B H Hirst ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Surface Epithelium ◽  
Cationic Peptides ◽  
Cationic Peptide ◽  
Acute Tonsillitis ◽  
Palatine Tonsils ◽  
Control Subjects ◽  
Peptide Expression

Background: Recurrent acute tonsillitis is one of the most frequent ENT referrals, yet its pathogenesis remains poorly understood, and tonsillectomy still costs the National Health Service more than £60 000 000 annually. Antimicrobial cationic peptides are components of the innate immune system. They are generally small, highly positively charged peptides with broad spectrum antimicrobial activity which function as the body's ‘natural antibiotics'. The role of antimicrobial cationic peptides in the susceptibility of patients to recurrent acute tonsillitis is unknown.Aims: To characterise and compare antimicrobial cationic peptide expression and localisation in human palatine tonsils from control subjects and recurrent acute tonsillitis patients, and to assess the potential role of these peptides in the pathogenesis of tonsillitis.Methods: Palatine tonsils were harvested with informed consent from 19 recurrent acute tonsillitis patients and from five control subjects undergoing tonsillectomy for sleep disorders. Total ribonucleic acid was isolated and antimicrobial cationic peptide expression was characterised using reverse transcription polymerase chain reaction. Fluorescent immunohistochemical techniques were used to localise antimicrobial cationic peptides within fresh frozen tonsil sections.Results: Using molecular analyses, the palatine tonsils from control and recurrent acute tonsillitis subjects were confirmed as a site of expression of the antimicrobial cationic peptides human β-defensin 1–3, LL-37 (cathelicidin) and Liver expressed antimicrobial peptide-1 (LEAP-1). We also demonstrated for the first time the expression of Liver expressed antimicrobial peptide-2 (LEAP-2). Our analyses indicated that all six antimicrobial cationic peptides were expressed in all 26 tonsil samples. Immunohistochemical staining indicated that the antimicrobial cationic peptides were localised to the tonsil surface and crypt epithelium. However, the surface epithelium of tonsils from recurrent acute tonsillitis patients showed reduced amounts of antimicrobial peptides human β-defensins 1 and 3, and LL-37, compared with healthy controls.Conclusion: The tonsil epithelium synthesises an array of antimicrobial cationic peptides which function as host defence. Preliminary immunohistochemical data suggest that the surface epithelium of tonsils from recurrent acute tonsillitis patients contains reduced amounts of such peptides, which may increase these patients' susceptibility to infection.

Antimicrobial Peptides: A Promising Avenue for Human Healthcare

2020 ◽  
Vol 21 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Girish M. Bhopale
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Antimicrobial Agents ◽  
Current Status ◽  
Antimicrobial Drugs ◽  
Spectrum Activity ◽  
Low Levels ◽  
Human Healthcare ◽  
Broad Spectrum Activity ◽  
Promising Avenue

Antimicrobial drugs resistant microbes have been observed worldwide and therefore alternative development of antimicrobial peptides has gained interest in human healthcare. Enormous progress has been made in the development of antimicrobial peptide during the last decade due to major advantages of AMPs such as broad-spectrum activity and low levels of induced resistance over the current antimicrobial agents. This review briefly provides various categories of AMP, their physicochemical properties and mechanism of action which governs their penetration into microbial cell. Further, the recent information on current status of antimicrobial peptide development, their applications and perspective in human healthcare are also described.

High Mobility Group Box-1 (HMGB1): A Potential Target in Therapeutics

2019 ◽  
Vol 20 (14) ◽  
pp. 1474-1485 ◽  
Author(s):  
Eyaldeva C. Vijayakumar ◽  
Lokesh Kumar Bhatt ◽  
Kedar S. Prabhavalkar
Keyword(s):  
Myocardial Infarction ◽  
Vagus Nerve Stimulation ◽  
Nuclear Protein ◽  
Therapeutic Potential ◽  
High Mobility ◽  
Dna Binding Protein ◽  
High Mobility Group ◽  
Eukaryotic Cells ◽  
Hmgb1 Protein

High mobility group box-1 (HMGB1) mainly belongs to the non-histone DNA-binding protein. It has been studied as a nuclear protein that is present in eukaryotic cells. From the HMG family, HMGB1 protein has been focused particularly for its pivotal role in several pathologies. HMGB-1 is considered as an essential facilitator in diseases such as sepsis, collagen disease, atherosclerosis, cancers, arthritis, acute lung injury, epilepsy, myocardial infarction, and local and systemic inflammation. Modulation of HMGB1 levels in the human body provides a way in the management of these diseases. Various strategies, such as HMGB1-receptor antagonists, inhibitors of its signalling pathway, antibodies, RNA inhibitors, vagus nerve stimulation etc. have been used to inhibit expression, release or activity of HMGB1. This review encompasses the role of HMGB1 in various pathologies and discusses its therapeutic potential in these pathologies.

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