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1.
Molecular epidemiology, antifungal susceptibility, and ERG11 gene mutation of Candida species isolated from vulvovaginal candidiasis: Comparison between recurrent and non-recurrent infections.
Esfahani, A, Omran, AN, Salehi, Z, Shams-Ghahfarokhi, M, Ghane, M, Eybpoosh, S, Razzaghi-Abyaneh, M
Microbial pathogenesis. 2022;:105696
Abstract
Vulvovaginal candidiasis (VVC) is a prevalent infection of the genitourinary tract affecting millions of women worldwide. In the present study, the importance of virulence factors, ERG11 gene mutations, ERG11 gene expression, and plasma membrane ergosterol content for fluconazole resistance in Candida species was investigated in 200 women suspected of vulvovaginitis. Isolated Candida species were identified using the ITS-restriction fragment length polymorphism (ITS-RFLP) technique. Antifungal susceptibility testing was performed according to the CLSI document. ERG11 gene expression was analyzed using real-time PCR. ERG11 gene mutation analysis was performed using sequencing methods, and the ergosterol content of the cell membrane was determined in fluconazole-resistant isolates. Furthermore, the production of phospholipase and proteinase enzymes was evaluated in recurrent and non-recurrent infections. VVC was diagnosed in 101 (50.5%) of the 200 clinical cases, of which 21 (20.8%) were confirmed as RVVC. Candida albicans was the most prevalent species, followed by C. glabrata, C. tropicalis, C. krusei, C. parapsilosis, and C. guilliermondii. Ketoconazole and fluconazole were the most effective drugs against C. albicans among five tested antifungals with MIC ranges between 0.06 and 16 μg/mL and 0.25-64 μg/mL. Substitutions of A114S, Y257H, T123I and A114V were detected in fluconazole-resistant C. albicans. The ergosterol content of the fungal cell membrane and the mean levels of ERG11 gene expression transcript were higher in fluconazole-resistant C. albicans isolates obtained from RVVC than in those obtained from VVC cases. Phospholipase and proteinase were produced in different amounts in all Candida species isolated from VVC and RVVC cases. In this review, our results demonstrated that several molecular mechanisms, including ERG11 gene expression, changes in the cell membrane ergosterol content, and mutations in ERG11 gene alone or simultaneously involved in fluconazole resistance of C. albicans species and the recurrence of VVC.
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2.
Skin Commensal Fungus Malassezia and Its Lipases.
Park, M, Park, S, Jung, WH
Journal of microbiology and biotechnology. 2021;(5):637-644
Abstract
Malassezia is the most abundant genus in the fungal microflora found on human skin, and it is associated with various skin diseases. Among the 18 different species of Malassezia that have been identified to date, M. restricta and M. globosa are the most predominant fungal species found on human skin. Several studies have suggested a possible link between Malassezia and skin disorders. However, our knowledge on the physiology and pathogenesis of Malassezia in human body is still limited. Malassezia is unable to synthesize fatty acids; hence, it uptakes external fatty acids as a nutrient source for survival, a characteristic compensated by the secretion of lipases and degradation of sebum to produce and uptake external fatty acids. Although it has been reported that the activity of secreted lipases may contribute to pathogenesis of Malassezia, majority of the data were indirect evidences; therefore, enzymes' role in the pathogenesis of Malassezia infections is still largely unknown. This review focuses on the recent advances on Malassezia in the context of an emerging interest for lipases and summarizes the existing knowledge on Malassezia, diseases associated with the fungus, and the role of the reported lipases in its physiology and pathogenesis.
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3.
Investigating the cell and developmental biology of plant infection by the rice blast fungus Magnaporthe oryzae.
Eseola, AB, Ryder, LS, Osés-Ruiz, M, Findlay, K, Yan, X, Cruz-Mireles, N, Molinari, C, Garduño-Rosales, M, Talbot, NJ
Fungal genetics and biology : FG & B. 2021;:103562
Abstract
Magnaporthe oryzae is the causal agent of rice blast disease, the most widespread and serious disease of cultivated rice. Live cell imaging and quantitative 4D image analysis have provided new insight into the mechanisms by which the fungus infects host cells and spreads rapidly in plant tissue. In this video review article, we apply live cell imaging approaches to understanding the cell and developmental biology of rice blast disease. To gain entry to host plants, M. oryzae develops a specialised infection structure called an appressorium, a unicellular dome-shaped cell which generates enormous turgor, translated into mechanical force to rupture the leaf cuticle. Appressorium development is induced by perception of the hydrophobic leaf surface and nutrient deprivation. Cargo-independent autophagy in the three-celled conidium, controlled by cell cycle regulation, is essential for appressorium morphogenesis. Appressorium maturation involves turgor generation and melanin pigment deposition in the appressorial cell wall. Once a threshold of turgor has been reached, this triggers re-polarisation which requires regulated generation of reactive oxygen species, to facilitate septin GTPase-dependent cytoskeletal re-organisation and re-polarisation of the appressorium to form a narrow, rigid penetration peg. Infection of host tissue requires a further morphogenetic transition to a pseudohyphal-type of growth within colonised rice cells. At the same time the fungus secretes an arsenal of effector proteins to suppress plant immunity. Many effectors are secreted into host cells directly, which involves a specific secretory pathway and a specialised structure called the biotrophic interfacial complex. Cell-to-cell spread of the fungus then requires development of a specialised structure, the transpressorium, that is used to traverse pit field sites, allowing the fungus to maintain host cell membrane integrity as new living plant cells are invaded. Thereafter, the fungus rapidly moves through plant tissue and host cells begin to die, as the fungus switches to necrotrophic growth and disease symptoms develop. These morphogenetic transitions are reviewed in the context of live cell imaging studies.
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4.
Exploiting Structural Modelling Tools to Explore Host-Translocated Effector Proteins.
Amoozadeh, S, Johnston, J, Meisrimler, CN
International journal of molecular sciences. 2021;(23)
Abstract
Oomycete and fungal interactions with plants can be neutral, symbiotic or pathogenic with different impact on plant health and fitness. Both fungi and oomycetes can generate so-called effector proteins in order to successfully colonize the host plant. These proteins modify stress pathways, developmental processes and the innate immune system to the microbes' benefit, with a very different outcome for the plant. Investigating the biological and functional roles of effectors during plant-microbe interactions are accessible through bioinformatics and experimental approaches. The next generation protein modeling software RoseTTafold and AlphaFold2 have made significant progress in defining the 3D-structure of proteins by utilizing novel machine-learning algorithms using amino acid sequences as their only input. As these two methods rely on super computers, Google Colabfold alternatives have received significant attention, making the approaches more accessible to users. Here, we focus on current structural biology, sequence motif and domain knowledge of effector proteins from filamentous microbes and discuss the broader use of novel modelling strategies, namely AlphaFold2 and RoseTTafold, in the field of effector biology. Finally, we compare the original programs and their Colab versions to assess current strengths, ease of access, limitations and future applications.
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5.
Coordinated regulation of iron metabolism in Cryptococcus neoformans by GATA and CCAAT transcription factors: connections with virulence.
Jung, WH, Sánchez-León, E, Kronstad, JW
Current genetics. 2021;(4):583-593
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Abstract
Iron acquisition is critical for pathogenic fungi to adapt to and survive within the host environment. However, to same extent, the fungi must also avoid the detrimental effects caused by excess iron. The importance of iron has been demonstrated for the physiology and virulence of major fungal pathogens of humans including Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. In particular, numerous studies have revealed that aspects of iron acquisition, metabolism, and homeostasis in the fungal pathogens are tightly controlled by conserved transcriptional regulators including a GATA-type iron transcription factor and the CCAAT-binding complex (CBC)/HapX orthologous protein complex. However, the specific downstream regulatory networks are slightly different in each fungus. In addition, roles have been proposed or demonstrated for other factors including monothiol glutaredoxins, BolA-like proteins, and Fe-S cluster incorporation on the GATA-type iron transcription factor and the CBC/HapX orthologous protein complex, although limited information is available. Here we focus on recent work on C. neoformans in the context of an emerging framework for fungal regulation of iron acquisition, metabolism, and homeostasis. Our specific goal is to summarize recent findings on transcriptional networks governed by the iron regulators Cir1 and HapX in C. neoformans.
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6.
DyP-Type Peroxidases: Recent Advances and Perspectives.
Sugano, Y, Yoshida, T
International journal of molecular sciences. 2021;(11)
Abstract
In this review, we chart the major milestones in the research progress on the DyP-type peroxidase family over the past decade. Though mainly distributed among bacteria and fungi, this family actually exhibits more widespread diversity. Advanced tertiary structural analyses have revealed common and different features among members of this family. Notably, the catalytic cycle for the peroxidase activity of DyP-type peroxidases appears to be different from that of other ubiquitous heme peroxidases. DyP-type peroxidases have also been reported to possess activities in addition to peroxidase function, including hydrolase or oxidase activity. They also show various cellular distributions, functioning not only inside cells but also outside of cells. Some are also cargo proteins of encapsulin. Unique, noteworthy functions include a key role in life-cycle switching in Streptomyces and the operation of an iron transport system in Staphylococcus aureus, Bacillus subtilis and Escherichia coli. We also present several probable physiological roles of DyP-type peroxidases that reflect the widespread distribution and function of these enzymes. Lignin degradation is the most common function attributed to DyP-type peroxidases, but their activity is not high compared with that of standard lignin-degrading enzymes. From an environmental standpoint, degradation of natural antifungal anthraquinone compounds is a specific focus of DyP-type peroxidase research. Considered in its totality, the DyP-type peroxidase family offers a rich source of diverse and attractive materials for research scientists.
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Regulators of commensal and pathogenic life-styles of an opportunistic fungus-Candida albicans.
Rai, LS, Wijlick, LV, Bougnoux, ME, Bachellier-Bassi, S, d'Enfert, C
Yeast (Chichester, England). 2021;(4):243-250
Abstract
The yeast Candida albicans is primarily a commensal of humans that colonizes the mucosal surfaces of the gastrointestinal and genital tracts. Yet, C. albicans can under certain circumstances undergo a shift from commensalism to pathogenicity. This transition is governed by fungal factors such as morphological transitions, environmental cues for instance relationships with gut microbiota and the host immune system. C. albicans utilizes distinct sets of regulatory programs to colonize or infect its host and to evade the host defense systems. Moreover, an orchestrated iron acquisition mechanism operates to adapt to specific niches with variable iron availability. Studies on regulatory networks and morphogenesis of these two distinct modes of C. albicans growth, suggest that both yeast and hyphal forms exist in both growth patterns and the regulatory circuits are inter-connected. Here, we summarize current knowledge about C. albicans commensal-to-pathogen shift, its regulatory elements and their contribution to human disease.
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8.
Zinc Finger Proteins in the Human Fungal Pathogen Cryptococcus neoformans.
Li, YH, Liu, TB
International journal of molecular sciences. 2020;(4)
Abstract
Zinc is one of the essential trace elements in eukaryotes and it is a critical structural component of a large number of proteins. Zinc finger proteins (ZNFs) are zinc-finger domain-containing proteins stabilized by bound zinc ions and they form the most abundant proteins, serving extraordinarily diverse biological functions. In recent years, many ZNFs have been identified and characterized in the human fungal pathogen Cryptococcus neoformans, a fungal pathogen causing fatal meningitis mainly in immunocompromised individuals. It has been shown that ZNFs play important roles in the morphological development, differentiation, and virulence of C. neoformans. In this review, we, first, briefly introduce the ZNFs and their classification. Then, we explain the identification and classification of the ZNFs in C. neoformans. Next, we focus on the biological role of the ZNFs functionally characterized so far in the sexual reproduction, virulence factor production, ion homeostasis, pathogenesis, and stress resistance in C. neoformans. We also discuss the perspectives on future function studies of ZNFs in C. neoformans.
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Fungal homologues of human Rac1 as emerging players in signal transduction and morphogenesis.
Hühn, J, Musielak, M, Schmitz, HP, Heinisch, JJ
International microbiology : the official journal of the Spanish Society for Microbiology. 2020;(1):43-53
Abstract
A wealth of data is accumulating on the physiological functions of human Rac1, a member of the Rho GTPase family of molecular switches and substrate of botulinum toxin, which was first identified as a regulator of cell motility through its effect on the actin cytoskeleton. Later on, it was found to be involved in different diseases like cancers, cardiac function, neuronal disorders, and apoptotic cell death. Despite the presence of Rac1 homologues in most fungi investigated so far, including Rho5 in the genetically tractable model yeast Saccharomyces cerevisiae, knowledge on their physiological functions is still scarce, let alone the details of the molecular mechanisms of their actions and interactions. Nevertheless, all functions proposed for human Rac1 seem to be conserved in one or the other fungus. This includes the regulation of MAPK cascades, polarized growth, and actin dynamics. Moreover, both the production and response to reactive oxygen species, as well as the reaction to nutrient availability, can be affected. We here summarize the studies performed on fungal Rac1 homologues, with a special focus on S. cerevisiae Rho5, which may be of use in drug development in medicine and agriculture.
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10.
Light in the Fungal World: From Photoreception to Gene Transcription and Beyond.
Corrochano, LM
Annual review of genetics. 2019;:149-170
Abstract
Fungi see light of different colors by using photoreceptors such as the White Collar proteins and cryptochromes for blue light, opsins for green light, and phytochromes for red light. Light regulates fungal development, promotes the accumulation of protective pigments and proteins, and regulates tropic growth. The White Collar complex (WCC) is a photoreceptor and a transcription factor that is responsible for regulating transcription after exposure to blue light. In Neurospora crassa, light promotes the interaction of WCCs and their binding to the promoters to activate transcription. In Aspergillus nidulans, the WCC and the phytochrome interact to coordinate gene transcription and other responses, but the contribution of these photoreceptors to fungal photobiology varies across fungal species. Ultimately, the effect of light on fungal biology is the result of the coordinated transcriptional regulation and activation of signal transduction pathways.