scholarly journals Antifungal Activity of Antimicrobial Peptides and Proteins against Aspergillus fumigatus

2020 ◽  
Vol 6 (2) ◽  
pp. 65
Author(s):  
Eloise Ballard ◽  
Raif Yucel ◽  
Willem J. G. Melchers ◽  
Alistair J. P. Brown ◽  
Paul E. Verweij ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Antimicrobial Peptides ◽  
Aspergillus Fumigatus ◽  
Metabolic Activity ◽  
Hyphal Growth ◽  
Human Fungal Pathogen ◽  
Imaging Flow Cytometry ◽  
Wide Range ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Antimicrobial peptides and proteins (AMPs) provide an important line of defence against invading microorganisms. However, the activity of AMPs against the human fungal pathogen Aspergillus fumigatus remains poorly understood. Therefore, the aim of this study was to characterise the anti-Aspergillus activity of specific human AMPs, and to determine whether A. fumigatus can possess resistance to specific AMPs, as a result of in-host adaptation. AMPs were tested against a wide range of clinical isolates of various origins (including cystic fibrosis patients, as well as patients with chronic and acute aspergillosis). We also tested a series of isogenic A. fumigatus isolates obtained from a single patient over a period of 2 years. A range of environmental isolates, obtained from soil in Scotland, was also included. Firstly, the activity of specific peptides was assessed against hyphae using a measure of fungal metabolic activity. Secondly, the activity of specific peptides was assessed against germinating conidia, using imaging flow cytometry as a measure of hyphal growth. We showed that lysozyme and histones inhibited hyphal metabolic activity in all the A. fumigatus isolates tested in a dose-dependent fashion. In addition, imaging flow cytometry revealed that histones, β-defensin-1 and lactoferrin inhibited the germination of A. fumigatus conidia.

scholarly journals Influence of Human Sera on the In Vitro Activity of the Echinocandin Caspofungin (MK-0991) against Aspergillus fumigatus

2000 ◽  
Vol 44 (12) ◽  
pp. 3302-3305 ◽  
Author(s):  
Tom Chiller ◽  
Kouros Farrokhshad ◽  
Elmer Brummer ◽  
David A. Stevens
Keyword(s):  
Aspergillus Fumigatus ◽  
Human Serum ◽  
Hyphal Growth ◽  
Significant Inhibition ◽  
Dependent Inhibition ◽  
Human Sera ◽  
Dose Dependent Inhibition ◽  
Synthase Inhibitor ◽  
Dose Dependent

ABSTRACT There have been several reports that the activity of echinocandin antifungal agents is not affected or decreased in the presence of human sera. It is known that these drugs are bound >80% in animal and human sera. The activity of the echinocandin caspofungin (MK-0991), a 1,3-β-d-glucan synthase inhibitor, againstAspergillus fumigatus with and without human sera was studied. Conidia of A. fumigatus in microtest plate wells formed germlings after overnight culture in RPMI 1640. Caspofungin was then added with or without serum, and the germlings were incubated at 37°C for 24 h. Human serum (5%) in RPMI 1640 alone did not significantly inhibit the growth of A. fumigatus in vitro. Caspofungin in RPMI 1640 exhibited dose-dependent inhibition, with concentrations of 0.1 and 0.05 μg/ml inhibiting 24.9% +/− 10.4% and 11.7% +/− 3.6%, respectively (n = 10;P < 0.01). The addition of 5% human serum to caspofungin at 0.1 or 0.05 μg/ml increased the inhibition to 78.6% +/− 5.8% or 58.3% +/− 19.2%, respectively (n = 10; P < 0.01 versus controls and versus the drug without serum). Lower concentrations of serum also potentiated drug activity. The effect of human sera was further seen when using caspofungin that had lost activity (e.g., by storage) against A. fumigatus at 0.1 μg/ml. Inactive caspofungin alone demonstrated no significant inhibition of hyphal growth, whereas the addition of 5% human serum to the inactive drug showed 83% +/− 16.5% inhibition (n = 5; P < 0.01). The restoration of activity of caspofungin was seen at concentrations as low as 0.05% human serum. In contrast to prior reports, this study suggests that human serum acts synergistically with caspofungin to enhance its inhibitory activity in vitro against A. fumigatus.

scholarly journals Cathelicidin-inspired antimicrobial peptides as novel antifungal compounds

2020 ◽  
Vol 58 (8) ◽  
pp. 1073-1084
Author(s):  
Martin van Eijk ◽  
Stephanie Boerefijn ◽  
Lida Cen ◽  
Marisela Rosa ◽  
Marnix J H Morren ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Metabolic Activity ◽  
Fungal Infections ◽  
Fungal Species ◽  
Antifungal Compounds ◽  
Candida Auris ◽  
Low Concentrations ◽  
Wide Range ◽  
Eskape Pathogens ◽  
Near Future

Abstract Fungal infections in humans are increasing worldwide and are currently mostly treated with a relative limited set of antifungals. Resistance to antifungals is increasing, for example, in Aspergillus fumigatus and Candida auris, and expected to increase for many medically relevant fungal species in the near future. We have developed and patented a set of cathelicidin-inspired antimicrobial peptides termed ‘PepBiotics’. These peptides were initially selected for their bactericidal activity against clinically relevant Pseudomonas aeruginosa and Staphylococcus aureus isolates derived from patients with cystic fibrosis and are active against a wide range of bacteria (ESKAPE pathogens). We now report results from studies that were designed to investigate the antifungal activity of PepBiotics against a set of medically relevant species encompassing species of Aspergillus, Candida, Cryptococcus, Fusarium, Malassezia, and Talaromyces. We characterized a subset of PepBiotics and show that these peptides strongly affected metabolic activity and/or growth of a set of medically relevant fungal species, including azole-resistant A. fumigatus isolates. PepBiotics showed a strong inhibitory activity against a large variety of filamentous fungi and yeasts species at low concentrations (≤1 μM) and were fungicidal for at least a subset of these fungal species. Interestingly, the concentration of PepBiotics required to interfere with growth or metabolic activity varied between different fungal species or even between isolates of the same fungal species. This study shows that PepBiotics display strong potential for use as novel antifungal compounds to fight a large variety of clinically relevant fungal species.

scholarly journals Aspergillus fumigatus Hyphal Damage Caused by Noninvasive Radiofrequency Field-Induced Hyperthermia

2013 ◽  
Vol 57 (9) ◽  
pp. 4444-4448 ◽  
Author(s):  
Warna D. Kaluarachchi ◽  
Brandon T. Cisneros ◽  
Stuart J. Corr ◽  
Nathaniel D. Albert ◽  
Steven A. Curley ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Treatment Time ◽  
Water Bath ◽  
Severe Damage ◽  
Content Type ◽  
Induced Hyperthermia ◽  
Transmission Electron ◽  
Dose Dependent Fashion ◽  
Dose Dependent

ABSTRACTWe studied the effect of noninvasive radiofrequency-induced hyperthermia on the viability ofAspergillus fumigatushyphaein vitro. Radiofrequency-induced hyperthermia resulted in significant (>70%,P< 0.0001) hyphal damage in a time and thermal dose-dependent fashion as assessed by XTT [(sodium 2,3,-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl] (1)-2H-tetrazolium inner salt)], DiBAC [bis-(1,3-dibutylbarbituric acid) trimethine oxonol] staining, and transmission electron microscopy. For comparison, water bath hyperthermia was used over the range of 45 to 55°C to study hyphal damage. Radiofrequency-induced hyperthermia resulted in severe damage to the outer fibrillar layer of hyphae at a shorter treatment time compared to water bath hyperthermia. Our preliminary data suggest that radiofrequency-induced hyperthermia might be an additional therapeutic approach to use in the management of mold infections.

Plasminogen Interactions with Immobilized Fibrinogen

1989 ◽  
Vol 62 (04) ◽  
pp. 1078-1082 ◽  
Author(s):  
Burt Adelman ◽  
Patricia Ouynn
Keyword(s):  
Immunosorbent Assay ◽  
Aminocaproic Acid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Binding Regions ◽  
Dose Dependent Fashion ◽  
Epsilon Aminocaproic Acid ◽  
Dose Dependent

SummaryThis report describes the binding of plasminogen to fibrinogen adsorbed onto polystyrene wells. Binding was determined by enzyme linked immunosorbent assay. Both glu- and lys-plasminogen bound to immobilized fibrinogen in a dose-dependent fashion. However, more lys- than glu-plasminogen bound when equal concentrations of either were added to immobilized fibrinogen. Plasminogen binding was inhibited by epsilon aminocaproic acid indicating that binding was mediated via lysine-binding regions of plasminogen. Soluble fibrinogen added in excess of immobilized fibrinogen did not compete for plasminogen binding but fibrinogen fragments produced by plasmin digestion of fibrinogen did. Treatment of immobilized fibrinogen with thrombin caused a small but significant (p <0.01) increase in plasminogen binding. These studies demonstrate that immobilized fibrinogen binds both glu- and lys-plasminogen and that binding is mediated via lysine-binding regions. These interactions may facilitate plasminogen binding to fibrinogen adsorbed on to surfaces and to cells such as platelets which bind fibrinogen.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

Antimicrobial Peptides - Small but Mighty Weapons for Plants to Fight Phytopathogens

2019 ◽  
Vol 26 (10) ◽  
pp. 720-742 ◽  
Author(s):  
Kaushik Das ◽  
Karabi Datta ◽  
Subhasis Karmakar ◽  
Swapan K. Datta
Keyword(s):  
Antimicrobial Peptides ◽  
Durable Resistance ◽  
Defense Responses ◽  
Defense System ◽  
Biotechnological Potential ◽  
Functional Aspects ◽  
Low Concentrations ◽  
Wide Range ◽  
Vital Component ◽  
Pathogen Entry

Antimicrobial Peptides (AMPs) have diverse structures, varied modes of actions, and can inhibit the growth of a wide range of pathogens at low concentrations. Plants are constantly under attack by a wide range of phytopathogens causing massive yield losses worldwide. To combat these pathogens, nature has armed plants with a battery of defense responses including Antimicrobial Peptides (AMPs). These peptides form a vital component of the two-tier plant defense system. They are constitutively expressed as part of the pre-existing first line of defense against pathogen entry. When a pathogen overcomes this barrier, it faces the inducible defense system, which responds to specific molecular or effector patterns by launching an arsenal of defense responses including the production of AMPs. This review emphasizes the structural and functional aspects of different plant-derived AMPs, their homology with AMPs from other organisms, and how their biotechnological potential could generate durable resistance in a wide range of crops against different classes of phytopathogens in an environmentally friendly way without phenotypic cost.

scholarly journals In Vitro Cellular Uptake Studies of Self-Assembled Fluorinated Nanoparticles Labelled with Antibodies

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1906
Author(s):  
Mona Atabakhshi-Kashi ◽  
Mónica Carril ◽  
Hossein Mahdavi ◽  
Wolfgang J. Parak ◽  
Carolina Carrillo-Carrion ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cellular Uptake ◽  
Hydrophobic Interactions ◽  
Intrinsic Properties ◽  
Wide Range ◽  
Self Assembled ◽  
Uptake Studies ◽  
Targeting Ability ◽  
Fluorinated Nanoparticles

Nanoparticles (NPs) functionalized with antibodies (Abs) on their surface are used in a wide range of bioapplications. Whereas the attachment of antibodies to single NPs to trigger the internalization in cells via receptor-mediated endocytosis has been widely studied, the conjugation of antibodies to larger NP assemblies has been much less explored. Taking into account that NP assemblies may be advantageous for some specific applications, the possibility of incorporating targeting ligands is quite important. Herein, we performed the effective conjugation of antibodies onto a fluorescent NP assembly, which consisted of fluorinated Quantum Dots (QD) self-assembled through fluorine–fluorine hydrophobic interactions. Cellular uptake studies by confocal microscopy and flow cytometry revealed that the NP assembly underwent the same uptake procedure as individual NPs; that is, the antibodies retained their targeting ability once attached to the nanoassembly, and the NP assembly preserved its intrinsic properties (i.e., fluorescence in the case of QD nanoassembly).

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