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Cryptococcus neoformans

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https://www.readbyqxmd.com/read/27918582/investigating-conservation-of-the-cell-cycle-regulated-transcriptional-program-in-the-fungal-pathogen-cryptococcus-neoformans
#1
Christina M Kelliher, Adam R Leman, Crystal S Sierra, Steven B Haase
The pathogenic yeast Cryptococcus neoformans causes fungal meningitis in immune-compromised patients. Cell proliferation in the budding yeast form is required for C. neoformans to infect human hosts, and virulence factors such as capsule formation and melanin production are affected by cell-cycle perturbation. Thus, understanding cell-cycle regulation is critical for a full understanding of virulence factors for disease. Our group and others have demonstrated that a large fraction of genes in Saccharomyces cerevisiae is expressed periodically during the cell cycle, and that proper regulation of this transcriptional program is important for proper cell division...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27917162/activity-of-scorpion-venom-derived-antifungal-peptides-against-planktonic-cells-of-candida-spp-and-cryptococcus-neoformans-and-candida-albicans-biofilms
#2
Fernanda Guilhelmelli, Nathália Vilela, Karina S Smidt, Marco A de Oliveira, Alice da Cunha Morales Álvares, Maria C L Rigonatto, Pedro H da Silva Costa, Aldo H Tavares, Sônia M de Freitas, André M Nicola, Octávio L Franco, Lorena da Silveira Derengowski, Elisabeth F Schwartz, Márcia R Mortari, Anamélia L Bocca, Patrícia Albuquerque, Ildinete Silva-Pereira
The incidence of fungal infections has been increasing in the last decades, while the number of available antifungal classes remains the same. The natural and acquired resistance of some fungal species to available therapies, associated with the high toxicity of these drugs on the present scenario and makes an imperative of the search for new, more efficient and less toxic therapeutic choices. Antimicrobial peptides (AMPs) are a potential class of antimicrobial drugs consisting of evolutionarily conserved multifunctional molecules with both microbicidal and immunomodulatory properties being part of the innate immune response of diverse organisms...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27915049/csn1201-a-subunit-of-the-cop9-signalosome-regulates-the-virulence-in-cryptococcus-neoformans-infection
#3
Yibin Fan, Xiaohua Tao, Weili Pan, Wei Fang, Youming Huang, Mingyan Jia
The COP9 signalosome (CSN) is a multisubunit protein complex, and it now has been found to participate in diverse cellular and developmental processes in various eukaryotic organisms. Cryptococcus neoformans (C. neoformans) is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily in the immune compromised population. Here, we generated CSN deletion mutants to investigate the role in Cryptococcus infection. Compared to other CSN mutants, we identified a CSN1201 mutant exhibited severely attenuated virulence...
November 30, 2016: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/27909750/repression-of-proteases-and-hsp90-chaperone-expression-induced-by-an-antiretroviral-in-virulent-environmental-strains-of-cryptococcus-neoformans
#4
Cleber Fernando Serafin, Ana Paula Paris, Claudete Rodrigues Paula, Rita Cássia Garcia Simão, Rinaldo Ferreira Gandra
This study evaluated the effect of the antiretroviral ritonavir on protease secretion in different strains of Cryptococcus neoformans isolated from the environment and investigated the expression of heat shock protein (Hsp90), classically described virulence factors in other yeast in the presence of the same antiretroviral. The presence of the enzyme was detected by the formation of a degradation of the halo around the colonies. The results were classified as follows: level 1 (without proteases), level 2 (positive for proteases), and level 3 (strongly positive for proteases)...
December 2, 2016: Microbial Ecology
https://www.readbyqxmd.com/read/27905163/fungal-glycolipid-hydrolase-inhibitors-and-their-effect-on-cryptococcus-neoformans
#5
Andres Gonzalez Santana, Christina Tysoe, Guanggan Hu, James Kronstad, Ethan Goddard-Borger, Stephen Withers
Pathogenic fungi kill an estimated 1.3 million people each year. This number is predicted to rise as drug resistance spreads, thus antifungal drugs with novel modes of action are urgently required. Fungal endoglycoceramidase-related proteins 1 and 2 (EGCrP-1 and -2), which hydrolyse glucosylceramide and ergosteryl beta-glucoside, respectively, are important for fungal cell growth and have been identified as potential targets for drug development. A library of iminosugar derivatives was screened against EGCrP-1 and -2, thereby identifying a number of competitive inhibitors with nanomolar affinities...
November 30, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27904878/de-novo-pyrimidine-biosynthesis-connects-cell-integrity-to-amphotericin-b-susceptibility-in-cryptococcus-neoformans
#6
Dithi Banerjee, Timothy C Umland, John C Panepinto
The use of amphotericin B (AmB) in conjunction with 5-fluorocytosine (5-FC) is known to be the optimal therapy for treating cryptococcosis, but the mechanism by which 5-FC synergizes with AmB is unknown. In this study, we generated a Cryptococcus neoformans ura1Δ mutant lacking dihydroorotate dehydrogenase (DHODH), which demonstrated temperature-sensitive growth due to a defect in cell integrity and sensitivity to cell wall-damaging agents. In addition, sensitivity to AmB was greatly increased. Inclusion of uracil or uridine in the medium did not suppress the cell wall or AmB phenotype, whereas complementation with the wild-type URA1 gene complemented the mutant phenotype...
November 2016: MSphere
https://www.readbyqxmd.com/read/27903420/microbiology-of-processed-edible-insect-products-results-of-a-preliminary-survey
#7
Nils Th Grabowski, Günter Klein
Little is known of the microbiology of processed insect products. The present survey analysed a total of n=38 samples of deep-fried and spiced (Acheta domesticus, Locusta migratoria, and Omphisa fuscidentalis), cooked in soy sauce ("tsukudani"; Oxya yezoensis, Vespula flaviceps, and Bombyx mori), dried (A. domesticus, L. migatoria, Alphitobius diaperinus, Tenebrio molitor, B. mori, Hermetia illucens, and Musca domestica), powdered (H. illucens, T. molitor) and other (incl. deep-frozen B. mori and honeybee pollen) insect products microbiologically (total bacterial count [TBC], Enterobacteriaceae, staphylococci, bacilli, and yeasts and moulds counts, salmonellae, Listeria monocytogenes, and Escherichia coli)...
November 9, 2016: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/27899501/unraveling-fungal-radiation-resistance-regulatory-networks-through-the-genome-wide-transcriptome-and-genetic-analyses-of-cryptococcus-neoformans
#8
Kwang-Woo Jung, Dong-Hoon Yang, Min-Kyu Kim, Ho Seong Seo, Sangyong Lim, Yong-Sun Bahn
The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation...
November 29, 2016: MBio
https://www.readbyqxmd.com/read/27891372/experience-with-splenic-abscess-from-southern-india
#9
Mallikarjuna Shetty, Swaroopa Deme, Knkj Mohan, Krishna Prasad Adiraju, Nageswar Rao Modugu, Naval Chandra, Amvr Narendra, Sathyanarayana Raju Yadati
INTRODUCTION: Splenic abscess is a rare entity with potentially life threatening complications. Sparse recent published data are available documenting the aetiological profile and management of patients with splenic abscess from India. AIM: To study the clinical profile of splenic abscess. MATERIALS AND METHODS: We retrospectively collected data from case records of admitted patients with splenic abscesses, to Nizam's Institute of Medical Sciences and Hospital which is a multispecialty, tertiary care referral hospital over a period of 15 months (from March 2014 to May 2015) and parameters studied were age, sex, symptoms, signs, risk factors, investigations like Ultrasound, CT scan, blood & microbiological culture, treatment and outcome...
October 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27890876/synthesis-and-antifungal-in-vitro-evaluation-of-pyrazolo-3-4-b-pyridines-derivatives-obtained-by-aza-diels-alder-reaction-and-microwave-irradiation
#10
Jairo Quiroga, Yazmín Villareal, Jaime Gálvez, Alejandro Ortíz, Braulio Insuasty, Rodrigo Abonia, Marcela Raimondi, Susana Zacchino
A series of pyrazolo[3,4-b]pyridines were prepared by a microwawe-assisted aza-Diels-Alder reaction between pyrazolylformimidamides 1 and β-nitrostyrenes 2 in toluene as the solvent. This procedure provides a simple one-step and environmentally friendly methodology with good yields for the synthesis of these compounds. All compounds were tested for antifungal activity against two clinically important fungi Candida albicans and Cryptococcus neoformans. Within the compounds of the series bearing a -CH3 group on the carbon C-3 of the azole ring (3a-3e), the compound without a substituent on the p'-phenyl ring (3a), showed the best activity against both fungi, followed by the p'-Br-phenyl (3c)...
November 25, 2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27876784/expression-and-characterization-of-a-talaromyces-marneffei-active-phospholipase-b-expressed-in-a-pichia-pastoris-expression-system
#11
Yan He, Linghua Li, Fengyu Hu, Wanshan Chen, Huali Lei, Xiejie Chen, Weiping Cai, Xiaoping Tang
Phospholipase B is a virulence factor for several clinically important pathogenic fungi, including Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus, but its role in the thermally dimorphic fungus Talaromyces marneffei remains unclear. Here, we provide the first report of the expression of a novel phospholipase gene, designated TmPlb1, from T. marneffei in the eukaryotic expression system of Pichia pastoris GS115. Sensitive real-time quantitative reverse-transcription PCR (qRT-PCR) demonstrated that the expression of TmPlb1 increased 1...
November 23, 2016: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/27872188/a-monoclonal-antibody-to-cryptococcus-neoformans-glucuronoxylomannan-manifests-hydrolytic-activity-for-both-peptides-and-polysaccharides
#12
Anthony Bowen, Maggie P Wear, Radames Cordero, Stefan Oscarson, Arturo Casadevall
Studies in the 1980s first showed that some natural antibodies were "catalytic" and able to hydrolyze peptide or phosphodiester bonds in antigens. Many naturally occurring catalytic antibodies have since been isolated from human sera and associated with positive and negative outcomes in autoimmune disease and infection. The function and prevalence of these antibodies, however, remains unclear. A previous study suggested that the 18B7 monoclonal antibody against glucuronoxylomannan (GXM)--the major component of the Cryptococcus neoformans polysaccharide capsule--hydrolyzed a peptide antigen mimetic...
November 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27866353/nimesulide-inhibits-pathogenic-fungi-pge2-dependent-mechanisms
#13
Rafaelle Fonseca de Matos, Lúcia Carla Vasconcelos Mendonça, Kaira Geiliane da Silva Souza, Adriana Aparecida Durães Fonseca, Elaine Mirla Souza Costa, Marcus Vinicius Dias de Lima, José Maria Dos Santos Vieira, Mioni Thielli Figueiredo Magalhães de Brito, Marta Chagas Monteiro
Certain non-steroidal anti-inflammatory drugs can inhibit fungal growth, fungal prostaglandin E2 production, and enzyme activation. This study aims to investigate the antifungal effect of nimesulide against pathogenic filamentous fungi and yeast. The experiments detailed below were also designed to investigate whether the action is dependent on E2 fungal prostaglandins. Our data showed that nimesulide exhibited potent antifungal activity, mainly against Trichophyton mentagrophytes (ATCC 9533) and Cryptococcus neoformans with MIC values of 2 and 62 μg/mL, respectively...
November 19, 2016: Folia Microbiologica
https://www.readbyqxmd.com/read/27866167/rewiring-of-signaling-networks-modulating-thermotolerance-in-the-human-pathogen-cryptococcus-neoformans
#14
Dong-Hoon Yang, Kwang-Woo Jung, Soohyun Bang, Jang-Won Lee, Min-Hee Song, Anna Floyd-Averette, Richard A Festa, Giuseppe Ianiri, Alexander Idnurm, Dennis J Thiele, Joseph Heitman, Yong-Sun Bahn
Thermotolerance is a crucial virulence attribute for human pathogens, including the fungus Cryptococcus neoformans that causes fatal meningitis in humans. Loss of the protein kinase Sch9 increases C. neoformans thermotolerance, but its regulatory mechanism has remained unknown. Here, we studied the Sch9-dependent and Sch9-independent signaling networks modulating C. neoformans thermotolerance by using genome-wide transcriptome analysis and reverse genetic approaches. During temperature upshift, genes encoding for molecular chaperones and heat shock proteins were upregulated, whereas those for translation, transcription, and sterol biosynthesis were highly suppressed...
November 18, 2016: Genetics
https://www.readbyqxmd.com/read/27864424/erratum-for-voelz-et-al-cytokine-signaling-regulates-the-outcome-of-intracellular-macrophage-parasitism-by-cryptococcus-neoformans
#15
Kerstin Voelz, David A Lammas, Robin C May
No abstract text is available yet for this article.
December 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27862555/genomic-epidemiology-of-cryptococcus-yeasts-identifies-adaptation-to-environmental-niches-underpinning-infection-across-an-african-hiv-aids-cohort
#16
Mathieu Vanhove, Mathew A Beale, Johanna Rhodes, Duncan Chanda, Shabir Lakhi, Geoffrey Kwenda, Sile Molloy, Natasha Karunaharan, Neil Stone, Thomas S Harrison, Tihana Bicanic, Matthew C Fisher
Emerging infections caused by fungi have become a widely recognized global phenomenon and are causing an increasing burden of disease. Genomic techniques are providing new insights into the structure of fungal populations, revealing hitherto undescribed fine-scale adaptations to environments and hosts that govern their emergence as infections. Cryptococcal meningitis is a neglected tropical disease that is responsible for a large proportion of AIDS-related deaths across Africa; however, the ecological determinants that underlie a patient's risk of infection remain largely unexplored...
October 19, 2016: Molecular Ecology
https://www.readbyqxmd.com/read/27855158/high-resolution-genetics-identifies-the-lipid-transfer-protein-sec14p-as-target-for-antifungal-ergolines
#17
Ireos Filipuzzi, Simona Cotesta, Francesca Perruccio, Britta Knapp, Yue Fu, Christian Studer, Verena Pries, Ralph Riedl, Stephen B Helliwell, Katarina T Petrovic, N Rao Movva, Dominique Sanglard, Jianshi Tao, Dominic Hoepfner
Invasive infections by fungal pathogens cause more deaths than malaria worldwide. We found the ergoline compound NGx04 in an antifungal screen, with selectivity over mammalian cells. High-resolution chemogenomics identified the lipid transfer protein Sec14p as the target of NGx04 and compound-resistant mutations in Sec14p define compound-target interactions in the substrate binding pocket of the protein. Beyond its essential lipid transfer function in a variety of pathogenic fungi, Sec14p is also involved in secretion of virulence determinants essential for the pathogenicity of fungi such as Cryptococcus neoformans, making Sec14p an attractive antifungal target...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27853789/chemical-and-functional-properties-of-metal-chelators-that-mobilize-copper-to-elicit-fungal-killing-of-cryptococcus-neoformans
#18
Marian E Helsel, Elizabeth J White, Sayyeda Zeenat A Razvi, Bruno Alies, Katherine J Franz
A panel of iron (Fe) and copper (Cu) chelators was screened for growth inhibitory activity against the fungal pathogen Cryptococcus neoformans. Select bidentate metal-binding ligands containing mixed O,S or O,N donor atoms were identified as agents that induce cell killing in a Cu-dependent manner. Conversely, structurally similar ligands with O,O donor atoms did not inhibit C. neoformans growth regardless of Cu status. Studies of Cu(ii) and Cu(i) binding affinity, lipophilicity, and growth recovery assays of Cu-import deficient cells identified lipophilicity of thermodynamically stable Cu(II)L2 complexes as the best predictor of antifungal activity...
November 17, 2016: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/27853088/disseminated-cryptococcosis-in-a-63-year-old-patient-with-multiple-sclerosis-treated-with-fingolimod
#19
Hiroyuki Seto, Mitsushige Nishimura, Katsuhiro Minamiji, Sonoko Miyoshi, Hiroyuki Mori, Kenji Kanazawa, Hisafumi Yasuda
We herein report the case of a 63-year-old man who presented with a 3-month history of a cutaneous nodular lesion of his jaw, low grade fever, lethargy and progressive cognitive impairment. He had a 30-year history of multiple sclerosis and had been treated with fingolimod for the previous 2 years. Laboratory data revealed CD4 lymphocytopenia and a tissue culture of the skin nodule was positive for Cryptococcus neoformans. Cerebrospinal fluid and serum cryptococcal antigen tests were also positive and we diagnosed him to have disseminated cryptococcosis...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27851904/role-of-pathogen-associated-molecular-patterns-pamps-in-immune-responses-to-fungal-infections
#20
Mehdi Taghavi, Alireza Khosravi, Esmaeil Mortaz, Donya Nikaein, Seyyed Shamsadin Athari
Recent years have seen the rise of invasive fungal infections, which are mostly due to the increase in patients. Three major opportunistic fungal species in human are Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans that pose the biggest concern for these immunocompromised patients' mortality. The growing occurrence of opportunistic fungal infections has sparked the interest to understand defense mechanisms against pathogenic fungi. Toll-like receptors (TLRs), as a part of innate immune system, play an important role for recognizing the invading microorganisms and initiating sufficient immune responses...
November 13, 2016: European Journal of Pharmacology
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