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Aspergillus fumigatus

Cristina Nativi, David Goyard, Veronica Baldoneschi, Annabelle Varrot, Michele Fiore, Anne Imberty, Barbara Richichi, Olivier Renaudet
Bacterial and fungal pathogens involved in lung infection in cystic fibrosis patients utilize a particular family of glycan-binding proteins, characterized by the presentation of six fucose-binding sites on a ring shape scaffold. These lectins are attractive targets for anti-infectious compounds that could interfere in the recognition of host tissues by pathogens. The design of a cyclopeptide-based hexavalent structure allowed for the presentation of six fucose residues. The synthetic hexavalent compound displays appropriate geometry resulting in high avidity binding by lectins from Aspergillus fumigatus and Burkholderia ambifaria...
December 14, 2017: Bioconjugate Chemistry
Jason E Gilde, Christopher C Xiao, Victoria A Epstein, Jonathan Liang
INTRODUCTION: Acute invasive fungal rhinosinusitis (AIFRS) is a potentially fatal infection, usually affecting immunocompromised patients. Isolated sphenoid sinus involvement is rare and has been reported in only a few cases. We discuss the clinical characteristics, histopathologic features, and differential diagnosis of AIFRS of the sphenoid sinus. CASE PRESENTATION: A 57-year-old man with a history of refractory non-Hodgkin lymphoma and neutropenia presented with a 1-week duration of left-sided headache and ipsilateral cheek paresthesia...
2017: Permanente Journal
Luis A Ramírez-Camejo, Génesis Maldonado-Morales, Paul Bayman
Drosophila melanogaster has become a model system to study interactions between innate immunity and microbial pathogens, yet many aspects regarding its microbial community and interactions with pathogens remain unclear. In this study wild D. melanogaster were collected from tropical fruits in Puerto Rico to test how the microbiota is distributed and to compare the culturable diversity of fungi and bacteria. Additionally, we investigated whether flies are potential vectors of human and plant pathogens. Eighteen species of fungi and twelve species of bacteria were isolated from wild flies...
2017: International Journal of Microbiology
Ali Mohd Lone, Muneer Ahmad Bhat, Muzafar Ahmad Rather, Wajaht Amin Shah, Zubair Shanib Bhat, Irfan Qadir Tantry, Poonam Prakash
The study was designed with an aim to synthesize a series of 2-(((2-ether)amino)methylene)-dimedone derivatives and evaluate the synthesized compounds for antimicrobial activity. Compound library was synthesized by reaction with alkyl, alkenyl, alkynyl and alicyclic bromo-compounds. Characterization of the synthesized compounds was performed by 1H NMR, 13C NMR and mass spectral techniques. The compounds were evaluated for their antibacterial activity against Gram-positive (Staphylococcus aureus, Bacillus subtilis, Clostridium sporogenes) and Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli)...
December 9, 2017: Microbial Pathogenesis
G Morán, B Uberti, A Ortloff, H Folch
Neutrophils are the predominant inflammatory cells that infiltrate airways during acute exacerbation of asthma. The importance of A. fumigatus sensitization, and IgE response in the airways in patients with acute asthma is unclear. Rockefeller (RK) mice were sensitized with A. fumigatus extract protein. The animals were subsequently challenged with different degrees of A. fumigatus contamination in the cage bedding. All groups of mice were euthanized to obtain bronchoalveolar lavage fluid (BALF) for cytological and Elisa assays, and lung tissue for histological analysis...
December 7, 2017: Journal de Mycologie Médicale
Sourabh Dhingra, Jay C Buckey, Robert A Cramer
Recent estimates suggest that more than 3 million people have chronic or invasive fungal infections, causing more than 600,000 deaths every year. Aspergillus fumigatus causes invasive pulmonary aspergillosis (IPA) in patients with compromised immune systems and is a primary contributor to increases in human fungal infections. Thus, developing new clinical modalities as standalone or adjunctive therapy for improving IPA patient outcomes is critically needed. Here we test the in vitro and in vivo impact of hyperbaric oxygen (100% oxygen, >1 ATA) (HBO) on A...
December 11, 2017: Antimicrobial Agents and Chemotherapy
Michaela Lackner, Günter Rambach, Emina Jukic, Bettina Sartori, Josef Fritz, Christoph Seger, Magdalena Hagleitner, Cornelia Speth, Cornelia Lass-Flörl
No data are available on the in vivo impact of infections with in vitro azole-resistant Aspergillus fumigatus in immunocompetent hosts. Here, the aim was to investigate fungal fitness and treatment response in immunocompetent mice infected with A. fumigatus (parental strain [ps]) and isogenic mutants carrying either the mutation M220K or G54W (cyp51A). The efficacy of itraconazole (ITC) and posaconazole (PSC) was investigated in mice, intravenously challenged either with a single or a combination of ps and mutants (6 × 105 conidia/mouse)...
December 8, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Jessica J Talbot, Paul Thompson, Larry Vogelnest, Vanessa R Barrs
Aspergillosis is a major cause of severe respiratory disease in birds. The prevalence of cryptic section Fumigati and other non-Aspergillus fumigatus species as causative agents is unknown. Species identity was determined in 30 isolates from affected birds from zoos, pet birds and poultry by PCR of the ITS1-5.8S-ITS2 and partial β-tubulin genes. The most prevalent isolate was A. fumigatus sens. str. in 87% (26) cases. Other Aspergillus species were identified in 13% (4) cases, including A. restrictus (1), A...
December 8, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Hilary Renshaw, José M Vargas-Muñiz, Praveen R Juvvadi, Amber D Richards, Greg Waitt, Erik J Soderblom, M Arthur Moseley, William J Steinbach
Myosins are critical motor proteins that contribute to the secretory pathway, polarized growth, and cytokinesis. The globular tail domains of class V myosins have been shown to be important for cargo binding and actin cable organization. Additionally, phosphorylation plays a role in class V myosin cargo choice. Our previous studies on the class V myosin, MyoE, in the fungal pathogen Aspergillus fumigatus confirmed its requirement for normal morphology and virulence. However, the domains and molecular mechanisms governing MyoE's function remain unknown...
December 8, 2017: Journal of Cell Science
Stanislaw Schmidt, Lars Tramsen, Andreas Schneider, Ralf Schubert, Ada Balan, Özer Degistirici, Roland Meisel, Thomas Lehrnbecher
Mesenchymal stromal cells (MSCs) are increasingly given as immunotherapy to hematopoietic stem cell transplant (HSCT) recipients with refractory graft-versus-host disease (GvHD). Whereas the immunosuppressive properties of MSCs seem to be beneficial in GvHD, there is, at the same time, major concern that MSCs increase the risk for infection. We therefore investigated the interplay of human MSCs with Aspergillus fumigatus and the impact of MSCs on different arms of the anti-Aspergillus host response in vitro...
November 10, 2017: Oncotarget
Shiv D Kale, Tariq Ayubi, Dawoon Chung, Nuria Tubau-Juni, Andrew Leber, Ha X Dang, Saikumar Karyala, Raquel Hontecillas, Christopher B Lawrence, Robert A Cramer, Josep Bassaganya-Riera
Incidences of invasive pulmonary aspergillosis, an infection caused predominantly by Aspergillus fumigatus, have increased due to the growing number of immunocompromised individuals. While A. fumigatus is reliant upon deficiencies in the host to facilitate invasive disease, the distinct mechanisms that govern the host-pathogen interaction remain enigmatic, particularly in the context of distinct immune modulating therapies. To gain insights into these mechanisms, RNA-Seq technology was utilized to sequence RNA derived from lungs of 2 clinically relevant, but immunologically distinct murine models of IPA on days 2 and 3 post inoculation when infection is established and active disease present...
December 6, 2017: Scientific Reports
Zhikai Guo, Cuijuan Gai, Caihong Cai, Liangliang Chen, Shoubai Liu, Yanbo Zeng, Jingzhe Yuan, Wenli Mei, Haofu Dai
Fungi residing in mangroves are considered to be a bank of novel bioactive natural products. In the screening for bioactive metabolites from mangrove-derived fungi, the ethyl acetate extract of the fermentation broth of Aspergillus fumigatus JRJ111048, a fungus isolated from the leaves of the mangrove plant Acrostichum specioum endemic to Hainan island, was found to possess insecticidal activity against Spodoptera litura. Bioactivity-guided isolation lead to the discovery of seven metabolites 1-7, including one new anhydride derivative aspergide (1), one new lipid amide 11-methyl-11-hydroxyldodecanoic acid amide (2), and five known compounds; α-ethyl glucoside (3), spiculisporic acid B (4), spiculisporic acid C (5), spiculisporic acid (6), and secospiculisporic acid B (7)...
December 6, 2017: Marine Drugs
Shuwen Deng, Lili Zhang, Yanfeng Ji, Paul E Verweij, Kin Ming Tsui, Ferry Hagen, Jos Houbraken, Jacque F Meis, Parida Abliz, Xiaodong Wang, Jingjun Zhao, Wanqing Liao
This study investigated the triazole phenotype and genotypic of clinical Aspergillus fumigatus isolates from China. We determined the triazole susceptibility profiles of 159 A. fumigatus isolates collected between 2011 and 2015 from four different areas in China tested against 10 antifungal drugs using the Clinical Laboratory Standard Institute M38-A2 method. For the seven itraconazole-resistant A. fumigatus isolates identified in the study, the cyp51A gene, including its promoter region, was sequenced and the mutation patterns were characterized...
December 6, 2017: Emerging Microbes & Infections
Nuo Sun, Dongmei Li, Yuhan Zhang, Kyle Killeen, William Groutas, Richard Calderone
The lack of new antifungal compounds with unique mechanisms of action is a concern for therapeutic management of patients. To identify inhibitors against human pathogenic fungi, we screened ~3000 compounds provided by the Developmental Therapeutics Program of NIH/NCI against a panel of pathogenic fungi including Candida species, Aspergillus fumigatus, and Cryptococcus neoformans. NSC319726 (a thiosemicarbazone) had broad antifungal activity in the range of 0.1-2.0 µg/ml and was also inhibitory to fluconazole-resistant isolates of Candida species...
December 5, 2017: Scientific Reports
Do-Yeon Cho, Kyle J Hoffman, Gobind S Gill, Dong-Jin Lim, Daniel Skinner, Calvin Mackey, Steven M Rowe, Bradford A Woodworth
Objective: Amphotericin B (AMB), a potent antifungal agent, has been employed as topical and systemic therapy for sinonasal fungal infections. A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of fungal infections has been recently developed to provide greater protection from AMB toxicity than current, clinically approved lipid-based formulations. The objective of the current study was to evaluate the safety and potency of ND-AMB for sinonasal delivery using an in vitro model...
March 2017: World journal of otorhinolaryngology—head and neck surgery
Hiroki Takahashi, Yoko Kusuya, Daisuke Hagiwara, Azusa Takahashi-Nakaguchi, Kanae Sakai, Tohru Gonoi
BACKGROUND: Aspergillus fumigatus is a human fungal pathogen that causes aspergillosis in immunocompromised hosts. A. fumigatus is believed to be exposed to diverse environmental stresses in the host cells. The adaptation mechanisms are critical for infections in human bodies. Transcriptional networks in response to diverse environmental challenges remain to be elucidated. To gain insights into the adaptation to environmental stresses in A. fumigatus mycelia, we conducted time series transcriptome analyses...
December 4, 2017: BMC Genomics
Urszula Nawrot, Beata Sulik-Tyszka, Ewelina Kurzyk, Martyna Mroczyńska, Katarzyna Włodarczyk, Marta Wróblewska, Grzegorz Władysław Basak, Anna Brillowska-Dąbrowska
The aim of this study was to evaluate the accuracy of commercial gradient test (Etest) in the detection of triazole resistant Aspergillus fumigatus isolates using reference microdilution methods and the analysis of sequences of the cyp 51A gene. The study was performed on twenty clinical isolates which were identified as Aspergillus fumigatus based on the DNA sequences of the ITS1-2 fragment of ribosomal DNA and the β-tubulin gene, out of them seventeen isolates showed wild -type cyp51A sequence and three were positive for the mutation TR34/L98H...
November 30, 2017: Acta Biochimica Polonica
Qusai Al Abdallah, Wenbo Ge, Jarrod R Fortwendel
CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 is a novel genome-editing system that has been successfully established in Aspergillus fumigatus. However, the current state of the technology relies heavily on DNA-based expression cassettes for delivering Cas9 and the guide RNA (gRNA) to the cell. Therefore, the power of the technology is limited to strains that are engineered to express Cas9 and gRNA. To overcome such limitations, we developed a simple and universal CRISPR-Cas9 system for gene deletion that works across different genetic backgrounds of A...
November 2017: MSphere
Laure Nicolas Annick Ries, Sarah Beattie, Robert A Cramer, Gustavo H Goldman
It is estimated that fungal infections, caused most commonly by Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, result in more deaths annually than malaria or tuberculosis. It has long been hypothesized the fungal metabolism plays a critical role in virulence though specific nutrient sources utilized by human pathogenic fungi in vivo has remained enigmatic. However, the metabolic utilisation of preferred carbon and nitrogen sources, encountered in a host niche-dependent manner, is known as carbon catabolite and nitrogen catabolite repression (CCR, NCR), and has been shown to be important for virulence...
December 2, 2017: Molecular Microbiology
Rachana Chaturvedi, Ashvini Kolhe, Kirti Pardeshi, Leena Naik, Shashir Wanjare
Aspergillus species are ubiquitous opportunistic molds that cause both allergic and invasive syndromes. A 65-year-old female, farmer by occupation, presented with left upper limb and trunk swelling for one year, associated with pain, tightening of skin, and vesicles with watery discharge. Local examination showed a diffuse swelling extending from left arm to forearm and lateral chest wall associated with edema, induration, and raised temperature. The swelling was firm to hard with superficial skin ulcers and black eschar...
November 30, 2017: Diagnostic Cytopathology
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