scholarly journals Adhesins in Human Fungal Pathogens: Glue with Plenty of Stick

2013 ◽  
Vol 12 (4) ◽  
pp. 470-481 ◽  
Author(s):  
Piet W. J. de Groot ◽  
Oliver Bader ◽  
Albert D. de Boer ◽  
Michael Weig ◽  
Neeraj Chauhan

ABSTRACTUnderstanding the pathogenesis of an infectious disease is critical for developing new methods to prevent infection and diagnose or cure disease. Adherence of microorganisms to host tissue is a prerequisite for tissue invasion and infection. Fungal cell wall adhesins involved in adherence to host tissue or abiotic medical devices are critical for colonization leading to invasion and damage of host tissue. Here, with a main focus on pathogenicCandidaspecies, we summarize recent progress made in the field of adhesins in human fungal pathogens and underscore the importance of these proteins in establishment of fungal diseases.

2013 ◽  
Vol 66 ◽  
pp. 170-177 ◽  
Author(s):  
J.L. Vanneste

In the last few years the causal agent of bacterial canker of kiwifruit Pseudomonas syringae pv actinidiae (Psa) has become a global pathogen of economic importance Since the beginning of this global outbreak many laboratories in the world have been working on Psa Today it is known that Psa is not a homogeneous pathovar and tools that allow the distinction between biovars (subpathovar classification) have been developed The whole genome sequence of several strains of Psa has now been published Some of the assumptions on the life cycle (ports of entry epiphytic survival etc) made in the early days of the outbreak have now been confirmed Although few new methods have been found to control Psa there is now a better understanding of how to reduce the incidence of this disease This paper reviews the progress made in understanding the pathogen the disease and how to control it


Author(s):  
Chiara Burlina ◽  
Eleonora Di Maria

Purpose This paper aims to provide a snapshot of various countries’ contributions to value produced along global value chains (GVCs). It focusses on manufacturing activities and their evolution over time, in the context of GVC regionalisation. Design/methodology/approach The Trade in Value Added (TiVA) and World Integrated Trade Solution databases for the period of 2005-2015 were used to explore the case of Italy and its industries’ specialisations (Made in Italy): fashion, furniture, automotive and machinery traditionally organised into clusters. Various analyses were used to show the dynamics of gross import–export and imported–exported value-added. Moreover, the revealed comparative advantage index was computed to test whether the Made in Italy sector remains a source of competitive advantage for Italy within GVCs. Findings The results highlight how the geography of value-added is changing over time, with growing importance placed on the countries close to Italy and with a different pace according to each considered GVC. Originality/value The paper applied new methods to compare trade and analyse value-added dynamics through a recent database released by the Organization for Economic Co-operation and Development within the TiVA initiative that is useful for scholars and policymakers.


2018 ◽  
Vol 86 (10) ◽  
Author(s):  
Brittany G. Seman ◽  
Jessica L. Moore ◽  
Allison K. Scherer ◽  
Bailey A. Blair ◽  
Sony Manandhar ◽  
...  

ABSTRACTCandida albicansdimorphism is a crucial virulence factor during invasive candidiasis infections, which claim the lives of nearly one-half of those afflicted. It has long been believed that filaments drive tissue invasion and yeast mediates bloodstream dissemination, but observation of these activities during infection has been prevented by technical limitations. We used a transparent zebrafish infection model to analyze more comprehensively howC. albicansutilizes shape to disseminate and invade. This model facilitated the use of diverse, complementary strategies to manipulate shape, allowing us to monitor dissemination, invasion, and pathogenesis via intravital imaging of individual fungal cells throughout the host. To control fungal cell shape, we employed three different strategies: gene deletion (efg1Δ/Δcph1Δ/Δ,eed1Δ/Δ), overexpression of master regulators (NRG1orUME6), and modulation of the infection temperature (21°C, 28°C, or 33°C). The effects of these orthogonal manipulations were consistent, support the proposed specialized roles of yeast in dissemination and filaments in tissue invasion and pathogenesis, and indicate conserved mechanisms in zebrafish. To test if either morphotype changes the effectiveness of the other, we infected fish with a known mixture of shape-locked strains. Surprisingly, mixed-strain infections were associated with additive, but not synergistic, filament invasion and yeast dissemination. These findings provide the most complete view of morphotype-function relationships forC. albicansto date, revealing independent roles of yeast and filaments during disseminated candidiasis.


mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Suresh Ambati ◽  
Aileen R. Ferarro ◽  
S. Earl Kang ◽  
Jianfeng Lin ◽  
Xiaorong Lin ◽  
...  

The fungus Aspergillus fumigatus causes pulmonary invasive aspergillosis resulting in nearly 100,000 deaths each year. Patients are often treated with antifungal drugs such as amphotericin B (AmB) loaded into liposomes (AmB-LLs), but all antifungal drugs, including AmB-LLs, have serious limitations due to human toxicity and insufficient fungal cell killing. Even with the best current therapies, 1-year survival among patients with invasive aspergillosis is only 25 to 60%. Hence, there is a critical need for improved antifungal therapeutics. Dectin-1 is a mammalian protein that binds to beta-glucan polysaccharides found in nearly all fungal cell walls. We coated AmB-LLs with Dectin-1 to make DEC-AmB-LLs. DEC-AmB-LLs bound strongly to fungal cells, while AmB-LLs had little affinity. DEC-AmB-LLs killed or inhibited A. fumigatus 10 times more efficiently than untargeted liposomes, decreasing the effective dose of AmB. Dectin-1-coated drug-loaded liposomes targeting fungal pathogens have the potential to greatly enhance antifungal therapeutics.


mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Nicole M. Revie ◽  
Nicole Robbins ◽  
Luke Whitesell ◽  
John R. Frost ◽  
Solomon D. Appavoo ◽  
...  

ABSTRACT Opportunistic pathogens of the genus Candida reign as the leading cause of mycotic disease and are associated with mortality rates greater than 40%, even with antifungal intervention. This is in part due to the limited arsenal of antifungals available to treat systemic fungal infections. Azoles have been the most widely deployed class of antifungal drug for decades and function by targeting the biosynthesis of ergosterol, a key component of the fungal cell membrane. However, their utility is compromised by their fungistatic nature, which favors the development of resistance. Combination therapy has the potential to confer enhanced efficacy as well as mitigate the evolution of resistance. Previously, we described the generation of structurally diverse macrocyclic peptides with a 1,3,4-oxadiazole and an endocyclic amine grafted within the peptide backbone. Importantly, this noncanonical backbone displayed high membrane permeability, an important attribute for compounds that need to permeate across the fungal cell wall and membrane in order to reach their intracellular target. Here, we explored the bioactivity of this novel chemical scaffold on its own and in combination with the azole fluconazole. Although few of the oxadiazole-containing macrocyclic peptides displayed activity against Candida albicans on their own, many increased the efficacy of fluconazole, resulting in a synergistic combination that was independent of efflux inhibition. Interestingly, these molecules also enhanced azole activity against several non-albicans Candida species, including the azole-resistant pathogens Candida glabrata and Candida auris. This work characterizes a novel chemical scaffold that possesses azole-potentiating activity against clinically important Candida species. IMPORTANCE Fungal infections, such as those caused by pathogenic Candida species, pose a serious threat to human health. Treating these infections relies heavily on the use of azole antifungals; however, resistance to these drugs develops readily, demanding novel therapeutic strategies. This study characterized the antifungal activity of a series of molecules that possess unique chemical attributes and the ability to traverse cellular membranes. We observed that many of the compounds increased the activity of the azole fluconazole against Candida albicans, without blocking the action of drug efflux pumps. These molecules also increased the efficacy of azoles against other Candida species, including the emerging azole-resistant pathogen Candida auris. Thus, we describe a novel chemical scaffold with broad-spectrum bioactivity against clinically important fungal pathogens.


2014 ◽  
Vol 58 (4) ◽  
pp. 2240-2248 ◽  
Author(s):  
Soledad R. Ordonez ◽  
Ilham H. Amarullah ◽  
Richard W. Wubbolts ◽  
Edwin J. A. Veldhuizen ◽  
Henk P. Haagsman

ABSTRACTAntifungal mechanisms of action of two cathelicidins, chicken CATH-2 and human LL-37, were studied and compared with the mode of action of the salivary peptide histatin 5 (Hst5).Candida albicanswas used as a model organism for fungal pathogens. Analysis by live-cell imaging showed that the peptides killC. albicansrapidly. CATH-2 is the most active peptide and killsC. albicanswithin 5 min. Both cathelicidins induce cell membrane permeabilization and simultaneous vacuolar expansion. Minimal fungicidal concentrations (MFC) are in the same order of magnitude for all three peptides, but the mechanisms of antifungal activity are very different. The activity of cathelicidins is independent of the energy status of the fungal cell, unlike Hst5 activity. Live-cell imaging using fluorescently labeled peptides showed that both CATH-2 and LL-37 quickly localize to theC. albicanscell membrane, while Hst5 was mainly directed to the fungal vacuole. Small amounts of cathelicidins internalize at sub-MFCs, suggesting that intracellular activities of the peptide could contribute to the antifungal activity. Analysis by flow cytometry indicated that CATH-2 significantly decreasesC. albicanscell size. Finally, electron microscopy showed that CATH-2 affects the integrity of the cell membrane and nuclear envelope. It is concluded that the general mechanisms of action of both cathelicidins are partially similar (but very different from that of Hst5). CATH-2 has unique features and possesses antifungal potential superior to that of LL-37.


2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.


2021 ◽  
Vol 11 (7) ◽  
pp. 2971
Author(s):  
Siwei Tao ◽  
Congxiao He ◽  
Xiang Hao ◽  
Cuifang Kuang ◽  
Xu Liu

Numerous advances have been made in X-ray technology in recent years. X-ray imaging plays an important role in the nondestructive exploration of the internal structures of objects. However, the contrast of X-ray absorption images remains low, especially for materials with low atomic numbers, such as biological samples. X-ray phase-contrast images have an intrinsically higher contrast than absorption images. In this review, the principles, milestones, and recent progress of X-ray phase-contrast imaging methods are demonstrated. In addition, prospective applications are presented.


Nanomaterials ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 28
Author(s):  
Anastasios I. Tsiotsias ◽  
Nikolaos D. Charisiou ◽  
Ioannis V. Yentekakis ◽  
Maria A. Goula

CO2 methanation has recently emerged as a process that targets the reduction in anthropogenic CO2 emissions, via the conversion of CO2 captured from point and mobile sources, as well as H2 produced from renewables into CH4. Ni, among the early transition metals, as well as Ru and Rh, among the noble metals, have been known to be among the most active methanation catalysts, with Ni being favoured due to its low cost and high natural abundance. However, insufficient low-temperature activity, low dispersion and reducibility, as well as nanoparticle sintering are some of the main drawbacks when using Ni-based catalysts. Such problems can be partly overcome via the introduction of a second transition metal (e.g., Fe, Co) or a noble metal (e.g., Ru, Rh, Pt, Pd and Re) in Ni-based catalysts. Through Ni-M alloy formation, or the intricate synergy between two adjacent metallic phases, new high-performing and low-cost methanation catalysts can be obtained. This review summarizes and critically discusses recent progress made in the field of bimetallic Ni-M (M = Fe, Co, Cu, Ru, Rh, Pt, Pd, Re)-based catalyst development for the CO2 methanation reaction.


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