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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
Samantha Y L Ang, Victor W L Ng, Shree Dinesh Kumar, Sharon Y Y Low
Cryptococcosis is a fungal infection caused by Cryptococcus spp. that enters the body via inhalation. This ubiquitous yeast has gained notoriety as an opportunistic pathogen in the immunosuppressed population. The authors report a case of a previously-well adult male presented with left-sided weakness. Imaging demonstrated a pulmonary mass and 2 contrast-enhancing intracranial lesions-all features suggestive of a primary lung carcinoma with brain metastases. However, further investigations confirmed disseminated cryptococcosis, without evidence of malignancy...
October 18, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
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
Souleymane Sawadogo, Boniface Makumbi, Anne Purfield, Christophine Ndjavera, Gram Mutandi, Andrew Maher, Francina Kaindjee-Tjituka, Jonathan E Kaplan, Benjamin J Park, David W Lowrance
BACKGROUND: Cryptococcal meningitis is common and associated with high mortality among HIV infected persons. The World Health Organization recommends that routine Cryptococcal antigen (CrAg) screening in ART-naïve adults with a CD4+ count <100 cells/μL followed by pre-emptive antifungal therapy for CrAg-positive patients be considered where CrAg prevalence is ≥3%. The prevalence of CrAg among HIV adults in Namibia is unknown. We estimated CrAg prevalence among HIV-infected adults receiving care in Namibia for the purpose of informing routine screening strategies...
2016: PloS One
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
Makoto Nakao, Hideki Muramatsu, Tetsushi Takahashi, Shunsuke Niwa, Yusuke Kagawa, Ryota Kurokawa, Kazuki Sone, Yuki Uozumi, Misako Ohkusu, Katsuhiko Kamei, Hiroshi Koga
A 39-year-old man presented to our hospital with a four-week history of headache and a two-week history of low-grade fever. Chest X-rays showed a tumor of approximately 50 mm in size in the right lower field. A histopathological examination of a transbronchial lung biopsy specimen from the right S9/10 revealed numerous fungal elements that appeared as encapsulated yeast with clear halos. Gadolinium-enhanced brain magnetic resonance images showed multiple cerebral nodules. Cryptococcus gattii (Genotype VGIIa) was isolated from the bronchial lavage and cerebrospinal fluid specimens...
2016: Internal Medicine
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
L F A Guimarães, M Halpern, A S de Lemos, E F de Gouvêa, R T Gonçalves, M A A da Rosa Santos, M Nucci, G Santoro-Lopes
INTRODUCTION: Invasive fungal disease (IFD) is an important complication after solid organ transplantation (SOT). A marked geographic variation in the epidemiology of IFD after kidney transplantation (KT) has been suggested by the results of previous studies. Nevertheless, data from Latin American centers are scarce. OBJECTIVE: This study sought to describe the epidemiology of IFD at a Brazilian KT center. METHODS: This study was a retrospective single-center cohort study that included patients who underwent KT between 1998 and 2009 and were followed up until July 2015...
September 2016: Transplantation Proceedings
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
Gaurav V Sanghvi, Praveen Baskaran, Waltraud Röseler, Bogdan Sieriebriennikov, Christian Rödelsperger, Ralf J Sommer
Nematodes, the earth's most abundant metazoa are found in all ecosystems. In order to survive in diverse environments, they have evolved distinct feeding strategies and they can use different food sources. While some nematodes are specialists, including parasites of plants and animals, others such as Pristionchus pacificus are omnivorous feeders, which can live on a diet of bacteria, protozoans, fungi or yeast. In the wild, P. pacificus is often found in a necromenic association with beetles and is known to be able to feed on a variety of microbes as well as on nematode prey...
2016: PloS One
Karla Silva Teixeira Souza, Cintia Lacerda Ramos, Rosane Freitas Schwan, Disney Ribeiro Dias
The main carbon source used for growth by four yeast strains (Yarrowia lipolytica CCMA 0357, Y. lipolytica CCMA 0242, Wickerhamomyces anomalus CCMA 0358, and Cryptococcus humicola CCMA 0346) and their lipid production were evaluated, using different concentrations of crude and pure glycerol and glucose. Whereas crude glycerol (100 g/L) was the main carbon source used by Y. lipolytica CCMA 0357 (nearly 15 g/L consumed at 120 h) and W. anomalus CCMA 0358 (nearly 45.10 g/L consumed at 48 h), pure glycerol (150 g/L) was the main one used by C...
October 13, 2016: Preparative Biochemistry & Biotechnology
Matthew T Jamison, Jocelyn Macho, Tadeusz F Molinski
Structure-activity relationships of the antifungal aminobisabolene natural product, 1 isolated from Halichondria sp., and synthetic analogs were explored, in parallel with the antidermatophytic allylamine, Terbinafine®, against a panel of pathogenic fungi: Candida spp., Cryptococcus spp. and Trichophyton rubrum. Interpretation of the results suggest different modes of action in antifungal activity for the two classes of compounds.
September 22, 2016: Bioorganic & Medicinal Chemistry Letters
Yasushi Matsuda, Hideki Mitomo, Tetsu Sado, Masafumi Noda, Miki Akiba, Yoshinori Okada
Lung transplantation is getting to be a common treatment for the end-stage respiratory failure. Therefore we might encounter the various issues associated with infection under immunosuppression. At 1st, virus infections occur by Cytomegalovirus, Epstein-Barr virus, hepatitis B and C virus and John Cunningham virus. The 2nd, bacterial infections exacerbate graft condition by methicillin-resistant Staphylococcus aureus, Pseudomonas, Burkholderia cepacia and coagulase negative staphylococci. The 3rd, fungal infections are induced by Aspergillus, Candida and Cryptococcus...
October 2016: Kyobu Geka. the Japanese Journal of Thoracic Surgery
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
Jia Liu, Ming Yuan, Jia-Nan Liu, Li-Jun Lu, Kai-Ming Peng, Xiang-Feng Huang
Four mixed volatile fatty acids (VFAs) were used as sole carbon source to culture oleaginous yeast Cryptococcus curvatus by sequencing batch culture strategy. The highest lipid content (42.7%) and concentration (1.77g/L) were achieved when the ratio of VFAs (acetic, propionic, and butyric acids) was 6:3:1. The oleaginous yeast favored to use VFAs for lipid biosynthesis rather than cell proliferation. With regard to the utilization ratio of VFAs, acetic acid reached over 99%, whereas propionic acid was barely 35%...
October 3, 2016: Bioresource Technology
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