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Aspergillus fumigatus

Maiken Cavling Arendrup, Paul E Verweij, Johan W Mouton, Katrien Lagrou, Joseph Meletiadis
Objectives: Azole-resistant Aspergillus fumigatus is emerging worldwide. Reference susceptibility testing methods are technically demanding and no validated commercial susceptibility tests for moulds currently exist. In this multicentre study a 4-well azole-containing screening agar method was evaluated using clinically relevant isolates. Methods: Forty WT and 39 cyp51A mutant A. fumigatus [G54 (n = 10), M220 (n = 10), TR34/L98H (n = 9) and TR46/Y121F/T289A (n = 10)] were tested individually and as simulated mixed samples (sampling 4 WT and 1 mutant colonies)...
October 4, 2017: Journal of Antimicrobial Chemotherapy
Junjie Han, Congcong Liu, Li Li, Hui Zhou, Li Liu, Li Bao, Qian Chen, Fuhang Song, Lixin Zhang, Erwei Li, Ling Liu, Yunfei Pei, Cheng Jin, Yanfen Xue, Wenbing Yin, Yanhe Ma, Hongwei Liu
New tetramic acid derivatives, (±)-conipyridoins A-D (1-4), conipyridoins E (5) and F (6), as well as new 4-hydroxy-2-pyridone alkaloids (±)-didymellamide E (7), (+)-didymellamide B (8), (+)-N-hydroxyapiosporamide (9), and didymellamides F-H (10-12) were isolated and identified from the solid culture of the fungus Coniochaeta cephalothecoides. Chiral resolution of 1, 2, 3, 4, and 7 gave five pairs of enantiomers, 1a/1b, 2a/2b, 3a/3b, 4a/4b, and 7a/7b, respectively. Stereochemistry of 1a and 1b, 2a and 2b, was established and confirmed by the single-crystal X-ray diffraction and electronic circular dichroism (ECD) methods...
October 11, 2017: Journal of Organic Chemistry
Laura Bedin Denardi, Jéssica Tairine Keller, Maria Isabel de Azevedo, Vanessa Oliveira, Fernanda Baldissera Piasentin, Cecília Bittencourt Severo, Janio Morais Santurio, Sydney Hartz Alves
The checkerboard broth microdilution assay (BMD) is the most frequently used method for the in vitro evaluation of drug combinations. However, its use to evaluate the effect of antifungal drugs on filamentous fungi is sometimes associated with endpoint-reading difficulties, and different degrees of interaction are assigned to the same drug combination. We evaluated combinations of the azoles, itraconazole, posaconazole, and voriconazole, with the echinocandins, anidulafungin, caspofungin, and micafungin, against 15 itraconazole-resistant Aspergillus fumigatus clinical strains via the checkerboard BMD and Etest assay...
October 9, 2017: Mycopathologia
Anthony Nash, Johanna Rhodes
Azole antifungal drugs target CYP51A in Aspergillus fumigatus by binding with the active site of the protein, blocking ergosterol biosynthesis. Resistance to azole antifungal drugs is now common, with a leucine to histidine amino acid substitution at position 98 the most frequent, predominantly conferring resistance to itraconazole, although cross-resistance has been reported in conjunction with other mutations. In this study, we create a homology model of CYP51A using a recently published crystal structure of the paralog protein CYP51B...
September 9, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Patrick C Y Woo, Susanna K P Lau, Candy C Y Lau, Edward T K Tung, Rex K H Au-Yeung, Jian-Pao Cai, Ken T K Chong, Kong Hung Sze, Richard Y Kao, Quan Hao, Kwok-Yung Yuen
Recently, we showed that Mp1p is an important virulence factor of Talaromyces marneffei, a dimorphic fungus phylogenetically closely related to Aspergillus fumigatus. In this study, we investigated the virulence properties of the four Mp1p homologues (Afmp1p, Afmp2p, Afmp3p, and Afmp4p) in A. fumigatus using a mouse model. All mice died 7 days after challenge with wild-type A. fumigatus QC5096, AFMP1 knockdown mutant, AFMP2 knockdown mutant and AFMP3 knockdown mutant and 28 days after challenge with AFMP4 knockdown mutant (P<...
August 4, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Emrah Şişli, Yasemin Özdemir Şahan, Mehmet Fatih Ayık, Deniz Nart, Yüksel Atay
A 3-year-old girl with the diagnosis of chronic granulomatous disease (CGD) was hospitalized for bronchopneumonia and congestive heart failure. Her medical history included methylprednisolone medication for autoimmune gastric outlet obstruction. Computed tomography revealed pneumonic infiltrations and pericardial thickening. A pulsed-wave Doppler recording revealed E/A >1. During a pericardiectomy, multiple islands of thick, firm-walled, fibrinous exudate-containing, small abscess formations were observed...
October 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
Nagehan Emiralioğlu, Hatice Nursun Özcan, Diclehan Orhan, Mithat Haliloğlu, Ali Bülent Cengiz, Elmas Ebru Yalçın, Deniz Doğru Ersöz, Nural Kiper, Hayriye Uğur Özçelik
Chronic necrotizing pulmonary aspergillosis (CNPA) is a condition caused by the ubiquitous fungus Aspergillus fumigatus in non-immunocompromised individuals. Numerous underlying conditions have been associated with CNPA. Tuberculosis, non-tuberculous mycobacterial infection and allergic bronchopulmonary aspergillosis (ABPA) remain the predominant risk factors for development of CNPA. Development of CNPA in echinococcal cyst cavities is very rare and the optimal therapeutic regimen and treatment duration have not been established...
June 2017: Tüberküloz Ve Toraks
Vanessa Espinosa, Orchi Dutta, Constance McElrath, Peicheng Du, Yun-Juan Chang, Bryan Cicciarelli, Amy Pitler, Ian Whitehead, Joshua J Obar, Joan E Durbin, Sergei V Kotenko, Amariliz Rivera
Type III interferons (IFN-λs) are the most recently found members of the IFN cytokine family and engage IFNLR1 and IL10R2 receptor subunits to activate innate responses against viruses. We have identified IFN-λs as critical instructors of antifungal neutrophil responses. Using Aspergillus fumigatus (Af) as a model to study antifungal immune responses, we found that depletion of CCR2(+) monocytes compromised the ability of neutrophils to control invasive fungal growth. Using an unbiased approach, we identified type I and III IFNs as critical regulators of the interplay between monocytes and neutrophils responding to Af We found that CCR2(+) monocytes are an important early source of type I IFNs that prime optimal expression of IFN-λ...
October 6, 2017: Science Immunology
Hasan Nazik, Lydia-Marie Joubert, Patrick R Secor, Johanna M Sweere, Paul L Bollyky, Gabriele Sass, Lynette Cegelski, David A Stevens
Pseudomonas aeruginosa (Pa) and Candida albicans (Ca) are major bacterial and fungal pathogens in immunocompromised hosts, and notably in the airways of cystic fibrosis patients. The bacteriophages of Pa physically alter biofilms, and were recently shown to inhibit the biofilms of Aspergillus fumigatus. To understand the range of this viral-fungal interaction, we studied Pa phages Pf4 and Pf1, and their interactions with Ca biofilm formation and preformed Ca biofilm. Both forms of Ca biofilm development, as well as planktonic Ca growth, were inhibited by either phage...
October 6, 2017: Microbiology
Simone Santana Aguiar, Neiva Damaceno, Wilma Carvalho Neves Forte
OBJECTIVE: To evaluate the results of the tests used to identify the IgE mediated sensitization to Aspergillus fumigatus in patients with cystic fibrosis. METHODS: This is a cross-sectional descriptive study with a convenience sample of 86 patients diagnosed with cystic fibrosis in the Reference Service in Cystic Fibrosis at a tertiary teaching hospital. The following tests were performed to assess the sensitization to A. fumigatus in patients with cystic fibrosis: Total serum IgE, eosinophil count, fungus detection through oropharyngeal swab or sputum culture, serum-specific IgE, and immediate-type hypersensitivity (IgE) skin tests...
July 2017: Revista Paulista de Pediatria: Orgão Oficial da Sociedade de Pediatria de São Paulo
Sara Mina, Cindy Staerck, Agnès Marot, Charlotte Godon, Alphonse Calenda, Jean-Philippe Bouchara, Maxime J J Fleury
Scedosporium species rank the second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF), after Aspergillus fumigatus. In CF, these fungi may cause various respiratory infections similar to those caused by A. fumigatus, including bronchitis and allergic broncho-pulmonary mycoses. Diagnosis of these infections relies on the detection of serum antibodies using crude antigenic extracts. However, many components of these extracts are common to Scedosporium and Aspergillus species, leading to cross-reactions...
August 26, 2017: Diagnostic Microbiology and Infectious Disease
Emmanuel Stephen-Victor, Anupama Karnam, Thierry Fontaine, Anne Beauvais, Mrinmoy Das, Pushpa Hegde, Praveen Prakhar, Sahana Holla, Kithiganahalli N Balaji, Srini V Kaveri, Jean-Paul Latgé, Vishukumar Aimanianda, Jagadeesh Bayry
Background: Human dendritic cell (DC) response to α-(1,3)-glucan polysaccharide of Aspergillus fumigatus and ensuing CD4 + T cell polarization are poorly characterized. Methods: α-(1,3)-Glucan was isolated from A. fumigatus conidia and mycelia cell wall. For the analysis of polarization, DCs and autologous naïve CD4 + T cells were co-cultured. Phenotype of immune cells was analysed by flow cytometry and cytokines by ELISA. Blocking antibodies were used to dissect the role of TLR2 and PD-L1 in regulating α-(1,3)-glucan-mediated DC activation and T cell responses...
September 8, 2017: Journal of Infectious Diseases
A F A D Schauwvlieghe, A G Vonk, E P Buddingh, R A S Hoek, V A Dalm, C H W Klaassen, B J A Rijnders
Background: The AsperGenius ® assay is a multiplex real-time PCR test that allows the simultaneous detection of Aspergillus species and identification of the most common mutations in the Aspergillus fumigatus cyp51A gene conferring resistance (TR 34 /L98H and TR 46 /T289A/Y121F) by using melting curve analysis. Mixed infections with azole-resistant and susceptible A. fumigatus have rarely been described. Methods: The AsperGenius ® multiplex real-time PCR assay (PathoNostics, Maastricht, the Netherlands) was used on bronchoalveolar lavage (BAL) samples of 91 consecutive patients with a suspected invasive Aspergillus infection at the Erasmus MC University Medical Center, Rotterdam...
August 9, 2017: Journal of Antimicrobial Chemotherapy
Gurpreet Singh, Archana Katoch, Mod Razak, Anindya Goswami, Meenu Katoch
The present study describes 32 fungal endophytes isolated from different tissues of Brugmansia aurea Lagerh. Each fungal strain was authenticated based on ITS rDNA sequence. Phylogenetic analysis showed that these fungi are distributed in 3 classes, 7 orders and 12 genera. The dichloromethane extracts of endophytic strains were screened for anticancer and antimicrobial activity. Anticancer activity of extracts against human cancer cell lines revealed that fifty % strains are active with IC50 < 10 μg/mL...
September 12, 2017: FEMS Microbiology Letters
M Falahati, S Ghanbari, M Ebrahimi, M Ghazanfari, F Bazrafshan, S Farahyar, R Falak
BACKGROUND AND PURPOSE: Allergy is an undesired immune response to non-pathogenic agents. However, some opportunistic microorganisms such as fungi can also cause allergy. Among those fungi, hyphae form of Aspergillus strains including A. fumigatus, A. flavus, and A. niger could be mentioned. In this study, we aimed to separate allergic proteins from Aspergillus strains and determine their identity. MATERIALS AND METHODS: Standard species of Aspergillus strains were cultivated in optimized conditions and the mycelium was separated by centrifugation...
December 2016: Advances in Medical Mycology (Iran)
Nitya Meenakshi Raman, Suganthi Ramasamy
Accurate characterization of melanin using analytical methodologies has proved to be difficult due to its heterogeneity, insolubility in wide pH and broad range of solvents. The present study was undertaken to characterize melanin extracted from an environmental Aspergillus fumigatus AFGRD105 by studying its genes, chemical properties and spectral data. A gene based approach to confirm the type of melanin carried out indicated the extracted melanin to be of the dihydroxynaphthalene type. On comparison with synthetic melanin, UV-Vis and IR spectra of the extracted melanin revealed characteristic peaks that can be further used for confirmation of DHN-melanin extracted from any source...
December 2017: Biochemistry and Biophysics Reports
Pegah Seddigh, Thilo Bracht, Valerie Molinier-Frenkel, Flavia Castellano, Olaf Kniemeyer, Marc Schuster, Juliane Weski, Anja Hasenberg, Andreas Kraus, Gernot Poschet, Thomas Hager, Dirk Theegarte, Christiane Opitz, Axel A Brakhage, Barbara Sitek, Mike Hasenberg, Matthias Gunzer
The ubiquitous mold Aspergillus fumigatus threatens immunosuppressed patients as inducer of lethal invasive aspergillosis. A. fumigatus conidia are airborne and reach the alveoli, where they encounter alveolar epithelial cells (AEC). Previous studies reported the importance of the surfactant-producing AEC II during A. fumigatus infection via in vitro experiments using cell lines. We established a negative isolation protocol yielding untouched primary murine AEC II with a purity >90 %, allowing ex vivo analyses of the cells, which encountered the mold in vivo...
September 26, 2017: Molecular & Cellular Proteomics: MCP
Jui-Hsuan Yang, Un-In Wu, Huei-Min Tai, Wang-Huei Sheng
BACKGROUND: Healthcare-associated infections caused by multidrug-resistant (MDR) pathogens are significantly associated with increased mortality and morbidity. Environmental cleaning can reduce transmission of these pathogens but is often inadequate. Adjunctive methods are warranted to enhance the effectiveness of disinfection particularly in hospital settings where healthcare-associated infections are of major concern. METHODS: We conducted a study to examine the effectiveness of a mobile, automatic device, Hyper Light Disinfection Robot (model: Hyper Light P3), which utilized ultraviolet-C (UV-C) to kill MDR-Pseudomonas aeruginosa, MDR- Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), Mycobacterium abscessus and Aspergillus fumigatus...
September 18, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Alayna K Caffrey-Carr, Caitlin H Kowalski, Sarah R Beattie, Nathan A Blaseg, Chanell R Upshaw, Arsa Thammahong, Hannah E Lust, Yi-Wei Tang, Tobias M Hohl, Robert A Cramer, Joshua J Obar
Heterogeneity amongst Aspergillus fumigatus isolates results in unique virulence potential and inflammatory responses. How these isolates drive specific immune responses and how this affects fungal-induced lung damage and disease outcome is unresolved. We demonstrate that the highly virulent CEA10 strain is able to rapidly germinate within the immune competent lung environment inducing greater lung damage, vascular leakage, and IL-1α release compared to the low virulent Af293 strain that germinates with lower frequency in this environment...
September 25, 2017: Infection and Immunity
Valdirene S Muniz, Juliana C Silva, Yasmim A V Braga, Rossana C N Melo, Shigeharu Ueki, Masahide Takeda, Akira Hebisawa, Koichiro Asano, Rodrigo T Figueiredo, Josiane S Neves
BACKGROUND: Eosinophils mediate the immune response in different infection conditions. The release of extracellular DNA traps (ETs) by leukocytes has been described as an innate immune response mechanism that is relevant in many disorders including fungal diseases. Different stimuli induce human eosinophil ETs (EETs) release. Aspergillus fumigatus (A. fumigatus) is an opportunistic fungus that may cause eosinophilic allergic bronchopulmonary aspergillosis (ABPA). It has been reported that eosinophils are important to the clearance of A...
September 21, 2017: Journal of Allergy and Clinical Immunology
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