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Antifungal Drug Discovery: New Theories and New Therapies

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199501 Year: Pages: 136 DOI: 10.3389/978-2-88919-950-1 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Fungal infections such as candidoses can range from superficial mucous membrane infection to life-threatening systemic mycoses. Candida infections are a significant clinical problem globally due to rapid rise in compromised host populations including HIV/AIDS, organ transplant recipients and patients on chemotherapy. In addition, sharp increase in aging populations which are susceptible to fungal infections is expected in next few decades. Antifungal drugs are relatively difficult to develop compared to the antibacterial drugs owing to the eukaryotic nature of the cells. Therefore, only a handful of antifungal agents are currently available to treat the myriad of fungal infections. Moreover, rising antifungal resistance and host-related adverse reactions have limited the antifungal arsenal against fungal pathogens. In this research topic, we tried to update the theoretical aspects pertaining to the antifungal drug discovery i.e. proposed novel mechanisms, new drug targets and pathways. In addition, invited authors explored the new antifungal drugs derived from natural and synthetic sources which are currently under development. Contributors were encouraged to bring new insight into the antifungal drug discovery. We hope the reader may arrive at a general consensus on the possible strategies to combat ever increasing ubiquitous fungal infection in this new century.

Recent Advances in the Study of the Host-Fungus Interaction

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450626 Year: Pages: 148 DOI: 10.3389/978-2-88945-062-6 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Fungal infections represent nowadays a significant burden on the healthcare system of most of the countries, and are among the infections with the highest mortality rates. This has fostered the study of the interaction of these organisms with the human host. The outer most layer of a fungal cell is the cell wall, and together with the secreted components into the extracellular compartment, are the first lines of contact with the host cells. This interaction is critical for tissue adhesion, colonization and damage. In addition, these fungal extracellular components will define the outcome of the interaction with the host immune cells, leading either to the establishment of a protective antifungal immune response or to an immune-evasive mechanism by the fungal cell. On the other hand, our immune system has effectively evolved to deal with fungal pathogens, developing strategies for cell eradication, burden control, or antigen presentation from the innate branch to the adaptive immune response. Here, we provide a series of comprehensive review papers dealing with both aspect of the interaction fungus-immune cells: the role of virulence factors and cell wall components during such interaction, and the recent advances in the study of cellular receptors in the establishment of a protective anti-fungal immune response.

The Neonatal Immune System: A Unique Host-Microbial Interface

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454037 Year: Pages: 175 DOI: 10.3389/978-2-88945-403-7 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Pediatrics --- Allergy and Immunology --- Science (General) --- Microbiology
Added to DOAB on : 2018-11-16 17:17:57
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Emerging from the protective environment of the uterus, the newborn is exposed to a myriad of microbes, and quickly establishes a complex microbiome that shapes the infant’s biology in ways that are only now beginning to come to light. Among these exposures are a number of potential pathogens. The host responses to these pathogens in the neonatal period are unique, reflecting a developing immune system even with delivery at term. Preterm infants are delivered at a time when host defense mechanisms are even less developed and therefore face additional risk. As such, the organisms that cause disease in this period are different from the pathogens that are common in other age groups, or the disease they cause manifests in more severe fashion. Developmental alterations in both innate and adaptive immune responses in neonates have been documented among many cell types and pathways over the last several decades. Contemporary insights into the human immune system and methodologies that allow an “omics” approach to these questions have continued to provide new information regarding the mechanisms that underlie the human neonate as an “immunocompromised host.” This Research Topic highlights studies related to this unique host-pathogen interface. Contributions include those related to the innate or adaptive immune system of neonates, their response to microbial colonization or infection, and/or the pathogenesis of microbes causing disease in neonates.

The Evolving Telomeres

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198818 Year: Pages: 74 DOI: 10.3389/978-2-88919-881-8 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
Added to DOAB on : 2016-01-19 14:05:46
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What controls the different rates of evolution to give rise to conserved and divergent proteins and RNAs? How many trials until evolution can adapt to physiological changes? Every organism has arisen through multiple molecular changes, and the mechanisms that are employed (mutagenesis, recombination, transposition) have been an issue left to the elegant discipline of evolutionary biology. But behind the theory are realities that we have yet to ascertain: How does an evolving cell accommodate its requirements for both conserving its essential functions, while also providing a selective advantage? In this volume, we focus on the evolution of the eukaryotic telomere, the ribo-nuclear protein complex at the end of a linear chromosome. The telomere is an example of a single chromosomal element that must function to maintain genomic stability. The telomeres of all species must provide a means to avoid the attrition from semi-conservative DNA replication and a means of telomere elongation (the telomere replication problem). For example, telomerase is the most well-studied mechanism to circumvent telomere attrition by adding the short repeats that constitutes most telomeres. The telomere must also guard against the multiple activities that can act on an unprotected double strand break requiring a window (or checkpoint) to compensate for telomere sequence loss as well as protection against non-specific processes (the telomere protection problem). This volume describes a range of methodologies including mechanistic studies, phylogenetic comparisons and data-based theoretical approaches to study telomere evolution over a broad spectrum of organisms that includes plants, animals and fungi. In telomeres that are elongated by telomerases, different components have widely different rates of evolution. Telomerases evolved from roots in archaebacteria including splicing factors and LTR-transposition. At the conserved level, the telomere is a rebel among double strand breaks (DSBs) and has altered the function of the highly conserved proteins of the ATM pathway into an elegant means of protecting the chromosome end and maintaining telomere size homeostasis through a competition of positive and negative factors. This homeostasis, coupled with highly conserved capping proteins, is sufficient for protection. However, far more proteins are present at the telomere to provide additional species-specific functions. Do these proteins provide insight into how the cell allows for rapid change without self-destruction?

Fungal Pathogenesis in Humans: The Growing Threat

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ISBN: 9783038979005 9783038979012 Year: Pages: 232 DOI: 10.3390/books978-3-03897-901-2 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Genetics
Added to DOAB on : 2019-06-26 08:44:06
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Cancer survival rates and successful organ transplantation in patients continues to increase due to improvements in early diagnosis and treatments. Since immuno-suppressive therapies are frequently used, the mortality rate due to secondary infections has become an ever-increasing problem. Opportunistic fungal infections are probably the deadliest threat to these patients due to their difficult early diagnosis, the limited effect of antifungal drugs and the appearance of resistances. In recent years, a considerable effort has been devoted to investigating the role of many virulence traits in the pathogenic outcome of fungal infections. New virulence factors (hypoxia adaptation, CO2 sensing, pH regulation, micronutrient acquisition, secondary metabolites, immunity regulators, etc.) have been reported and their molecular mechanisms of action are being thoroughly investigated. The recent application of gene-editing technologies such as CRISPr-Cas9, has opened a whole new window to the discovery of new fungal virulence factors. Accurate fungal genotyping, Next Generation Sequencing and RNAseq approaches will undoubtedly provide new clues to interpret the plethora of molecular interactions controlling these complex systems. Unraveling their intimate regulatory details will provide insights for a more target-focused search or a rational design of more specific antifungal agents. This Special Issue is show significant discoveries, proofs of concept of new theories or relevant observations in fungal pathogenesis and its regulation.

Fungal Infections in Immunocompromised Hosts

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ISBN: 9783038977162 Year: Pages: 212 DOI: 10.3390/books978-3-03897-717-9 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Microbiology --- Biology --- Science (General)
Added to DOAB on : 2019-04-05 10:34:31
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This book is a printed edition of the Special Issue Fungal Infections in Immunocompromised Hosts that was published in JoF

Keywords

Candida auris --- Aspergillus fumigatus --- antifungal resistance --- multidrug resistance --- mechanisms of antifungal resistance --- liver disease --- hepatic impairment --- invasive fungal infection --- antifungal agent --- antifungal drug --- toxicity --- Immunotherapy --- invasive aspergillosis --- Aspergillus fumigatus --- fungal infections --- innate immunity --- adaptive immunity --- cell therapy --- cytokine therapy --- taxonomy --- fungal nomenclature --- phylogenetics --- species complex --- invasive fungal infections --- mycoses --- immune reconstitution inflammatory syndrome --- fungal immunity --- prognostic risk model --- prediction models --- risk score --- invasive mold disease --- hematological malignancy --- risk assessment --- antifungal stewardship --- paracoccidioidomycosis --- HIV --- cancer --- lymphoma --- kidney transplant --- TNF inhibitors --- literature review --- MALDI-ToF MS --- yeast --- fungus --- AIDS --- IRIS --- cat-transmitted sporotrichosis --- immunocompromised hosts --- mycoses of implantation --- sporotrichosis --- Sporothrix brasiliensis --- Sporothrix schenckii --- subcutaneous mycoses --- invasive fungal infection --- non-culture-based diagnostics --- aspergillosis --- candidiasis --- Aspergillus PCR --- galactomannan --- lateral flow --- beta-d-glucan --- T2 Candida --- candidemia --- Candida meningoencephalitis --- (1?3)-?-d-glucan --- T2Candida --- PCR --- liposomal amphotericin B --- micafungin --- anidulafungin --- Aspergillus --- anti-fungal agents --- hematological malignancies

Enological Repercussions of Non-Saccharomyces Species

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ISBN: 9783039215584 9783039215591 Year: Pages: 218 DOI: 10.3390/books978-3-03921-559-1 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:16
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From the beginning of this century, non-Saccharomyces yeasts have taken increased relevance in wine processing. Several biotechnological companies now produce non-Saccharomyces yeasts at an industrial level to improve aroma or flavor, stabilize wine, produce biological acidification, or conversely metabolize malic acid. Species like Torulaspora delbrueckii, Metschnikowia pulcherrima, Kloeckera apiculata, Lachancea thermotolerans, Schizosaccharomyces pombe, and several others are common due to the technological applications they have in sensory quality but also in wine ageing and stabilization. Moreover, spoilage non-Saccharomyces yeasts like Brettanomyces bruxellensis, Saccharomycodes ludwigii, and Zygosacharomyces bailii are becoming important because of the alterations they are able to produce in high-quality wines. New strategies to control these defective yeasts have been developed to control them without affecting sensory quality. The knowledge of the physiology, ecology, biochemistry, and metabolomics of these yeasts can help to better use them in controlling traditional problems such as low fermentative power, excessive volatile acidity, low implantation under enological conditions, and sensibility to antimicrobial compounds like sulfites traditionally used in wine processing. This Special Issue intends to compile current research and revised information on non-Saccharomyces yeasts with enological applications to facilitate the use and the understanding of this biotechnological tool. In 1 year this SI has globally more than 15kdownloads and produced more than 30 citations.

Keywords

Lachancea thermotolerans --- Kluyveromyces thermotolerans --- acidification --- wines --- sequential fermentations --- non-Saccharomyces --- non-Saccharomyces yeasts --- Wickerhamomyces anomalus --- Pichia anomala --- enzymes --- glycosidases --- acetate esters --- biocontrol --- mixed starters --- wine --- wine --- Zygosaccharomyces rouxii --- re-fermentation --- spoilage-control --- non-Saccharomyces --- high-ethanol --- Schizosaccharomyces pombe --- oenological uses --- maloalcoholic fermentation --- stable pigments --- wine safety --- non-Saccharomyces yeast --- Saccharomycodes ludwigii --- S. ludwigii --- spoilage yeasts’ control --- ageing-on-lees --- non-Saccharomyces --- yeast --- sparkling wine --- nitrogen --- aroma --- Candida stellata --- ecology --- taxonomy --- metabolism --- processing foods --- co-fermentation --- non-Saccharomyces --- genome --- aroma compounds --- anthocyanin --- mixed cultures fermentation --- flavor complexity --- Aureobasidium pullulans --- biotechnological applications --- viticulture --- enzymes --- non-Saccharomyces yeasts --- Torulaspora delbrueckii --- winemaking --- yeast inoculation --- yeast dominance --- wine quality --- genetic improvement --- antimicrobial peptides --- biocontrol --- Brettanomyces bruxellensis --- Candida intermedia --- wine --- off-flavors --- wine acidity --- volatile acidity --- malolactic bacteria --- Lactobacillus plantarum --- Lachancea thermotolerans --- Schizosaccharomyces pombe --- Candida stellate --- Torulaspora delbrueckii --- Zygotorulaspora florentina --- Pichia kudriavzevii --- Stermerella bacillaris --- Metschnikowia pulcherrima --- oenological uses --- enzymes --- stable pigments --- pulcherrimin --- n/a --- n/a

Microbial Biofilms in Healthcare: Formation, Prevention and Treatment

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ISBN: 9783039284108 9783039284115 Year: Pages: 166 DOI: 10.3390/books978-3-03928-411-5 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Microbiology
Added to DOAB on : 2020-04-07 23:07:09
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Biofilms are ubiquitous and their presence in industry can lead to production losses. However, nowhere do biofilms impact human health and welfare as much as those that are found contaminating the healthcare environment, surgical instruments, equipment, and medical implantable devices. Approximately 70% of healthcare-associated infections are due to biofilm formation, resulting in increased patient morbidity and mortality. Biofilms formed on medical implants are recalcitrant to antibiotic treatment, which leaves implant removal as the principal treatment option. In this book, we investigate the role of biofilms in breast and dental implant disease and cancer. We include in vitro models for investigating treatment of chronic wounds and disinfectant action against Candida sp. Also included are papers on the most recent strategies for treating biofilm infection ranging from antibiotics incorporated into bone void fillers to antimicrobial peptides and quorum sensing.

The Interplay of Microbiome and Immune Response in Health and Diseases

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ISBN: 9783039216468 9783039216475 Year: Pages: 206 DOI: 10.3390/books978-3-03921-647-5 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Internal medicine
Added to DOAB on : 2019-12-09 11:49:16
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[Increasing evidence suggests that microbiota and especially the gut microbiota (the microbes inhabiting the gut including bacteria, archaea, viruses, and fungi) plays a key role in human physiology and pathology. Recent findings indicate how dysbiosis—an imbalance in the composition and organization of microbial populations—could severely impact the development of different medical conditions (from metabolic to mood disorders), providing new insights into the comprehension of diverse diseases, such as IBD, obesity, asthma, autism, stroke, diabetes, and cancer. Given that microbial cells in the gut outnumber host cells, microbiota influences human physiology both functionally and structurally. Microbial metabolites bridge various—even distant—areas of the organism by way of the immune and hormone system. For instance, it is now clear that the mutual interaction between the gastrointestinal tract and the brain (gut–brain axis), often involves gut microbiota, indicating that the crosstalk between the organism and its microbial residents represents a fundamental aspect of both the establishment and maintenance of healthy conditions. Moreover, it is crucial to recognize that beyond the intestinal tract, microbiota populates other host organs and tissues (e.g., skin and oral mucosa). We have edited this eBook with the aim of publishing manuscripts focusing on the impact of microbiota in the development of different diseases and their associated treatments.]

Keywords

microbiota --- rheumatoid arthritis --- anti-TNF-? --- methotrexate --- etanercept --- disease activity --- microbiome --- health --- precision medicine --- genomics --- bacteriocins --- bacteriophages --- antibiotics --- gastrointestinal diseases --- dysbiosis --- gut barrier --- gut microbiota --- virus --- vaginal microbiota --- HIV --- HPV --- HSV2 --- cytokines --- chemokines --- innate immunity --- adaptive immunity --- microbiota --- autoimmunity --- etiopathogenesis --- Candida albicans --- 2,3-dihydroxy-4-methoxyBenzaldehyde --- melanin --- colitis --- anaerobic bacteria --- aerobic bacteria --- gut microbiota --- gut-liver axis --- chronic liver diseases --- fecal transplantation --- probiotics --- gut microbiota --- immunological niche --- dysbiosis --- cancer --- immune system --- cutaneous immunity --- microbiome --- Staphylococcus spp., T cells --- Staphylococcus aureus --- Staphylococcus epidermis --- commensals --- atopic dermatitis --- intravenous immunoglobulin G --- colitis --- dextran sulfate sodium --- mice --- inflammation --- cytokines --- Candida albicans --- Escherichia coli --- Enterococcus faecalis --- gut microbiota --- chemo free treatment --- lymphoid malignancies --- 16S rRNA gene --- chondroitin sulfate disaccharide --- co-occurrence network --- global network --- microbial interactions --- microbiome --- modularity --- superoxide dismutase --- gut microbiota --- macrophages --- TLR mimicry --- immune epigenetics --- metabolism --- sterile inflammation --- microbiota --- microbiome --- immunotherapy --- adoptive cell transfer (ACT) --- CAR T-cell --- TCR --- TIL --- checkpoint inhibitors --- immuno-oncology --- cancer --- diet --- n/a

Thermophiles and Thermozymes

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ISBN: 9783038978169 9783038978176 Year: Pages: 198 DOI: 10.3390/books978-3-03897-817-6 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General)
Added to DOAB on : 2019-04-25 16:37:17
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Interest in the study of life in hot environments, both with respect to the inhabiting microorganisms and the enzymes they produce, is currently very high. The biological mechanisms responsible for the resistance to high temperatures are not yet fully understood, whereas thermostability is a highly required feature for industrial applications. In this e-book, the invited authors provide diverse evidence contributing to the understanding of such mechanisms and the unlocking of the biotechnological potential of thermophiles and thermozymes.

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