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Advances in Aspergillus fumigatus pathobiology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197897 Year: Pages: 109 DOI: 10.3389/978-2-88919-789-7 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Aspergillus fumigatus is a human fungal pathogen that causes invasive aspergillosis (IA), a major infectious cause of death in the expanding population of immunocompromised individuals such as cancer patients and transplant recipients. The mortality of IA remains high (30-70%) and emerging resistance to triazoles, the first-line antifungal drug class, is of particular concern. Second-line therapies for IA are limited by their toxicity (polyenes) or their lack of fungicidal activity (echinocandins). Identification of novel antifungal targets is an urgent need for improving the outcome of IA. A. fumigatus is a filamentous fungus exhibiting a complex developmental cycle and elaborated mechanisms of adaptation to allow the initiation and progression of infection in the human host. The fungal cell wall, with its unique and dynamic structure, is crucial for protecting cell integrity and evading the host immune system, also contributing to biofilm formation and virulence, and thus representing an ideal antifungal target. The emergence of azole resistance implies various and complex mechanisms that need to be further elucidated. Other important processes, such as biosynthetic pathways and toxin/metabolite production are important for fungal survival and propagation in the host environment, ultimately leading to disease. Moreover, the host immune response is a determinant factor in influencing the course of infection. The objective of this topic issue is to provide an overview of the recent advances in our understanding of A. fumigatus pathobiology and of IA pathogenesis to outline future research.

How Can Secretomics Help Unravel the Secrets of Plant-Microbe Interactions?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450879 Year: Pages: 188 DOI: 10.3389/978-2-88945-087-9 Language: English
Publisher: Frontiers Media SA
Subject: Botany --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Secretomics describes the global study of proteins that are secreted by a cell, a tissue or an organism, and has recently emerged as a field for which interest is rapidly growing. The term secretome was first coined at the turn of the millennium and was defined to comprise not only the native secreted proteins released into the extracellular space but also the components of machineries for protein secretion. Two secretory pathways have been described in fungi: i) the canonical pathway through which proteins bearing a N-terminal peptide signal can traverse the endoplasmic reticulum and Golgi apparatus, and ii) the unconventional pathway for proteins lacking a peptide signal. Protein secretion systems are more diverse in bacteria, in which types I to VII pathways as well as Sec or two-arginine (Tat) pathways have been described. In oomycete species, effectors are mostly small proteins containing an N-terminal signal peptide for secretion and additional C-terminal motifs such as RXLRs and CRNs for host targeting. It has recently been shown that oomycetes exploit non-conventional secretion mechanisms to transfer certain proteins to the extracellular environment. Other non-classical secretion systems involved in plant-fugal interaction include extracellular vesicles (EVs, Figure 1 from Samuel et al 2016 Front. Plant Sci. 6:766.). The versatility of oomycetes, fungi and bacteria allows them to associate with plants in many ways depending on whether they are biotroph, hemibiotroph, necrotroph, or saprotroph. When interacting with a live organism, a microbe will invade its plant host and manipulate its metabolisms either detrimentally if it is a pathogen or beneficially if it is a symbiote. Deciphering secretomes became a crucial biological question when an increasing body of evidence indicated that secreted proteins were the main effectors initiating interactions, whether of pathogenic or symbiotic nature, between microbes and their plant hosts. Secretomics may help to contribute to the global food security and to the ecosystem sustainability by addressing issues in i) plant biosecurity, with the design of crops resistant to pathogens, ii) crop yield enhancement, for example driven by arbuscular mycorrhizal fungi helping plant hosts utilise phosphate from the soil hence increase biomass, and iii) renewable energy, through the identification of microbial enzymes able to augment the bio-conversion of plant lignocellulosic materials for the production of second generation biofuels that do not compete with food production. To this day, more than a hundred secretomics studies have been published on all taxa and the number of publications is increasing steadily. Secretory pathways have been described in various species of microbes and/or their plant hosts, yet the functions of proteins secreted outside the cell remain to be fully grasped. This Research Topic aims at discussing how secretomics can assist the scientists in gaining knowledge about the mechanisms underpinning plant-microbe interactions.

Vaccines, Immunotherapy and New Antifungal Therapy Against Fungi: Updates in the New Frontier

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453276 Year: Pages: 183 DOI: 10.3389/978-2-88945-327-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2018-02-27 16:16:45
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Invasive fungal diseases have increased many fold over the past 50 years. Current treatment regimens typically require prolonged administration of antifungal medications that can have significant toxicity. Moreover, our present potent antifungal armamentarium fails to eradicate fungal pathogens from certain compromised hosts. Additionally, invasive fungal diseases continue to have unacceptably high mortality rates. A growing body of work has focused on the utility of vaccines and/or immunotherapy as a powerful tool in combating mycoses, either for the active treatment, as an adjuvant, or in the prevention of specific fungal pathogens. Also, it is growing the interest over new drugs development as second choice for treatment when traditional chemotherapy fail. This Research Topic will detail the exciting progress in developing vaccines, immunotherapy and new drugs for fungi.

The Good, The Bad and The Ugly: Multiple Roles of Bacteria in Human Life

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455744 Year: Pages: 518 DOI: 10.3389/978-2-88945-574-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2019-01-23 14:53:43
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Bacteria are among the earliest forms of life on Earth. Notwithstanding their small size and primitive origin, bacteria still have a tremendous impact on everyday human life. Over the centuries, research into bacteria have provided and enriched the fundamental biological knowledge due to their readily measured processes and effects on higher organisms. Although molecular genetics and microbiology were among the scientific fields that have mostly benefited from the discoveries made in bacteria, our current state of knowledge has gone beyond what anyone could have ever imagined. The present Research Topic aims to cover new and exciting broad aspects of the importance of bacteria to human life, both positive and negative influences. Regulation of bacterial gene expression, replication and segregation control mechanisms, cell to cell communication via quorum sensors, and the relatively recent finding of bacterial immunity via CRISPR, have led to the development of many, and very important new tools in biotechnology and the emerging field of molecular medicine. The battle against infectious diseases has also benefited from the genetic approaches that have been developed in the quest for finding new targets and novel drugs against pathogenic bacteria. At the next level, the human microbiome project has opened up new avenues in understanding the role of bacteria in human health and wellbeing. Finally, the relationship between bacterial infections and human cancers will also be covered, a subject that is still under verification through rigorous experimental approaches. Special emphasis will be given to the bacterial accessory genome, i.e the mobilome, as the primary cause of health-threatening antimicrobial resistance and the production of toxins and virulence factors. Taking into account the evolutionary importance of horizontal gene transfer and the additional beneficial roles of certain bacterial mobile genetic elements, they help project best “the Good, the Bad and the Ugly” outline of this topic.At the time this eBook is about to be published, our Research Topic has registered nearly 55, 000 views.

Emerging Approaches for Typing, Detection, Characterization, and Traceback of Escherichia coli

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451357 Year: Pages: 170 DOI: 10.3389/978-2-88945-135-7 Language: English
Publisher: Frontiers Media SA
Subject: Microbiology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Pathogenic Escherichia coli strains cause a large number of diseases in humans, including diarrhea, hemorrhagic colitis, hemolytic uremic syndrome, urinary tract infections, and neonatal meningitis, while in animals they cause diseases such as calf scours and mastitis in cattle, post-weaning diarrhea and edema disease in pigs, and peritonitis and airsacculitis in chickens. The different E. coli pathotypes are characterized by the presence of specific sets of virulence-related genes. Therefore, it is not surprising that pathogenic E. coli constitutes a genetically heterogeneous family of bacteria, and they are continuing to evolve. Rapid and accurate molecular methods are critically needed to detect and trace pathogenic E. coli in food and animals. They are also needed for epidemiological investigations to enhance food safety, as well as animal and human health and to minimize the size and geographical extent of outbreaks. The serotype of E. coli strains has traditionally been determined using antisera raised against the >180 different O- (somatic) and 53 H- (flagellar) antigens. However, there are many problems associated with serotyping, including: it is labor-intensive and time consuming; cross reactivity of the antisera with different serogroups occurs; antisera are available only in specialized laboratories; and many strains are non-typeable. Molecular serotyping targeting O-group-specific genes within the E. coli O-antigen gene clusters and genes that are involved in encoding for the different flagellar types offers an improved approach for determining the E. coli O- and H-groups. Furthermore, molecular serotyping can be coupled with determination of specific sets of virulence genes carried by the strain offering the possibility to determine O-group, pathotype, and the pathogenic potential simultaneously. Sequencing of the O-antigen gene clusters of all of the known O-groups of E. coli is now complete, and the sequences have been deposited in the GenBank database. The sequence information has revealed that some E. coli serogroups have identical sequences while others have point mutations or insertion sequences and type as different serogroups in serological reactions. There are also a number of other ambiguities in serotyping that need to be resolved. Furthermore, new E. coli O-groups are being identified. Therefore, there is an essential need to resolve these issues and to revise the E. coli serotype nomenclature based on these findings. There are emerging technologies that can potentially be applied for molecular serotyping and detection and characterization of E. coli. On a related topic, the genome sequence of thousands of E. coli strains have been deposited in GenBank, and this information is revealing unique markers such as CRISPR (clustered regularly interspaced short palindromic repeats) and virulence gene markers that could be used to identify E. coli pathotypes. Whole genome sequencing now provides the opportunity to study the role of horizontal gene transfer in the evolution and emergence of pathogenic E. coli strains. Whole genome sequencing approaches are being investigated for genotyping and outbreak investigation for regulatory and public health needs; however, there is a need for establishing bioinformatics pipelines able to handle large amounts of data as we move toward the use of genetic approaches for non-culture-based detection and characterization of E. coli and for outbreak investigations.

Emerging Approaches for Typing, Detection, Characterization, and Traceback of Escherichia coli, 2nd Edition

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454334 Year: Pages: 172 DOI: 10.3389/978-2-88945-433-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2018-11-16 17:17:57
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Pathogenic Escherichia coli strains cause a large number of diseases in humans, including diarrhea, hemorrhagic colitis, hemolytic uremic syndrome, urinary tract infections, and neonatal meningitis, while in animals they cause diseases such as calf scours and mastitis in cattle, post-weaning diarrhea and edema disease in pigs, and peritonitis and airsacculitis in chickens. The different E. coli pathotypes are characterized by the presence of specific sets of virulence-related genes. Therefore, it is not surprising that pathogenic E. coli constitutes a genetically heterogeneous family of bacteria, and they are continuing to evolve. Rapid and accurate molecular methods are critically needed to detect and trace pathogenic E. coli in food and animals. They are also needed for epidemiological investigations to enhance food safety, as well as animal and human health and to minimize the size and geographical extent of outbreaks. The serotype of E. coli strains has traditionally been determined using antisera raised against the >180 different O- (somatic) and 53 H- (flagellar) antigens. However, there are many problems associated with serotyping, including: it is labor-intensive and time consuming; cross reactivity of the antisera with different serogroups occurs; antisera are available only in specialized laboratories; and many strains are non-typeable. Molecular serotyping targeting O-group-specific genes within the E. coli O-antigen gene clusters and genes that are involved in encoding for the different flagellar types offers an improved approach for determining the E. coliO- and H-groups. Furthermore, molecular serotyping can be coupled with determination of specific sets of virulence genes carried by the strain offering the possibility to determine O-group, pathotype, and the pathogenic potential simultaneously. Sequencing of the O-antigen gene clusters of all of the known O-groups of E. coli is now complete, and the sequences have been deposited in the GenBank database. The sequence information has revealed that some E. coli serogroups have identical sequences while others have point mutations or insertion sequences and type as different serogroups in serological reactions. There are also a number of other ambiguities in serotyping that need to be resolved. Furthermore, new E. coli O-groups are being identified. Therefore, there is an essential need to resolve these issues and to revise the E. coli serotype nomenclature based on these findings. There are emerging technologies that can potentially be applied for molecular serotyping and detection and characterization of E. coli. On a related topic, the genome sequence of thousands of E. coli strains have been deposited in GenBank, and this information is revealing unique markers such as CRISPR (clustered regularly interspaced short palindromic repeats) and virulence gene markers that could be used to identify E. coli pathotypes. Whole genome sequencing now provides the opportunity to study the role of horizontal gene transfer in the evolution and emergence of pathogenic E. coli strains. Whole genome sequencing approaches are being investigated for genotyping and outbreak investigation for regulatory and public health needs; however, there is a need for establishing bioinformatics pipelines able to handle large amounts of data as we move toward the use of genetic approaches for non-culture-based detection and characterization of E. coli and for outbreak investigations.

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: eng
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.

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