scholarly journals The Double-Edged Sword of Beta2-Microglobulin in Antibacterial Properties and Amyloid Fibril-Mediated Cytotoxicity

2021 ◽  
Vol 22 (12) ◽  
pp. 6330
Author(s):  
Shean-Jaw Chiou ◽  
Huey-Jiun Ko ◽  
Chi-Ching Hwang ◽  
Yi-Ren Hong
Keyword(s):  
Antimicrobial Activity ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Cytotoxic T Lymphocyte ◽  
Antibacterial Properties ◽  
Physiological Role ◽  
Surface Protein ◽  
Innate Defense ◽  
Wide Range

Beta2-microglobulin (B2M) a key component of major histocompatibility complex class I molecules, which aid cytotoxic T-lymphocyte (CTL) immune response. However, the majority of studies of B2M have focused only on amyloid fibrils in pathogenesis to the neglect of its role of antimicrobial activity. Indeed, B2M also plays an important role in innate defense and does not only function as an adjuvant for CTL response. A previous study discovered that human aggregated B2M binds the surface protein structure in Streptococci, and a similar study revealed that sB2M-9, derived from native B2M, functions as an antibacterial chemokine that binds Staphylococcus aureus. An investigation of sB2M-9 exhibiting an early lymphocyte recruitment in the human respiratory epithelium with bacterial challenge may uncover previously unrecognized aspects of B2M in the body’s innate defense against Mycobactrium tuberculosis. B2M possesses antimicrobial activity that operates primarily under pH-dependent acidic conditions at which B2M and fragmented B2M may become a nucleus seed that triggers self-aggregation into distinct states, such as oligomers and amyloid fibrils. Modified B2M can act as an antimicrobial peptide (AMP) against a wide range of microbes. Specifically, these AMPs disrupt microbe membranes, a feature similar to that of amyloid fibril mediated cytotoxicity toward eukaryotes. This study investigated two similar but nonidentical effects of B2M: the physiological role of B2M, in which it potentially acts against microbes in innate defense and the role of B2M in amyloid fibrils, in which it disrupts the membrane of pathological cells. Moreover, we explored the pH-governing antibacterial activity of B2M and acidic pH mediated B2M amyloid fibrils underlying such cytotoxicity.

scholarly journals Subinhibitory Antimicrobial Concentrations: A Review of In Vitro and In Vivo Data

1992 ◽  
Vol 3 (4) ◽  
pp. 193-201 ◽  
Author(s):  
George G Zhanel ◽  
Daryl J Hoban ◽  
Godfrey KM Harding
Keyword(s):  
Antimicrobial Activity ◽  
Animal Studies ◽  
Molecular Level ◽  
Bacterial Virulence ◽  
Antibacterial Effects ◽  
Wide Range ◽  
Immune Defences

Antimicrobial activity is not an ‘all or none’ effect. An increase in the rate and extent of antimicrobial action is usually observed over a wide range of antimicrobial concentrations. Subinhibitory antimicrobial concentrations are well known to produce significant antibacterial effects, and various antimicrobials at subinhibitory concentrations have been reported to inhibit the rate of bacterial growth. Bacterial virulence may be increased or decreased by subinhibitory antimicrobial concentrations by changes in the ability of bacteria to adhere to epithelial cells or by alterations in bacterial susceptibility to host immune defences. Animal studies performed in rats, hamsters and rabbits demonstrate decreased bacterial adherence, reduced infectivity and increased survival of animals treated with subinhibitory antimicrobial concentrations compared to untreated controls. The major future role of investigation of subinhibitory antimicrobial concentrations will be to define more fully, at a molecular level, how antimicrobials exert their antibacterial effects.

Antioxidant and Antimicrobial Activities of the Fresh aerial parts of Ammi visnaga L. from Algeria

2016 ◽  
Vol 6 (2) ◽  
pp. 70-76
Author(s):  
Soumia Keddari ◽  
Narimen Benaoum ◽  
Yasmina Mokhtaria Boufadi ◽  
Mansouria Belhocine ◽  
Ali Riazi
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Phenolic Compounds ◽  
Biological Activities ◽  
Antibacterial Properties ◽  
Ethanolic Extract ◽  
Diffusion Method ◽  
E Coli ◽  
Ammi Visnaga ◽  
Wide Range

Medicinal plants have been used for countries as cures for human diseases because they contain components of therapeutic value. Among these medi-cinal plants, Ammi visnage which have an immense reservoir of potential compounds attributed to the secondary metabolites which have the advan-tage of being of great diversity of chemical structure and have a very wide range of biological activities. The objectives of the present work were to stu-dy the antioxidant and antimicrobial activity of phenolic compounds ex-tracted from A. visnaga L. Its extraction is performed by two methods, etha-nol extraction and water extraction. The results showed that A. visnaga L.. ethanolic extract contains a mixture of phytochemical classes as polyphenol, flavonoids and revealed that this plant has high antioxidant activity (IC50 0.069 mg/ml). Regarding the antimicrobial activity results expressed by the diameter of the inhibition zones by diffusion method AWDT, the most signifi-cant inhibition was observed against to Staphylococcus aureus (12 mm) to the ethanol extract at concentration of 100mg / ml. Thus the aqueous ex-tract had a significant inhibitory activity against on the strains Staphylococ-cus aureus (8 mm), E. coli ATCC 10536 (8 mm) to a concentration of 100 mg / ml. The results for the antibacterial properties have shown that Gram-positive bacteria (Staphylococcus aureus, Listeria monocytogenes and M. luteus.) were more sensitive than gram-negative (Pseudomonas aeruginosa, E. coli ATCC 10536) against from the action of phenolic compounds of the Ammi visnaga ethanolic extract.

Protein Fibrillar Nanopolymers: Molecular-Level Insights into Their Structural, Physical and Mechanical Properties

2015 ◽  
Vol 10 (03) ◽  
pp. 135-156 ◽  
Author(s):  
Valeriya M. Trusova
Keyword(s):  
Protein Misfolding ◽  
Amyloid Fibrils ◽  
Molecular Level ◽  
Physical And Mechanical Properties ◽  
Present Contribution ◽  
Wide Range ◽  
Generic Class ◽  
Protein Fibril

Amyloid fibrils represent a generic class of mechanically strong and stable biomaterials with extremely advantageous properties. Although amyloids were initially associated only with severe neurological disorders, the role of these structures nowadays is shifting from health debilitating to highly beneficial both in biomedical and technological aspects. Intensive involvement of fibrillar assemblies into the wide range of pathogenic and functional processes strongly necessitate the molecular level characterization of the structural, physical and elastic features of protein nanofibrils. In the present contribution, we made an attempt to highlight the up-to-date progress in the understanding of amyloid properties from the polymer physics standpoint. The fundamental insights into protein fibril behavior are essential not only for development of therapeutic strategies to combat the protein misfolding disorders but also for rational and precise design of novel biodegradable protein-based nanopolymers.

scholarly journals What Can the Kinetics of Amyloid Fibril Formation Tell about Off-pathway Aggregation?

2015 ◽  
Vol 291 (4) ◽  
pp. 2018-2032 ◽  
Author(s):  
Rosa Crespo ◽  
Eva Villar-Alvarez ◽  
Pablo Taboada ◽  
Fernando A. Rocha ◽  
Ana M. Damas ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Pathogenic Role ◽  
Amyloid Deposits ◽  
Amyloid Fibril Formation ◽  
Microscopy Techniques ◽  
Analytical Tools ◽  
Kinetics Of ◽  
Quantitative Importance

Some of the most prevalent neurodegenerative diseases are characterized by the accumulation of amyloid fibrils in organs and tissues. Although the pathogenic role of these fibrils has not been completely established, increasing evidence suggests off-pathway aggregation as a source of toxic/detoxicating deposits that still remains to be targeted. The present work is a step toward the development of off-pathway modulators using the same amyloid-specific dyes as those conventionally employed to screen amyloid inhibitors. We identified a series of kinetic signatures revealing the quantitative importance of off-pathway aggregation relative to amyloid fibrillization; these include non-linear semilog plots of amyloid progress curves, highly variable end point signals, and half-life coordinates weakly influenced by concentration. Molecules that attenuate/intensify the magnitude of these signals are considered promising off-pathway inhibitors/promoters. An illustrative example shows that amyloid deposits of lysozyme are only the tip of an iceberg hiding a crowd of insoluble aggregates. Thoroughly validated using advanced microscopy techniques and complementary measurements of dynamic light scattering, CD, and soluble protein depletion, the new analytical tools are compatible with the high-throughput methods currently employed in drug discovery.

scholarly journals Antimicrobial Activity of Se-Nanoparticles from Bacterial Biotransformation

Fermentation ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. 130
Author(s):  
Meyli Claudia Escobar-Ramírez ◽  
Araceli Castañeda-Ovando ◽  
Emmanuel Pérez-Escalante ◽  
Gabriela Mariana Rodríguez-Serrano ◽  
Esther Ramírez-Moreno ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Pathogenic Bacteria ◽  
Negative Charge ◽  
Antibacterial Properties ◽  
Growth Conditions ◽  
Bacteria Growth ◽  
Microbial Inhibition ◽  
Wide Range ◽  
Main Factors ◽  
Biological Methods

Selenium nanoparticles (SeNPs) are gaining importance in the food and medical fields due to their antibacterial properties. The microbial inhibition of these kinds of particles has been tested in a wide range of Gram (+) and Gram (−) pathogenic bacteria. When SeNPs are synthesized by biological methods, they are called biogenic SeNPs, which have a negative charge caused by their interaction between surface and capping layer (bioorganic material), producing their high stability. This review is focused on SeNPs synthesis by bacteria and summarizes the main factors that influence their main characteristics: shape, size and surface charge, considering the bacteria growth conditions for their synthesis. The different mechanisms of antimicrobial activity are revised, and this review describes several biosynthesis hypotheses that have been proposed due to the fact that the biological mechanism of SeNP synthesis is not fully known.

scholarly journals A Systematic Review of Serum γ-Glutamyltransferase as a Prognostic Biomarker in Patients with Genitourinary Cancer

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 549
Author(s):  
Kosuke Takemura ◽  
Philip G. Board ◽  
Fumitaka Koga
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Cancer Cells ◽  
Elevated Serum ◽  
Physiological Role ◽  
Epidemiological Studies ◽  
Genitourinary Cancer ◽  
Increased Risk ◽  
Wide Range

γ-Glutamyltransferase (GGT), a membrane-bound enzyme, contributes to the metabolism of glutathione (GSH), which plays a critical physiological role in protecting cells against oxidative stress. GGT has been proposed as a biomarker of carcinogenesis and tumor progression given that GGT activity is important during both the promotion and invasion phases in cancer cells. Moreover, GGT expression is reportedly related to drug-resistance possibly because a wide range of drugs are conjugated with GSH, the availability of which is influenced by GGT activity. While serum GGT activity is commonly used as a quick, inexpensive, yet reliable means of assessing liver function, recent epidemiological studies have shown that it may also be an indicator of an increased risk of prostate cancer development. Moreover, elevated serum GGT is reportedly an adverse prognostic predictor in patients with urologic neoplasms, including renal cell carcinoma, prostate cancer, and urothelial carcinoma, although the background mechanisms have still not been well-characterized. The present review article summarizes the possible role of GGT in cancer cells and focuses on evidence evaluation through a systematic review of the latest literature on the prognostic role of serum GGT in patients with genitourinary cancer.

scholarly journals Role of Pre-molten Globule Structure in Protein Amyloid Fibril Formation

2019 ◽  
Vol 7 (1) ◽  
pp. 35-42
Author(s):  
Ali Es-haghi ◽  
Mahsa Jahedi Moghaddam ◽  
Koorosh Shahpasand
Keyword(s):  
Protein Aggregation ◽  
Protein Unfolding ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Molten Globule ◽  
Critical Event ◽  
Diabetic Mellitus ◽  
Native Conformation ◽  
Amyloid Fibril Formation

The conversion of a protein from its native conformation to the pathogenic form is a critical event in the pathogenesis of several neurodegenerative disorders such as Alzheimer’s (AD), Parkinson’s, and Huntington’s diseases, along with type II diabetic mellitus. Although there are several reports on the mechanism of protein aggregation, the actual conformation playing a part in the pathogenicity is yet unclear. Accordingly, the present study summarizes the early pathogenic conformation resulting in several protein aggregations. It is well-documented that a pre-molten globule (MG) structure appears at the early stages of some proteins. Pre-MG is one of the intermediate structures, which is formed during some protein unfolding processes. In addition, it is shown that the pre-molten structure is more flexible than the mature MG one and thus, protein easily rearranges to form amyloid fibrils in this conformation. Therefore, protein aggregation is halted by preventing the pre-MG structure. The strategy of protein aggregation prevention has profound implications in fighting the devastating disorder.

scholarly journals Liquid condensates increase potency of amyloid fibril inhibitors

2020 ◽  
Author(s):  
Thomas C. T. Michaels ◽  
L. Mahadevan ◽  
Christoph A. Weber
Keyword(s):  
Phase Separation ◽  
Protein Aggregation ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Amyloid Formation ◽  
Physiological Processes ◽  
Parkinson’S Diseases ◽  
Spatio Temporal ◽  
Liquid Condensate

In living cells, liquid condensates form in the cytoplasm and nucleoplasm via phase separation and regulate physiological processes. They also regulate aberrant aggregation of amyloid fibrils, a process linked to Alzheimer’s and Parkinson’s diseases. In the absence of condensates it has been shown that amyloid aggregation can be inhibited by molecular chaperones and rationally designed drugs. However it remains unknown how this drug- or chaperone-mediated inhibition of amyloid fibril aggregation is affected by phase-separated condensates. Here we study the interplay between protein aggregation, its inhibition and liquid-liquid phase separation. Our key finding is that the potency of inhibitors of amyloid formation can be strongly enhanced. We show that the corresponding mechanism relies on the colocalization of inhibitors and aggregates inside the liquid condensate. We provide experimentally testable physicochemical conditions under which the increase of inhibitor potency is most pronounced. Our work highlights the role of spatio-temporal heterogeneity in curtailing aberrant protein aggregation and suggests design principles for amyloid inhibitors accounting for partitioning of drugs into liquid condensates.

scholarly journals Structural states of a RNA aptamer, molecular dynamics simulation study

2016 ◽  
Author(s):  
Ida Autiero ◽  
Luigi Vitagliano ◽  
Roberto Improta ◽  
Menotti - Ruvo
Keyword(s):  
Rna Folding ◽  
Physiological Role ◽  
Bound State ◽  
Dynamics Simulation ◽  
Free State ◽  
Rna Aptamer ◽  
Dynamic Features ◽  
Structural Arrangement ◽  
Wide Range

Motivation RNA, which adopts a wide range of secondary structures is involved in several kind of chemical interactions and shows a notable structural plasticity. Due to remarkable chemical properties and an important physiological role of RNAs, there is a growing interest in development of RNA-based drugs and ligands of clinical relevance. However, RNAs structural and dynamic features as well as the main RNA-protein recognition effects remain largely unaddressed. We have studied the conformational behaviour and the dynamic of two different structural arrangements of an aptamer binding the bacillus anthracis ribosomal protein S8. This RNA aptamer has experimentally shown two different topologies in free state and in protein-bound state, although sequences differ for just few residues beyond the common internal loop. The role of the interacting protein on the RNA folding, stabilizing or inducing a particular conformation will be discussed. Methods Three molecular dynamic simulations of 300 ns each have been performed starting from three distinct aptamer structures: i) the aptamer free-state, using a representative model of a NMR ensemble of structures (pdb 2lun); ii) a similar aptamer bound to its target protein (4pdb) iii); an aptamer model built using the sequence of the RNA in the free state but with the structural arrangement of the bound-state to investigate a possible influence of the sequence on the RNA folding. All the systems under investigations were solvated in a truncated octahedral water box using explicit water models, with a least a 1.1 Å distance to the border, using Na+ counter-ions to neutralize. 6 steps of heating simulation from 50 K to 300K were carried out before to perform the final MD run of 300 ns in NPT conditions without restrains. The trajectories were analysed using the GROMACS utilities and X3DNA program. Results Our data show that both bound-state RNA arrangements are structurally stable, holding all the main interactions since the beginning of the simulations. The free-state RNA is the system with the largest flexibility, reaching an equilibrium after 40 ns of simulation. Although the NMR structure appears less rigid, during the total run it never matches the arrangement of the bound state. Definitely, within our time scale, a convergence of the free state with the bound-state trajectories has never been observed and the two different arrangements show differences in flexibility. Preliminary data suggest a significantly different behaviour of the free- and bound-state structures supporting a preminent role of the interacting partner protein on the RNA overall folding to induce a particular stable structural arrangement.

scholarly journals Structural states of a RNA aptamer, molecular dynamics simulation study

2016 ◽  
Author(s):  
Ida Autiero ◽  
Luigi Vitagliano ◽  
Roberto Improta ◽  
Menotti - Ruvo
Keyword(s):  
Rna Folding ◽  
Physiological Role ◽  
Bound State ◽  
Dynamics Simulation ◽  
Free State ◽  
Rna Aptamer ◽  
Dynamic Features ◽  
Structural Arrangement ◽  
Wide Range

Motivation RNA, which adopts a wide range of secondary structures is involved in several kind of chemical interactions and shows a notable structural plasticity. Due to remarkable chemical properties and an important physiological role of RNAs, there is a growing interest in development of RNA-based drugs and ligands of clinical relevance. However, RNAs structural and dynamic features as well as the main RNA-protein recognition effects remain largely unaddressed. We have studied the conformational behaviour and the dynamic of two different structural arrangements of an aptamer binding the bacillus anthracis ribosomal protein S8. This RNA aptamer has experimentally shown two different topologies in free state and in protein-bound state, although sequences differ for just few residues beyond the common internal loop. The role of the interacting protein on the RNA folding, stabilizing or inducing a particular conformation will be discussed. Methods Three molecular dynamic simulations of 300 ns each have been performed starting from three distinct aptamer structures: i) the aptamer free-state, using a representative model of a NMR ensemble of structures (pdb 2lun); ii) a similar aptamer bound to its target protein (4pdb) iii); an aptamer model built using the sequence of the RNA in the free state but with the structural arrangement of the bound-state to investigate a possible influence of the sequence on the RNA folding. All the systems under investigations were solvated in a truncated octahedral water box using explicit water models, with a least a 1.1 Å distance to the border, using Na+ counter-ions to neutralize. 6 steps of heating simulation from 50 K to 300K were carried out before to perform the final MD run of 300 ns in NPT conditions without restrains. The trajectories were analysed using the GROMACS utilities and X3DNA program. Results Our data show that both bound-state RNA arrangements are structurally stable, holding all the main interactions since the beginning of the simulations. The free-state RNA is the system with the largest flexibility, reaching an equilibrium after 40 ns of simulation. Although the NMR structure appears less rigid, during the total run it never matches the arrangement of the bound state. Definitely, within our time scale, a convergence of the free state with the bound-state trajectories has never been observed and the two different arrangements show differences in flexibility. Preliminary data suggest a significantly different behaviour of the free- and bound-state structures supporting a preminent role of the interacting partner protein on the RNA overall folding to induce a particular stable structural arrangement.

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