Journal of Microbiology

EDITORIAL] Human fungal pathogens: Why should we learn?: Jeong-Yoon Kim; J. Microbiol. 2016;54(3):145-148.; DOI: https://doi.org/10.1007/s12275-016-0647-8

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Abstract: Human fungal pathogens that cause invasive infections are hidden killers, taking lives of one and a half million people every year. However, research progress in this field has not been rapid enough to effectively prevent or treat life-threatening fungal diseases. To update recent research progress and promote more active research in the field of human fungal pathogens, eleven review articles concerning the virulence mechanisms and host interactions of four major human fungal pathogens–Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and Histoplasma capsulatum–are presented in this special issue.

REVIEW] Interaction of Candida albicans with host cells: virulence factors, host defense, escape strategies, and the microbiota: Sarah Höfs , Selene Mogavero , Bernhard Hube; J. Microbiol. 2016;54(3):149-169. Published online February 27, 2016; DOI: https://doi.org/10.1007/s12275-016-5514-0

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172 Citations

Abstract: The interaction between Candida albicans and its host cells is characterized by a complex interplay between the expression of fungal virulence factors, which results in adherence, invasion and cell damage, and the host immune system, which responds by secreting proinflammatory cytokines, activating antimicrobial activities and killing the fungal pathogen. In this review we describe this interplay by taking a closer look at how C. albicans pathogenicity is induced and executed, how the host responds in order to prevent and clear an infection, and which mechanisms C. albicans has evolved to bypass these immune responses to avoid clearance. Furthermore, we review studies that show how the presence of other microorganisms affects this interplay.

REVIEW] Hgc1-Cdc28–how much does a single protein kinase do in the regulation of hyphal development in Candida albicans?: Yue Wang; J. Microbiol. 2016;54(3):170-177. Published online February 27, 2016; DOI: https://doi.org/10.1007/s12275-016-5550-9

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19 Citations

Abstract: The fungal human pathogen Candida albicans can cause invasive infection with high mortality rates. A key virulence factor is its ability to switch between three morphologies: yeast, pseudohyphae and hyphae. In contrast to the ovalshaped unicellular yeast cells, hyphae are highly elongated, tube-like, and multicellular. A long-standing question is what coordinates all the cellular machines to construct cells with distinct shapes. Hyphal-specific genes (HSGs) are thought to hold the answer. Among the numerous HSGs found, only UME6 and HGC1 are required for hyphal development. UME6 encodes a transcription factor that regulates many HSGs including HGC1. HGC1 encodes a G1 cyclin which partners with the Cdc28 cyclin-dependent kinase. Hgc1- Cdc28 simultaneously phosphorylates and regulates multiple substrates, thus controlling multiple cellular apparatuses for morphogenesis. This review is focused on major progresses made in the past decade on Hgc1’s roles and regulation in C. albicans hyphal development and other traits important for infection.

REVIEW] Plasma membrane organization promotes virulence of the human fungal pathogen Candida albicans: Lois M. Douglas , James B. Konopka; J. Microbiol. 2016;54(3):178-191. Published online February 27, 2016; DOI: https://doi.org/10.1007/s12275-016-5621-y

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29 Citations

Abstract: Candida albicans is a human fungal pathogen capable of causing lethal systemic infections. The plasma membrane plays key roles in virulence because it not only functions as a protective barrier, it also mediates dynamic functions including secretion of virulence factors, cell wall synthesis, invasive hyphal morphogenesis, endocytosis, and nutrient uptake. Consistent with this functional complexity, the plasma membrane is composed of a wide array of lipids and proteins. These components are organized into distinct domains that will be the topic of this review. Some of the plasma membrane domains that will be described are known to act as scaffolds or barriers to diffusion, such as MCC/eisosomes, septins, and sites of contact with the endoplasmic reticulum. Other zones mediate dynamic processes, including secretion, endocytosis, and a special region at hyphal tips that facilitates rapid growth. The highly organized architecture of the plasma membrane facilitates the coordination of diverse functions and promotes the pathogenesis of C. albicans.

REVIEW] The development of fluconazole resistance in Candida albicans – an example of microevolution of a fungal pathogen: Joachim Morschhäuser; J. Microbiol. 2016;54(3):192-201. Published online February 27, 2016; DOI: https://doi.org/10.1007/s12275-016-5628-4

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Abstract: The yeast Candida albicans is a member of the microbiota in the gastrointestinal and urogenital tracts of most healthy persons, but it can also cause symptomatic infections, especially in immunocompromised patients. During the life-long association with its human host, C. albicans generates genetically altered variants that are better adapted to changes in their environment. A prime example of this microevolution is the development of resistance to the commonly used drug fluconazole, which inhibits ergosterol biosynthesis, during antimycotic therapy. Fluconazole resistance can be caused by mutations in the drug target, by changes in the sterol biosynthesis pathway, and by gain-of-function mutations in transcription factors that result in the constitutive upregulation of ergosterol biosynthesis genes and multidrug efflux pumps. Fluconazole also induces genomic rearrangements that result in gene amplification and loss of heterozygosity for resistance mutations, which further increases drug resistance. These genome alterations may affect extended chromosomal regions and have additional phenotypic consequences. A striking case is the loss of heterozygosity for the mating type locus MTL in many fluconazole-resistant clinical isolates, which allows the cells to switch to the mating-competent opaque phenotype. This, in turn, raises the possibility that sexual recombination between different variants of an originally clonal, drug-susceptible population may contribute to the generation of highly fluconazole-resistant strains with multiple resistance mechanisms. The gain-of-function mutations in transcription factors, which result in deregulated gene expression, also cause reduced fitness. In spite of this, many clinical isolates that contain such mutations do not exhibit fitness defects, indicating that they have overcome the costs of drug resistance with further evolution by still unknown mechanisms.

REVIEW] Innate host defenses against Cryptococcus neoformans: Camaron Hole , Floyd L. Wormley Jr.; J. Microbiol. 2016;54(3):202-211. Published online February 27, 2016; DOI: https://doi.org/10.1007/s12275-016-5625-7

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20 Citations

Abstract: Cryptococcus neoformans, the predominant etiological agent of cryptococcosis, can cause life-threatening infections of the central nervous system in immunocompromised and immunocompetent individuals. Cryptococcal meningoencephalitis is the most common disseminated fungal infection in AIDS patients, and remains the third most common invasive fungal infection among organ transplant recipients. The administration of highly active antiretroviral therapy (HAART) has
result
ed in a decrease in the number of cases of AIDS-related cryptococcosis in developed countries, but in developing countries where HAART is not readily available, Cryptococcus is still a major concern. Therefore, there is an urgent need for the development of novel therapies and/or vaccines to combat cryptococcosis. Understanding the protective immune responses against Cryptococcus is critical for development of vaccines and immunotherapies to combat cryptococcosis. Consequently, this review focuses on our current knowledge of protective immune responses to C. neoformans, with an emphasis on innate immune responses.

REVIEW] All about that fat: Lipid modification of proteins in Cryptococcus neoformans: Felipe H. Santiago-Tirado , Tamara L. Doering; J. Microbiol. 2016;54(3):212-222. Published online February 27, 2016; DOI: https://doi.org/10.1007/s12275-016-5626-6

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10 Citations

Abstract: Lipid modification of proteins is a widespread, essential process whereby fatty acids, cholesterol, isoprenoids, phospholipids, or glycosylphospholipids are attached to polypeptides. These hydrophobic groups may affect protein structure, function, localization, and/or stability; as a consequence such modifications play critical regulatory roles in cellular systems. Recent advances in chemical biology and proteomics have allowed the profiling of modified proteins, enabling dissection of the functional consequences of lipid addition. The enzymes that mediate lipid modification are specific for both the lipid and protein substrates, and are conserved from fungi to humans. In this article we review these enzymes, their substrates, and the processes involved in eukaryotic lipid modification of proteins. We further focus on its occurrence in the fungal pathogen Cryptococcus neoformans, highlighting unique features that are both relevant for the biology of the organism and potentially important in the search for new therapies.

REVIEW] Developmental regulators in Aspergillus fumigatus: Hee-Soo Park , Jae-Hyuk Yu; J. Microbiol. 2016;54(3):223-231. Published online February 27, 2016; DOI: https://doi.org/10.1007/s12275-016-5619-5

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53 Citations

Abstract: The filamentous fungus Aspergillus fumigatus is the most prevalent airborne fungal pathogen causing severe and usually fatal invasive aspergillosis in immunocompromised patients. This fungus produces a large number of small hydrophobic asexual spores called conidia as the primary means of reproduction, cell survival, propagation, and infectivity. The initiation, progression, and completion of asexual development (conidiation) is controlled by various regulators that govern expression of thousands of genes associated with formation of the asexual developmental structure conidiophore, and biogenesis of conidia. In this review, we summarize key regulators that directly or indirectly govern conidiation in this important pathogenic fungus. Better understanding these developmental regulators may provide insights into the improvement in controlling both beneficial and detrimental aspects of various Aspergillus species.

REVIEW] Recent advances in the understanding of the Aspergillus fumigatus cell wall: Mark J. Lee , Donald C. Sheppard; J. Microbiol. 2016;54(3):232-242. Published online February 27, 2016; DOI: https://doi.org/10.1007/s12275-016-6045-4

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60 Citations

Abstract: Over the past several decades, research on the synthesis and organization of the cell wall polysaccharides of Aspergillus fumigatus has expanded our knowledge of this important fungal structure. Besides protecting the fungus from environmental stresses and maintaining structural integrity of the organism, the cell wall is also the primary site for interaction with host tissues during infection. Cell wall polysaccharides are important ligands for the recognition of fungi by the innate immune system and they can mediate potent immunomodulatory effects. The synthesis of cell wall polysaccharides is a complicated process that requires coordinated regulation of many biosynthetic and metabolic pathways. Continuous synthesis and remodeling of the polysaccharides of the cell wall is essential for the survival of the fungus during development, reproduction, colonization and invasion. As these polysaccharides are absent from the human host, these biosynthetic pathways are attractive targets for antifungal development. In this review, we present recent advances in our understanding of Aspergillus fumigatus cell wall polysaccharides, including the emerging role of cell wall polysaccharides in the host-pathogen interaction.

REVIEW] The contribution of Aspergillus fumigatus stress responses to virulence and antifungal resistance: Neil A. Brown , Gustavo H. Goldman; J. Microbiol. 2016;54(3):243-253. Published online February 27, 2016; DOI: https://doi.org/10.1007/s12275-016-5510-4

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56 Citations

Abstract: Invasive aspergillosis has emerged as one of the most common life-threatening fungal disease of humans. The emergence of antifungal resistant pathogens represents a current and increasing threat to society. In turn, new strategies to combat fungal infection are urgently required. Fungal adaptations to stresses experienced within the human host are a prerequisite for the survival and virulence strategies of the pathogen. Here, we review the latest information on the signalling pathways in Aspergillus fumigatus that contribute to stress adaptations and virulence, while highlighting their potential as targets for the development of novel combinational antifungal therapies.

REVIEW] Production of cross-kingdom oxylipins by pathogenic fungi: An update on their role in development and pathogenicity: Gregory J. Fischer , Nancy P. Keller; J. Microbiol. 2016;54(3):254-264. Published online February 27, 2016; DOI: https://doi.org/10.1007/s12275-016-5620-z

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Abstract: Oxylipins are a class of molecules derived from the incorporation of oxygen into polyunsaturated fatty acid substrates through the action of oxygenases. While extensively investigated in the context of mammalian immune responses, over the last decade it has become apparent that oxylipins are a common means of communication among and between plants, animals, and fungi to control development and alter hostmicrobe interactions. In fungi, some oxylipins are derived nonenzymatically while others are produced by lipoxygenases, cyclooxygenases, and monooxygenases with homology to plant and human enzymes. Recent investigations of numerous plant and human fungal pathogens have revealed oxylipins to be involved in the establishment and progression of disease. This review highlights oxylipin production by pathogenic fungi and their role in fungal development and pathogen/ host interactions.

REVIEW] Revisiting old friends: Developments in understanding Histoplasma capsulatum pathogenesis: Jon P. Woods; J. Microbiol. 2016;54(3):265-276. Published online February 27, 2016; DOI: https://doi.org/10.1007/s12275-016-6044-5

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Abstract: Histoplasma capsulatum is a dimorphic pathogenic fungus and causative agent of histoplasmosis, which is a respiratory and systemic infection that is particularly severe in immunocompromised hosts and represents the fungal homolog of tuberculosis. In highly endemic regions, the majority of individuals have been infected and carry the organism in a persistent latent form that is a danger for reactivation if host defenses are suppressed. H. capsulatum has been a model organism for intracellular pathogenesis and fungal morphogenesis for decades. New genomic information and application of approaches for molecular genetic manipulation are shedding new light on virulence mechanisms.

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