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'Aspergillus' and 'virulence'

Lilian Pereira Silva, Patrícia Alves de Castro, Thaila Fernanda Dos Reis, Mario Henrique Paziani, Márcia Regina Von Zeska Kress, Diego M Riaño-Pachón, Daisuke Hagiwara, Laure N A Ries, Neil Andrew Brown, Gustavo H Goldman
Invasive aspergillosis is predominantly caused by Aspergillus fumigatus and adaptations to stresses experienced within the human host are a prerequisite for the survival and virulence strategies of the pathogen. The central signal transduction pathway operating during hyperosmotic stress is the High Osmolarity Glycerol mitogen-activated protein kinase (MAPK) cascade. A. fumigatus MpkC and SakA, orthologues of the Saccharomyces cerevisiae Hog1p, constitute the primary regulator of the hyperosmotic stress response...
October 5, 2016: Cellular Microbiology
Caitlin H Kowalski, Sarah R Beattie, Kevin K Fuller, Elizabeth A McGurk, Yi-Wei Tang, Tobias M Hohl, Joshua J Obar, Robert A Cramer
UNLABELLED: Previous work has shown that environmental and clinical isolates of Aspergillus fumigatus represent a diverse population that occupies a variety of niches, has extensive genetic diversity, and exhibits virulence heterogeneity in a number of animal models of invasive pulmonary aspergillosis (IPA). However, mechanisms explaining differences in virulence among A. fumigatus isolates remain enigmatic. Here, we report a significant difference in virulence of two common lab strains, CEA10 and AF293, in the murine triamcinolone immunosuppression model of IPA, in which we previously identified severe low oxygen microenvironments surrounding fungal lesions...
September 20, 2016: MBio
Kevin K Fuller, Robert A Cramer, Michael E Zegans, Jay C Dunlap, Jennifer J Loros
UNLABELLED: The given strain of Aspergillus fumigatus under study varies across laboratories, ranging from a few widely used "standards," e.g., Af293 or CEA10, to locally acquired isolates that may be unique to one investigator. Since experiments concerning physiology or gene function are seldom replicated by others, i.e., in a different A. fumigatus background, the extent to which behavioral heterogeneity exists within the species is poorly understood. As a proxy for assessing such intraspecies variability, we analyzed the light response of 15 A...
2016: MBio
Bastian Jöhnk, Özgür Bayram, Anja Abelmann, Thorsten Heinekamp, Derek J Mattern, Axel A Brakhage, Ilse D Jacobsen, Oliver Valerius, Gerhard H Braus
F-box proteins share the F-box domain to connect substrates of E3 SCF ubiquitin RING ligases through the adaptor Skp1/A to Cul1/A scaffolds. F-box protein Fbx15 is part of the general stress response of the human pathogenic mold Aspergillus fumigatus. Oxidative stress induces a transient peak of fbx15 expression, resulting in 3x elevated Fbx15 protein levels. During non-stress conditions Fbx15 is phosphorylated and F-box mediated interaction with SkpA preferentially happens in smaller subpopulations in the cytoplasm...
September 2016: PLoS Pathogens
Falk Hillmann, Karine Bagramyan, Maria Straßburger, Thorsten Heinekamp, Teresa B Hong, Krzysztof P Bzymek, John C Williams, Axel A Brakhage, Markus Kalkum
Invasive aspergillosis and other fungal infections occur in immunocompromised individuals, including patients who received blood-building stem cell transplants, patients with chronic granulomatous disease (CGD), and others. Production of reactive oxygen species (ROS) by immune cells, which incidentally is defective in CGD patients, is considered to be a fundamental process in inflammation and antifungal immune response. Here we show that the peroxiredoxin Asp f3 of Aspergillus fumigatus inactivates ROS. We report the crystal structure and the catalytic mechanism of Asp f3, a two-cysteine type peroxiredoxin...
2016: Scientific Reports
Madhusudan Astekar, Priyanka Sharma Bhatiya, G V Sowmya
BACKGROUND: Although Candida albicans remains the most common cause of human candidiasis, the frequency of infection attributed to other members of the genus is also increasing. Hence, the present study was carried out to know the prevalence of opportunistic candidal infection in tuberculosis, and if positive, the species of Candida that is most commonly associated. MATERIALS AND METHODS: The present study comprised sixty pulmonary tuberculosis patients who were divided into (1) fresh or untreated group, (2A) chronic or treated group having no complications and (2B) having complications, comprising twenty patients each, respectively...
May 2016: Journal of Oral and Maxillofacial Pathology: JOMFP
Mun-Gu Jung, Sung Su Kim, Jae-Hyuk Yu, Kwang-Soo Shin
The G-protein-coupled receptor (GPCR) family represents the largest and most varied collection of membrane embedded proteins that are sensitized by ligand binding and interact with heterotrimeric G proteins. Despite their presumed critical roles in fungal biology, the functions of the GPCR family members in the opportunistic human pathogen Aspergillus fumigatus are largely unknown, as only two (GprC and GprD) of the 15 predicted GPCRs have been studied. Here, we characterize the gprK gene, which is predicted to encode a hybrid GPCR with both 7-transmembrane and regulator of G-protein signaling (RGS) domains...
2016: PloS One
Patrícia Alves de Castro, Thaila Fernanda Dos Reis, Stephen K Dolan, Adriana Oliveira Manfiolli, Neil Andrew Brown, Gary W Jones, Sean Doyle, Diego M Riaño-Pachón, Fábio Márcio Squina, Camila Caldana, Ashutosh Singh, Maurizio Del Poeta, Daisuke Hagiwara, Rafael Silva-Rocha, Gustavo H Goldman
The serine-threonine kinase TOR, the Target of Rapamycin, is an important regulator of nutrient, energy and stress signaling in eukaryotes. Sch9, a Ser/Thr kinase of AGC family (the cAMP-dependent PKA, cGMP- dependent protein kinase G and phospholipid-dependent protein kinase C family), is a substrate of TOR. Here, we characterized the fungal opportunistic pathogen Aspergillus fumigatus Sch9 homologue (SchA). The schA null mutant was sensitive to rapamycin, high concentrations of calcium, hyperosmotic stress and SchA was involved in iron metabolism...
August 19, 2016: Molecular Microbiology
Xingyu Luo, Katharyn J Affeldt, Nancy P Keller
Metabolism of fatty acids is a critical requirement for the pathogenesis of oil seed pathogens including the fungus Aspergillus flavus Previous studies have correlated decreased ability to grow on fatty acids with reduced virulence of this fungus on host seed. Two fatty acid metabolism regulatory transcription factors, FarA and FarB, have been described in other filamentous fungi. Unexpectedly, we find A. flavus possesses three Far homologs, FarA, FarB, and FarC, with FarA and FarC showing a greater protein similarity to each other than FarB...
October 13, 2016: G3: Genes—Genomes—Genetics
Xinyi Nie, Song Yu, Mengguang Qiu, Xiuna Wang, Yu Wang, Youhuang Bai, Feng Zhang, Shihua Wang
Small ubiquitin-like modifiers (SUMOs) can be reversibly attached to target proteins in a process known as SUMOylation, and this process influences several important eukaryotic cell events. However, little is known regarding SUMO or SUMOylation in Aspergillus flavus. Here, we identified a novel member of the SUMO family in A. flavus, AfSumO, and validated the existence of SUMOylation in this pathogenic filamentous fungus. We investigated the roles of AfsumO in A. flavus by determining the effects of AfsumO mutations on the growth phenotype, stress response, conidia and sclerotia production, aflatoxin biosynthesis, and pathogenicity to seeds, and we found that SUMOylation plays a role in fungal virulence and toxin attributes...
September 7, 2016: Journal of Agricultural and Food Chemistry
C M Fernandes, P A de Castro, A Singh, F L Fonseca, M D Pereira, T V M Vila, G C Atella, S Rozental, M Savoldi, M Del Poeta, G H Goldman, E Kurtenbach
C8-desaturated and C9-methylated glucosylceramide (GlcCer) is a fungal-specific sphingolipid that plays an important role in the growth and virulence of many species. In this work, we investigated the contribution of Aspergillus nidulans sphingolipid Δ8-desaturase (SdeA), sphingolipid C9-methyltransferases (SmtA/SmtB) and glucosylceramide synthase (GcsA) to fungal phenotypes, sensitivity to Psd1 defensin and Galleria mellonella virulence. We showed that ΔsdeA accumulated C8-saturated and unmethylated GlcCer, while gcsA deletion impaired GlcCer synthesis...
November 2016: Molecular Microbiology
Marina Campos Rocha, João Henrique Tadini Marilhano Fabri, Krissia Franco de Godoy, Patrícia Alves de Castro, Juliana Issa Hori, Anderson Ferreira da Cunha, Mark Arentshorst, Arthur F J Ram, Cees A M J J van den Hondel, Gustavo Henrique Goldman, Iran Malavazi
The Cell Wall Integrity (CWI) pathway is the primary signaling cascade that controls the de novo synthesis of the fungal cell wall, and in Saccharomyces cerevisiae this event is highly dependent on the RLM1 transcription factor. Here, we investigated the function of RlmA in the fungal pathogen Aspergillus fumigatus We show that the ΔrlmA strain exhibits an altered cell wall organization in addition to defects related to vegetative growth and tolerance to cell wall-perturbing agents. A genetic analysis indicated that rlmA is positioned downstream of the pkcA and mpkA genes in the CWI pathway...
2016: G3: Genes—Genomes—Genetics
José M Vargas-Muñiz, Hilary Renshaw, Amber D Richards, Greg Waitt, Erik J Soderblom, Martin A Moseley, Yohannes Asfaw, Praveen R Juvvadi, William J Steinbach
Septins are a conserved family of GTPases that form hetero-oligomeric complexes and perform diverse functions in higher eukaryotes, excluding plants. Our previous studies in the human fungal pathogen Aspergillus fumigatus revealed that the core septin, AspB, a CDC3 ortholog, is required for septation, conidiation, and conidial cell wall organization. Although AspB is important for these cellular functions, nothing is known about the role of kinases or phosphatases in the posttranslational regulation and localization of septins in A...
2016: Frontiers in Microbiology
Mike Bromley, Anna Johns, Emma Davies, Marcin Fraczek, Jane Mabey Gilsenan, Natalya Kurbatova, Maria Keays, Misha Kapushesky, Marta Gut, Ivo Gut, David W Denning, Paul Bowyer
Recent estimates of the global burden of fungal disease suggest that that their incidence has been drastically underestimated and that mortality may rival that of malaria or tuberculosis. Azoles are the principal class of antifungal drug and the only available oral treatment for fungal disease. Recent occurrence and increase in azole resistance is a major concern worldwide. Known azole resistance mechanisms include over-expression of efflux pumps and mutation of the gene encoding the target protein cyp51a, however, for one of the most important fungal pathogens of humans, Aspergillus fumigatus, much of the observed azole resistance does not appear to involve such mechanisms...
2016: PloS One
Nanbiao Long, Xiaoling Xu, Hui Qian, Shizhu Zhang, Ling Lu
Iron is an essential nutrient and enzyme co-factor required for a wide range of cellular processes, especially for the function of mitochondria. For the opportunistic fungal pathogen Aspergillus fumigatus, the ability to obtain iron is required for growth and virulence during the infection process. However, knowledge of how mitochondria are involved in iron regulation is still limited. Here, we show that a mitochondrial iron transporter, MrsA, a homolog of yeast Mrs4p, is critical for adaptation to iron-limited or iron-excess conditions in A...
2016: Frontiers in Microbiology
Nitin Kumar Singh, Adriana Blachowicz, Aleksandra Checinska, Clay Wang, Kasthuri Venkateswaran
Draft genome sequences of Aspergillus fumigatus strains (ISSFT-021 and IF1SW-F4), opportunistic pathogens isolated from the International Space Station (ISS), were assembled to facilitate investigations of the nature of the virulence characteristics of the ISS strains to other clinical strains isolated on Earth.
2016: Genome Announcements
Paris Laskaris, Ahmad Atrouni, José Antonio Calera, Christophe d'Enfert, Hélène Munier-Lehmann, Jean-Marc Cavaillon, Jean-Paul Latgé, Oumaïma Ibrahim-Granet
Aspergillus fumigatus can infect immunocompromised patients, leading to high mortality rates due to the lack of reliable treatment options. This pathogen requires uptake of zinc from host tissues in order to successfully grow and cause virulence. Reducing the availability of that micronutrient could help treat A. fumigatus infections. In this study, we examined the in vitro effects of seven chelators using a bioluminescent strain of A. fumigatus 1,10-Phenanthroline and N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine (TPEN) proved to be the chelators most effective at inhibiting fungal growth...
October 2016: Antimicrobial Agents and Chemotherapy
Vito Valiante, Clara Baldin, Peter Hortschansky, Radhika Jain, Andreas Thywißen, Maria Straßburger, Ekaterina Shelest, Thorsten Heinekamp, Axel A Brakhage
Melanins play a crucial role in defending organisms against external stressors. In several pathogenic fungi, including the human pathogen Aspergillus fumigatus, melanin production was shown to contribute to virulence. A. fumigatus produces two different types of melanins, i.e., pyomelanin and dihydroxynaphthalene (DHN)-melanin. DHN-melanin forms the gray-green pigment characteristic for conidia, playing an important role in immune evasion of conidia and thus for fungal virulence. The DHN-melanin biosynthesis pathway is encoded by six genes organized in a cluster with the polyketide synthase gene pksP as a core element...
July 9, 2016: Molecular Microbiology
Praveen R Juvvadi, Soo Chan Lee, Joseph Heitman, William J Steinbach
Increases in the incidence and mortality due to the major invasive fungal infections such as aspergillosis, candidiasis and cryptococcosis caused by the species of Aspergillus, Candida and Cryptococcus, are a growing threat to the immunosuppressed patient population. In addition to the limited armamentarium of the current classes of antifungal agents available (pyrimidine analogs, polyenes, azoles, and echinocandins), their toxicity, efficacy and the emergence of resistance are major bottlenecks limiting successful patient outcomes...
June 20, 2016: Virulence
Sourabh Dhingra, Caitlin H Kowlaski, Arsa Thammahong, Sarah R Beattie, Katherine M Bultman, Robert A Cramer
SREBP transcription factors play a critical role in fungal virulence; however, the mechanisms of sterol regulatory element binding protein (SREBP) activation in pathogenic fungi remains ill-defined. Screening of the Neurospora crassa whole-genome deletion collection for genes involved in hypoxia responses identified a gene for an uncharacterized rhomboid protease homolog, rbdB, required for growth under hypoxic conditions. Loss of rbdB in Aspergillus fumigatus also inhibited growth under hypoxic conditions...
March 2016: MSphere
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