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https://www.readbyqxmd.com/read/29466605/continuous-sheath-free-separation-of-drug-treated-human-fungal-pathogen-cryptococcus-neoformans-by-morphology-in-biocompatible-polymer-solutions
#1
Di Li, Jessica Zielinski, Lukasz Kozubowski, Xiangchun Xuan
Cryptococcal meningitis caused by Cryptococcus neoformans is the leading cause of fungal central nervous system infections. Current antifungal treatments for cryptococcal infections are inadequate partly due to the occurrence of drug resistance. Recent studies indicate that the treatment of the azole drug fluconazole changes the morphology of C. neoformans to form enlarged "multimeras" that consist of three or more connected cells/buds. To analyze if these multimeric cells are a prerequisite for C...
February 21, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29463005/mechanisms-of-pulmonary-escape-and-dissemination-by-cryptococcus-neoformans
#2
REVIEW
Steven T Denham, Jessica C S Brown
Cryptococcus neoformans is a common environmental saprophyte and human fungal pathogen that primarily causes disease in immunocompromised individuals. Similar to many environmentally acquired human fungal pathogens, C. neoformans initiates infection in the lungs. However, the main driver of mortality is invasive cryptococcosis leading to fungal meningitis. After C. neoformans gains a foothold in the lungs, a critical early step in invasion is transversal of the respiratory epithelium. In this review, we summarize current knowledge relating to pulmonary escape...
February 17, 2018: Journal of Fungi (Basel, Switzerland)
https://www.readbyqxmd.com/read/29456239/a-rare-presentation-of-cryptococcal-meningitis-and-cerebellitis-in-an-asplenic-patient-seronegative-for-human-immunodeficiency-virus-hiv
#3
Hafsa Abbas, Angelica CiFuentes Kottkamp, Naeem Abbas, Richard Cindrich, Manisha Singh
BACKGROUND Cryptococcal meningitis in patients who are seronegative for the human immunodeficiency virus (HIV) and in patients who are splenectomized is rare. This report is an unusual case of meningeal and cerebellar infection due to the encapsulated yeast, Cryptococcus neoformans, which has not previously been associated with asplenia. CASE REPORT A 65-year-old HIV-negative patient with a previous splenectomy, presented with a three-day history of fever, vomiting, and headache. His symptoms progressed to generalized body aches, persistent fever, and neck stiffness...
February 19, 2018: American Journal of Case Reports
https://www.readbyqxmd.com/read/29420767/evaluation-of-trypan-blue-stain-in-the-tc20-automated-cell-counter-as-a-point-of-care-for-the-enumeration-of-viable-cryptococcal-cells-in-cerebrospinal-fluid
#4
Richard Kwizera, Andrew Akampurira, Tadeo K Kandole, Maria S Nabaggala, Darlisha A Williams, Andrew Kambugu, David B Meya, Joshua Rhein, David R Boulware
Cerebrospinal fluid (CSF) culture can determine a quantitative viability of Cryptococcus yeasts; however, culture has a long turnaround-time. The TC20 automated cell counter (Bio-Rad) is a benchtop instrument used to count cells in 30 seconds. In vitro studies suggest trypan blue staining can distinguish between viable and dead cryptococcal yeasts. We hypothesized that trypan blue staining with automated cell counting may provide rapid quantification of viable CSF Cryptococcus yeasts. In sum, 96 HIV-infected participants with cryptococcal meningitis were enrolled and provided 194 CSF specimens in Kampala, Uganda...
October 9, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29382737/udp-glucuronic-acid-transport-is-required-for-virulence-of-cryptococcus-neoformans
#5
Lucy X Li, Carsten Rautengarten, Joshua L Heazlewood, Tamara L Doering
Glycans play diverse biological roles, ranging from structural and regulatory functions to mediating cellular interactions. For pathogens, they are also often required for virulence and survival in the host. In Cryptococcus neoformans, an opportunistic pathogen of humans, the acidic monosaccharide glucuronic acid (GlcA) is a critical component of multiple essential glycoconjugates. One of these glycoconjugates is the polysaccharide capsule, a major virulence factor that enables this yeast to modulate the host immune response and resist antimicrobial defenses...
January 30, 2018: MBio
https://www.readbyqxmd.com/read/29377368/a-systematic-review-of-fluconazole-resistance-in-clinical-isolates-of-cryptococcus-species
#6
REVIEW
Felix Bongomin, Rita O Oladele, Sara Gago, Caroline B Moore, Malcolm D Richardson
Fluconazole is the most commonly used antifungal agent for both the treatment of cryptococcal meningitis, and for prophylaxis against the disease. However, its prolonged use has the potential to exert selection pressure in favour of fluconazole-resistant strains. We evaluated the prevalence of fluconazole resistance of Cryptococcus spp. clinical isolates in 29 studies from 1988 to May 2017 included in EMBASE and MEDLINE databases. A total of 4,995 Cryptococcus isolates from 3,210 patients constituted this study; 248 (5...
January 29, 2018: Mycoses
https://www.readbyqxmd.com/read/29374632/cryptococcal-meningitis-in-a-daily-cannabis-smoker-without-evidence-of-immunodeficiency
#7
Bryan B Shapiro, Rebecca Hedrick, Brigitte C Vanle, Courtney A Becker, Chris Nguyen, David M Underhill, Margie A Morgan, Joel D Kopple, Itai Danovitch, Waguih William IsHak
Cryptococcal meningitis is a life-threatening condition most commonly observed in immunocompromised individuals. We describe a daily cannabis smoker without evidence of immunodeficiency presenting with confirmed Cryptococcus neoformans meningitis. An investigation of cannabis samples from the patient's preferred dispensary demonstrated contamination with several varieties of Cryptococcus, including C. neoformans, and other opportunistic fungi. These findings raise concern regarding the safety of dispensary-grade cannabis, even in immunocompetent users...
January 26, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29373741/high-rates-of-cerebral-toxoplasmosis-in-hiv-patients-presenting-with-meningitis-in-accra-ghana
#8
Japheth A Opintan, Benedict K Awadzi, Isaac J K Biney, Vincent Ganu, Richard Doe, Ernest Kenu, Rita F Adu, Mary M Osei, Amos Akumwena, Michael E Grigg, Gary A Fahle, Mercy J Newman, Peter R Williamson, Margaret Lartey
Background: Data on adult meningitis among patients infected with the human immunodeficiency virus (HIV) is scarce in western sub-Saharan Africa, including Ghana. Methods: HIV-infected adults with a provisional diagnosis of meningitis were consecutively enrolled, between August 2014 and January 2016. After patient data collection, cerebrospinal fluid (CSF) was obtained and evaluated for microbiological aetiologies, cell counts and biochemistry. Caregiver clinicians provided limited data for inpatients at the end-point of discharge or death...
January 24, 2018: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29371497/neuro-immune-mechanisms-of-anti-cryptococcal-protection
#9
REVIEW
Rebecca A Drummond
Cryptococcal meningitis (CM) is a life-threatening fungal disease affecting both immunosuppressed and immunocompetent people. The main causative agent of CM is Cryptococcus neoformans, a basidiomycete fungus prevalent in the environment. Our understanding of the immune mechanisms controlling C. neoformans growth within the central nervous system (CNS) is poor. However, there have been several recent advances in the field of neuroimmunology regarding how cells resident within the CNS, such as microglia and neurons, can participate in immune surveillance and control of infection...
December 25, 2017: Journal of Fungi (Basel, Switzerland)
https://www.readbyqxmd.com/read/29357302/role-of-the-inositol-pyrophosphate-multikinase-kcs1-in-cryptococcus-inositol-metabolism
#10
Guojian Liao, Yina Wang, Tong-Bao Liu, Gurkirat Kohli, Weidong Qian, Erika Shor, Selvakumar Subbian, Chaoyang Xue
Cryptococcus neoformans is the most common cause of deadly fungal meningitis. This fungus has a complex inositol acquisition and utilization system, and our previous studies have shown the importance of inositol utilization in cryptococcal development and virulence. However, how inositol utilization is regulated in this fungus remains unknown. In this study, we found that inositol, irrespective of the presence of glucose in the media, represses the expression of C. neoformans genes involved in inositol pyrophosphate biosynthesis, including the gene encoding inositol hexakisphosphate kinase Kcs1...
January 18, 2018: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/29346417/xylose-donor-transport-is-critical-for-fungal-virulence
#11
Lucy X Li, Carsten Rautengarten, Joshua L Heazlewood, Tamara L Doering
Cryptococcus neoformans, an AIDS-defining opportunistic pathogen, is the leading cause of fungal meningitis worldwide and is responsible for hundreds of thousands of deaths annually. Cryptococcal glycans are required for fungal survival in the host and for pathogenesis. Most glycans are made in the secretory pathway, although the activated precursors for their synthesis, nucleotide sugars, are made primarily in the cytosol. Nucleotide sugar transporters are membrane proteins that solve this topological problem, by exchanging nucleotide sugars for the corresponding nucleoside phosphates...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29327953/multicentric-cryptococcosis-in-a-congo-african-grey-parrot-psittacus-erithacus-erithacus
#12
Raina S K Schunk, Nicholas E Sitinas, Katherine E Quesenberry, Jessica L Grodio
An approximately 10-year-old, female Congo African grey parrot ( Psittacus erithacus erithacus) developed progressive, unilateral exophthalmos and buphthalmos. Survey radiographs revealed a large, coelomic, soft tissue mass, which was confirmed on computed tomography scan. Aspirates of both the contents of the buphthalmic globe and coelomic mass were consistent with Cryptococcus species. Initial results were later confirmed with serum antigen latex agglutination and polymerase chain reaction testing, and the organism was then identified as Cryptococcus neoformans with DNA sequencing...
December 2017: Journal of Avian Medicine and Surgery
https://www.readbyqxmd.com/read/29317510/the-f-box-protein-fbp1-shapes-the-immunogenic-potential-of-cryptococcus-neoformans
#13
Jorge Masso-Silva, Vanessa Espinosa, Tong-Bao Liu, Yina Wang, Chaoyang Xue, Amariliz Rivera
Cryptococcus neoformans is the main etiologic agent of cryptococcal meningitis and causes a significant number of deadly infections per year. Although it is well appreciated that host immune responses are crucial for defense against cryptococcosis, our understanding of factors that control the development of effective immunity to this fungus remains incomplete. In previous studies, we identified the F-box protein Fbp1 as a novel determinant of C. neoformans virulence. In this study, we found that the hypovirulence of the fbp1Δ mutant is linked to the development of a robust host immune response...
January 9, 2018: MBio
https://www.readbyqxmd.com/read/29311092/pharmacodynamics-of-flubendazole-for-cryptococcal-meningoencephalitis-repurposing-and-reformulation-of-an-anti-parasitic-agent-for-a-neglected-fungal-disease
#14
Gemma L Nixon, Laura McEntee, Adam Johnson, Nikki Farrington, Sarah Whalley, Joanne Livermore, Cristien Natal, Gina Washbourn, Jaclyn Bibby, Neil Berry, Jodi Lestner, Megan Truong, Andrew Owen, David Lalloo, Ian Charles, William Hope
Current therapeutic options for cryptococcal meningitis are limited by toxicity, global supply and emergence of resistance. There is an urgent need to develop additional antifungal agents that are fungicidal within the central nervous system and preferably orally bioavailable. The benzimidazoles have broad-spectrum anti-parasitic activity, but also have in vitro antifungal activity that includes Cryptococcus neoformans Flubendazole (a benzimidazole) has been reformulated by Janssen Pharmaceutica as an amorphous solid drug nanodispersion to develop an orally bioavailable medicine for the treatment of neglected tropical diseases such as onchocerciasis...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29302151/cryptococcal-meningitis-masquerading-as-normal-pressure-hydrocephalus-in-an-immune-competent-adult
#15
Hitesh Raheja, Ankur Sinha, Pavan Kumar Irukulla, Yizhak Kupfer
We report a case of acute cryptococcal meningitis (CM) masquerading as normal pressure hydrocephalus (NPH) in an immune-competent female. An 85-year-old human immunodeficiency virus-negative female presented to the emergency room for altered mental status and difficulty walking. She was increasingly lethargic, with urinary incontinence and gait instability. A previous computed tomography was reported to have ventricular dilatation out of proportion to the degree of cortical atrophy. Magnetic resonance scan of the brain revealed ventricular dilatation and subtle debris layering the occipital horns of the lateral ventricles...
October 2017: Journal of Global Infectious Diseases
https://www.readbyqxmd.com/read/29285049/innate-immune-evasion-strategies-against-cryptococcal-meningitis-caused-by-cryptococcus-neoformans
#16
Cheng-Liang Yang, Jun Wang, Li-Li Zou
As an infectious fungus that affects the respiratory tract, Cryptococcus neoformans (C. neoformans) commonly causes asymptomatic pulmonary infection. C. neoformans may target the brain instead of the lungs and cross the blood-brain barrier (BBB) in the early phase of infection; however, this is dependent on successful evasion of the host innate immune system. During the initial stage of fungal infection, a complex network of innate immune factors are activated. C. neoformans utilizes a number of strategies to overcome the anti-fungal mechanisms of the host innate immune system and cross the BBB...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29284182/cryptococcosis-and-cryptococcal-meningitis-new-predictors-and-clinical-outcomes-at-a-united-states-academic-medical-centre
#17
Bahar H Kashef Hamadani, Carlos Franco-Paredes, Bruce McCollister, Leland Shapiro, J David Beckham, Andrés F Henao-Martínez
As the diagnosis of cryptococcosis is challenging in low-prevalence settings, uncovering predictive factors can improve early diagnosis and timely treatment. The aim of the study was to relate clinical outcomes to predictive variables for the presence of cryptococcosis. A retrospective case-control study matched by collection date, age and gender at a 1:2 ratio (55 cases and 112 controls) was performed in case patients diagnosed with Cryptococcus infection at the University of Colorado Hospital between 2000 and 2017 (n = 167)...
December 28, 2017: Mycoses
https://www.readbyqxmd.com/read/29234588/emerging-fluconazole-resistance-implications-for-the-management-of-cryptococcal-meningitis
#18
Edward Mpoza, Joshua Rhein, Mahsa Abassi
We present the case of an HIV-seropositive individual with cryptococcal meningitis who was found to have a fluconazole resistant strain of Cryptococcus neoformans. The individual required multiple rounds of amphotericin and fluconazole 800-1200 mg after several episodes of clinical relapse. Cerebrospinal fluid sterilization was achieved and maintained with high doses of fluconazole. This case demonstrates the emerging dilemma of increasing rates of fluconazole resistance in Cryptococcus and the clinical difficulties in meningitis management...
March 2018: Medical Mycology Case Reports
https://www.readbyqxmd.com/read/29197141/the-human-blood-brain-barrier-internalizes-cryptococcus-neoformans-via-the-epha2-tyrosine-kinase-receptor
#19
Phylicia A Aaron, Mantana Jamklang, John P Uhrig, Angie Gelli
Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening meningitis most commonly in populations with impaired immunity. Here we resolved the transcriptome of the human brain endothelium challenged with C. neoformans to establish whether C. neoformans invades the CNS by co-opting particular signaling pathways as a means to promote its own entry. Among the 5 major pathways targeted by C. neoformans, the EPH-EphrinA1 (EphA2) tyrosine kinase receptor-signaling pathway was examined further...
December 2, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29187715/-a-silkworm-infection-model-to-evaluate-antifungal-drugs-for-cryptococcosis
#20
Yasuhiko Matsumoto, Masaki Ishii, Kiminori Shimizu, Susumu Kawamoto, Kazuhisa Sekimizu
The development of effective drugs against fungal diseases involves performing infection experiments in animals to evaluate candidate therapeutic compounds. Cryptococcus neoformans is a pathogenic fungus that causes deep mycosis, resulting in respiratory illness and meningitis. Here we describe a silkworm system established to evaluate the safety and efficacy of therapeutic drugs against infection by Cryptococcus neoformans and the advantages of this system over other animal models. The silkworm assay system has two major advantages: 1) silkworms are less expensive to rear and their use is less problematic than that of mammals in terms of animal welfare, and 2) in vivo screenings for identifying candidate drugs can be easily performed using a large number of silkworms...
2017: Medical Mycology Journal
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