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Cryptococcus neoformans

Giuseppe Ianiri, Kylie J Boyce, Alexander Idnurm
Discovering the genes underlying fundamental processes that enable cells to live and reproduce is a technical challenge, because loss of gene function in mutants results in organisms that cannot survive. This study describes a forward genetics method to identify essential genes in fungi, based on the propensity for Agrobacterium tumefaciens to insert T-DNA molecules into the promoters or 5' untranslated regions of genes and by placing a conditional promoter within the T-DNA. Insertions of the promoter of the GAL7 gene were made in the human pathogen Cryptococcus neoformans...
October 25, 2016: Current Genetics
Yee-Seul So, Dong-Hoon Yang, Kwang-Woo Jung, Won-Ki Huh, Yong-Sun Bahn
In this study, we aimed to generate a series of versatile tagging plasmids that can be used in diverse molecular biological studies of the fungal pathogen Cryptococcus neoformans. We constructed 12 plasmids that can be used to tag a protein of interest with a GFP, mCherry, 4×FLAG, or 6×HA along with nourseothricin, neomycin, or hygromycin-resistant selection markers. Using this tagging plasmid set, we explored the adenylyl cyclase complex (ACC), consisting of adenylyl cyclase (Cac1) and its associated protein Aca1, in the cAMP-signaling pathway, which is critical for the pathogenicity of C...
October 25, 2016: Journal of Microbiology and Biotechnology
Shahriyar Taghavi-Moghadam, Cecil D Kwong, John A Secrist, Shabana I Khan, Alice M Clark
Eupolauridine, an indenonaphthyridine alkaloid, has been previously reported by us to exhibit antifungal activity. This study describes the synthesis of new alkyl and benzyl naphthyridinium/pyridinium analogs of eupolauridine as potential antifungal agents. A majority of the analogs exhibited antifungal activity against opportunistic pathogens such as Candida albicans and Cryptococcus neoformans. Several of them were also effective against bacteria (Staphylococcus aureus, MRS, Pseudomonas and Mycobacterium) and the malaria parasite (Plasmodium falciparum) to variable extents...
February 23, 2016: Bioorganic & Medicinal Chemistry
Mojgan Aminnejad, Massimo Cogliati, Shuyao Duan, Michael Arabatzis, Kathrin Tintelnot, Elizabeth Castañeda, Marcia Lazéra, Aristea Velegraki, David Ellis, Tania C Sorrell, Wieland Meyer
Cryptococcus neoformans and C. gattii are pathogenic basidiomycetous yeasts and the commonest cause of fungal infection of the central nervous system. Cryptococci are typically haploid but several inter-species, inter-varietal and intra-varietal hybrids have been reported. It has a bipolar mating system with sexual reproduction occurring normally between two individuals with opposite mating types, α and a. This study set out to characterize hybrid isolates within the C. neoformans/C. gattii species complex: seven unisexual mating intra-varietal VNI/VNII (αAAα) and six novel inter-varietal VNII/VNIV (aADα)...
2016: PloS One
Nicole Robbins, Gerard D Wright, Leah E Cowen
Invasive fungal infections are becoming an increasingly important cause of human mortality and morbidity, particularly for immunocompromised populations. The fungal pathogens Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus collectively contribute to over 1 million human deaths annually. Hence, the importance of safe and effective antifungal therapeutics for the practice of modern medicine has never been greater. Given that fungi are eukaryotes like their human host, the number of unique molecular targets that can be exploited for drug development remains limited...
October 2016: Microbiology Spectrum
Aritreyee Datta, Vikas Yadav, Anirban Ghosh, Jaesun Choi, Dipita Bhattacharyya, Rajiv K Kar, Humaira Ilyas, Arkajyoti Dutta, Eunseol An, Jayanta Mukhopadhyay, Dongkuk Lee, Kaustuv Sanyal, Ayyalusamy Ramamoorthy, Anirban Bhunia
There is a significant need for developing compounds that kill Cryptococcus neoformans, the fungal pathogen that causes meningoencephalitis in immunocompromised individuals. Here, we report the mode of action of a designed antifungal peptide, VG16KRKP (VARGWKRKCPLFGKGG) against C. neoformans. It is shown that VG16KRKP kills fungal cells mainly through membrane compromise leading to efflux of ions and cell metabolites. Intracellular localization, inhibition of in vitro transcription, and DNA binding suggest a secondary mode of action for the peptide, hinting at possible intracellular targets...
October 18, 2016: Biophysical Journal
Ross D Blundell, Simon J Williams, Samantha D M Arras, Jessica L Chitty, Kirsten L Blake, Daniel J Ericsson, Nidhi Tibrewal, Jurgen Rohr, Y Q Andre E Koh, Ulrike Kappler, Avril A B Robertson, Mark S Butler, Matthew A Cooper, Bostjan Kobe, James A Fraser
Opportunistic fungal pathogens such as Cryptococcus neoformans are a growing cause of morbidity and mortality among immunocompromised populations worldwide. To address the current paucity of antifungal therapeutic agents, further research into fungal-specific drug targets is required. Adenylosuccinate synthetase (AdSS) is a crucial enzyme in the adeosine triphosphate (ATP) biosynthetic pathway, catalyzing the formation of adenylosuccinate from inosine monophosphate and aspartate. We have investigated the potential of this enzyme as an antifungal drug target, finding that loss of function results in adenine auxotrophy in C...
September 9, 2016: ACS Infectious Diseases
Debora L Oliveira, Fernanda L Fonseca, Daniel Zamith-Miranda, Leonardo Nimrichter, Jéssica Rodrigues, Marcos D Pereira, Julia Cv Reuwsaat, Augusto Schrank, Charley Staats, Livia Kmetzsch, Marilene H Vainstein, Marcio L Rodrigues
AIM: We investigated the involvement of the autophagy protein 7 (Atg7) in physiology and pathogenic potential of Cryptococcus neoformans. MATERIALS & METHODS: The C. neoformans gene encoding Atg7 was deleted by biolistic transformation for characterization of autophagy mechanisms, pigment formation, cell dimensions, interaction with phagocytes and pathogenic potential in vivo. RESULTS & CONCLUSION: ATG7 deletion resulted in defective autophagy mechanisms, enhanced pigmentation and increased cellular size both in vitro and in vivo...
October 18, 2016: Future Microbiology
Nicole Robbins, Michaela Spitzer, Wenliang Wang, Nicholas Waglechner, Dhruv J Patel, Jonathan S O'Brien, Linda Ejim, Obi Ejim, Mike Tyers, Gerard D Wright
Natural products are invaluable historic sources of drugs for infectious diseases; however, the discovery of novel antimicrobial chemical scaffolds has waned in recent years. Concurrently, there is a pressing need for improved therapeutics to treat fungal infections. We employed a co-culture screen to identify ibomycin, a large polyketide macrolactone that has preferential killing activity against Cryptococcus neoformans. Using chemical and genome methods, we determined the structure of ibomycin and identified the biosynthetic cluster responsible for its synthesis...
October 7, 2016: Cell Chemical Biology
S Marques, R Carmo, I Ferreira, M Bustorff, S Sampaio, M Pestana
BACKGROUND: In solid organ transplant patients, 8% of invasive fungal infections are attributed to Cryptococcus. The aim of this study was to determine the frequency, risk factors, clinical characteristics, and outcome of kidney transplant recipients (TR) infected with Cryptococcus. CASE SERIES: Between 2007 and 2014, a total of 500 kidney transplantations were performed at São João Hospital, in Porto, Portugal. Six infections by C. neoformans were reported, an incidence of 1...
September 2016: Transplantation Proceedings
Fernanda Sangalli-Leite, Liliana Scorzoni, Ana Carolina Alves de Paula E Silva, Julhiany de Fátima da Silva, Haroldo Cesar de Oliveira, Junya de Lacorte Singulani, Fernanda Patrícia Gullo, Rosangela Moraes da Silva, Luis Octávio Regasini, Dulce Helena Siqueira da Silva, Vanderlan da Silva Bolzani, Ana Marisa Fusco-Almeida, Maria José Soares Mendes-Giannini
Cryptococcosis is an opportunistic fungal infection responsible for high morbidity and mortality in immunocompromised patients. Combination of antifungal substances is a promising way to increase the percentage of successful treatment. Pedalitin (PED) is a natural substance obtained from Pterogyne nitens. The aim of this study was to verify the efficacy of PED alone and in combination with amphotericin B (AmB) in vitro and in vivo against Cryptococcus spp. In the in vitro assay, minimum inhibitory concentrations (MICs) of 0...
September 29, 2016: International Journal of Antimicrobial Agents
Shankar Thangamani, Hassan E Eldesouky, Haroon Mohammad, Pete E Pascuzzi, Larisa Avramova, Tony R Hazbun, Mohamed N Seleem
BACKGROUND: Ebselen, an organoselenium compound and a clinically safe molecule has been reported to possess potent antifungal activity, but its antifungal mechanism of action and in vivo antifungal activity remain unclear. METHODS: The antifungal effect of ebselen was tested against Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, Cryptococcus neoformans, and C. gattii clinical isolates. Chemogenomic profiling and biochemical assays were employed to identify the antifungal target of ebselen...
October 3, 2016: Biochimica et Biophysica Acta
Samantha D M Arras, Sheena M H Chua, Maha S I Wizrah, Joshua A Faint, Amy S Yap, James A Fraser
Low rates of homologous integration have hindered molecular genetic studies in Cryptococcus neoformans over the past 20 years, and new tools that facilitate genome manipulation in this important pathogen are greatly needed. To this end, we have investigated the use of a Class 2 CRISPR system in C. neoformans (formerly C. neoformans var. grubii). We first expressed a derivative of the Streptococcus pyogenes Cas9 nuclease in C. neoformans, and showed that it has no effect on growth, production of virulence factors in vitro, or virulence in a murine inhalation model...
2016: PloS One
Norida Vélez, Patricia Escandón
The propagules of the fungal species Cryptococcus neoformans and C. gattii, whose varieties are distributed world wide, are the primary cause of cryptococcosis, a life threatening disease. The study of environmental and clinical isolates of Cryptococcosis is an important contribution to the epidemiology and ecology of the fungus. The aim of this work was to determine the presence of C. neoformans and C. gattii in the environment in Bogotá, Colombia's capital city and to establish the relation between clinical and environmental isolates in the period 2012-2015...
October 3, 2016: Memórias do Instituto Oswaldo Cruz
John F Fisher, Paula A Valencia-Rey, William B Davis
Background.  There are no prospective data regarding the management of pulmonary cryptococcosis in the immunocompetent patient. Clinical guidelines recommend oral fluconazole for patients with mild to moderate symptoms and amphotericin B plus flucytosine followed by fluconazole for severe disease. It is unclear whether patients who have histological evidence of Cryptococcus neoformans but negative cultures will even respond to drug treatment. We evaluated and managed a patient whose presentation and course raised important questions regarding the significance of negative cultures, antifungal choices, duration of therapy, and resolution of clinical, serologic, and radiographic findings...
September 2016: Open Forum Infectious Diseases
Kevin Felipe Cruz Martho, Amanda Teixeira de Melo, Juliana Possato Fernandes Takahashi, Juliana Mariotti Guerra, Dayane Cristina da Silva Santos, Sônia Ueda Purisco, Márcia de Souza Carvalho Melhem, Raquel Dos Anjos Fazioli, Clerlune Phanord, Patrícia Sartorelli, Marcelo A Vallim, Renata C Pascon
Fungal opportunistic pathogens colonize various environments, from plants and wood to human and animal tissue. Regarding human pathogens, one great challenge during contrasting niche occupation is the adaptation to different conditions, such as temperature, osmolarity, salinity, pressure, oxidative stress and nutritional availability, which may constitute sources of stress that need to be tolerated and overcome. As an opportunistic pathogen, C. neoformans faces exactly these situations during the transition from the environment to the human host, encountering nutritional constraints...
2016: PloS One
Cristiane Bigatti Pereira, Nívea Pereira de Sá, Beatriz Martins Borelli, Carlos Augusto Rosa, Paulo Jorge Sanches Barbeira, Betania Barros Cota, Susana Johann
The antifungal effects of two eicosanoic acids, 2-amino-3,4-dihydroxy-2-25-(hydroxymethyl)-14-oxo-6,12-eicosenoic acid (compound 1) and myriocin (compound 2), isolated from Mycosphaerella sp. were evaluated against Cryptococcus neoformans and C. gattii. The compounds displayed antifungal activities against several isolates of C. neoformans and C. gattii, with minimal inhibitory concentration (MIC) values ranging from 0.49 to 7.82 μM for compound 1 and 0.48-1.95 μM for compound 2. In the checkerboard microtiter test, both compounds exhibited synergistic activity with amphotericin B against C...
September 28, 2016: Microbial Pathogenesis
Mattehew E Mead, Christina M Hull
No abstract text is available yet for this article.
October 2016: Journal of Microbiology / the Microbiological Society of Korea
Thais Pandini Figueiredo, Rosymar Coutinho de Lucas, Rodrigo Anselmo Cazzaniga, Carolina Nunes França, Fernando Segato, Rafael Taglialegna, Claudia Maria Leite Maffei
Cryptococcosis is a leading invasive fungal infection in immunocompromised patients. Considering the high prevalence and severity of these infections in immunocompromised patients attended at HC-FMRP-USP, the present research aimed to characterize the clinical isolates of Cryptococcus strains by biochemical and molecular methods and evaluate antifungal susceptibility of clinical isolates. Fifty isolates from 32 HIV-positive patients were obtained at HC-FMRP-USP. Most of the isolates (78.1%) were identified as C...
2016: Revista do Instituto de Medicina Tropical de São Paulo
Kyung-Tae Lee, Yee-Seul So, Dong-Hoon Yang, Kwang-Woo Jung, Jaeyoung Choi, Dong-Gi Lee, Hyojeong Kwon, Juyeong Jang, Li Li Wang, Soohyun Cha, Gena Lee Meyers, Eunji Jeong, Jae-Hyung Jin, Yeonseon Lee, Joohyeon Hong, Soohyun Bang, Je-Hyun Ji, Goun Park, Hyo-Jeong Byun, Sung Woo Park, Young-Min Park, Gloria Adedoyin, Taeyup Kim, Anna F Averette, Jong-Soon Choi, Joseph Heitman, Eunji Cheong, Yong-Hwan Lee, Yong-Sun Bahn
Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades...
2016: Nature Communications
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