Ying Jie Ma, Jie Zhang, Lihong Song, Dennis V Pedersen, Anna Li, John D Lambris, Gregers Rom Andersen, Tom Eirik Mollnes, Peter Garred
Properdin stabilizes the alternative C3 convertase (C3bBb), whereas its role as pattern recognition molecule mediating complement activation is disputed for decades. Previously, we have found that soluble collectin-12 (sCL-12) synergizes complement alternative pathway (AP) activation. However, whether this observation is C3 dependent is unknown. By application of the C3-inhibitor Cp40, we found that properdin in normal human serum bound to Aspergillus fumigatus solely in a C3b dependent manner. Cp40 also prevented properdin binding when properdin-depleted serum reconstituted with purified properdin was applied, in analogy with the findings achieved by C3- depleted serum...
September 10, 2020: ELife
Ling-Shan Yu, Jesus Rodriguez-Manzano, Nicolas Moser, Ahmad Moniri, Kenny Malpartida-Cardenas, Nicholas Miscourides, Thomas Sewell, Tatiana Kochina, Amelie Brackin, Johanna Rhodes, Alison H Holmes, Matthew C Fisher, Pantelis Georgiou
Aspergillus fumigatus has widely evolved resistance to the most commonly used class of antifungal chemicals, the azoles. Current methods for identifying azole resistance are time-consuming and depend on specialized laboratories. There is an urgent need for rapid detection of these emerging pathogens at point-of-care to provide the appropriate treatment in the clinic and to improve management of environmental reservoirs to mitigate the spread of antifungal resistance. Our study demonstrates the rapid and portable detection of the two most relevant genetic markers linked to azole resistance, the mutations TR34 and TR46, found in the promoter region of the gene encoding the azole target, cyp 51A...
September 9, 2020: Journal of Clinical Microbiology
Marco Blickensdorf, Sandra Timme, Marc Thilo Figge
The healthy state of an organism is constantly threatened by external cues. Due to the daily inhalation of hundreds of particles and pathogens, the immune system needs to constantly accomplish the task of pathogen clearance in order to maintain this healthy state. However, infection dynamics are highly influenced by the peculiar anatomy of the human lung. Lung alveoli that are packed in alveolar sacs are interconnected by so called Pores of Kohn. Mainly due to the lack of in vivo methods, the role of Pores of Kohn in the mammalian lung is still under debate and partly contradicting hypotheses remain to be investigated...
2020: Frontiers in Microbiology
Malene Risum, Rasmus Krøger Hare, Jan Berg Gertsen, Lise Kristensen, Helle Krogh Johansen, Jannik Helweg-Larsen, Nissrine Abou-Chakra, Tacjana Pressler, Marianne Skov, Søren Jensen-Fangel, Maiken Cavling Arendrup
Azole-resistant (azole-R) Aspergillus is an increasing challenge worldwide. Patients with cystic fibrosis (CF) are at risk of Aspergillus colonization and disease due to a favorable lung environment for microorganisms. We performed a nationwide study in 2018 of azole-non-susceptible Aspergillus in CF patients and compared with data from two prior studies. All airway samples with mold isolates from patients monitored at the two CF centers in Denmark (RH, Jan-Sept and AUH, Jan-Jun) were included. Classical species identification (morphology and thermo-tolerance) was performed and MALDI-TOF/β-tubulin sequencing was performed if needed...
2020: Frontiers in Microbiology
Joshua J Obar
The mammalian immune system can tune its inflammatory response to the threat level posed by an invading pathogen. It is well established that the host utilizes numerous 'patterns of pathogenicity', such as microbial growth, invasion, and viability, to achieve this tuning during bacterial infections. This review discusses how this notion fits during fungal infection, particularly regarding Aspergillus fumigatus infection. Moreover, how the environmental niches filled by A. fumigatus may drive the evolution of the fungal traits responsible for inducing the strain-specific inflammatory responses that have been experimentally observed will be discussed...
September 5, 2020: Current Opinion in Microbiology
J Dotis, A Kondou, E Koukloumperi, V Karava, A Papadopoulou, C Gkogka, N Printza
Fungal peritonitis in patients undergoing peritoneal dialysis (PD) is very difficult to treat and is associated with significant morbidity and mortality. Among fungal pathogens, Aspergillus peritonitis presents a higher mortality rate when compared to Candida peritonitis and its identification as well as appropriate treatment remains a challenge for the physicians. We critical reviewed all published cases in literature of Aspergillus peritonitis in PD patients. The results showed that a total of 55 cases (51% males) of Aspergillus peritonitis in PD patients were reported from 1968 to 2019...
August 20, 2020: Journal de Mycologie Médicale
Puneet Saxena, Hansraj Choudhary, Valliappan Muthu, Inderpaul Singh Sehgal, Sahajal Dhooria, Kuruswamy Thurai Prasad, Mandeep Garg, Biman Saikia, Ashutosh Nath Aggarwal, Arunaloke Chakrabarti, Ritesh Agarwal
BACKGROUND: The ideal criteria for diagnosing allergic bronchopulmonary aspergillosis (ABPA) remains unknown because of the lack of a gold standard. Latent class analysis (LCA) using a probabilistic modeling technique can circumvent the need for a reference standard. OBJECTIVE: To compare the diagnostic performance of various criteria used for evaluating ABPA. METHODS: We prospectively enrolled consecutive cases of bronchial asthma and performed a series of investigations used for the diagnosis of ABPA...
September 2, 2020: Journal of Allergy and Clinical Immunology in Practice
Bruno Perlatti, Guy Harris, Connie B Nichols, Dulamini I Ekanayake, J Andrew Alspaugh, James B Gloer, Gerald F Bills
Campafungin A is a polyketide that was recognized in the Candida albicans fitness test due to its antiproliferative and antihyphal activity. Its mode of action was hypothesized to involve inhibition of a cAMP-dependent PKA pathway. The originally proposed structure appeared to require a polyketide assembled in a somewhat unusual fashion. However, structural characterization data were never formally published. This background stimulated a reinvestigation in which campafungin A and three closely related minor constituents were purified from fermentations of a strain of the ascomycete fungus Plenodomus enteroleucus ...
September 3, 2020: Journal of Natural Products
Loganathan Gayathri, Mohammad A Akbarsha, Kandasamy Ruckmani
Gliotoxin (GT) and fumagillin (FUM) are mycotoxins most abundantly produced by Aspergillus fumigatus during the early stages of infection to cause invasive aspergillosis (IA). Therefore, we hypothesized that GT and FUM could be the possible source of virulence factors, which we put to test adopting in vitro monoculture and the novel integrated multiple organ co-culture (IdMOC) of A549 and L132 cell. We found that (i) GT is more cytotoxic to lung epithelial cells than FUM, and (ii) GT and FUM act synergistically to inflict pathology to the lung epithelial cell...
September 2, 2020: Scientific Reports
Claudia Lattanzi, Giulia Messina, Valentina Fainardi, Maria Candida Tripodi, Giovanna Pisi, Susanna Esposito
Cystic fibrosis (CF), the most common autosomal-recessive genetic disease in the Caucasian population, is characterized by frequent respiratory infections and progressive lung disease. Fungal species are commonly found in patients with CF, and among them, Aspergillus fumigatus is the most frequently isolated. While bacteria, particularly Pseudomonas aeruginosa , have a well-established negative effect on CF lung disease, the impact of fungal infections remains unclear. In patients with CF, inhalation of Aspergillus conidia can cause allergic bronchopulmonary aspergillosis (ABPA), a Th2-mediated lung disease that can contribute to disease progression...
August 31, 2020: Pathogens
João Ribeiro Memória, Erlan Pércio Lopes Rufino, Pedro Lukas do Rêgo Aquino, Francisco Vaz Guimarães Filho, Túlio Maranhão Neto, Herika Karla Negri Brito de Vasconcelos
Background: Aspergillosis is caused by fungi from the Aspergillus species, mainly Aspergillus fumigatus . Patients with aspergillosis typically have an underlying immunosuppression, and it is rare within the central nervous system (CNS) in an immunocompetent host. The mortality rate is as high as 90% if untreated, and the diagnosis is usually delayed due to nonspecific clinical presentation. This study described a case of CNS aspergillosis in an immunocompetent patient, through which we sought to discuss the current knowledge regarding brain Aspergillus focusing in the immunocompetent host...
2020: Surgical Neurology International
Daisuke Hira, Takuya Onoue, Takuji Oka
Fungal cell walls and their biosynthetic enzymes are potential targets for novel antifungal agents. Recently, two mannosyltransferases, namely core-mannan synthases A (CmsA/Ktr4) and B (CmsB/Ktr7), were found to play roles in the core-mannan biosynthesis of fungal-type galactomannan. CmsA/Ktr4 is an α-(1→2)-mannosyltransferase responsible for α-(1→2)-mannan biosynthesis in fungal-type galactomannan, which covers the cell surface of Aspergillus fumigatus Strains with disrupted cmsA / ktr4 have been shown to exhibit strongly suppressed hyphal elongation and conidiation alongside reduced virulence in a mouse model of invasive aspergillosis, indicating that CmsA/Ktr4 is a potential novel antifungal candidate...
September 1, 2020: Journal of Biological Chemistry
Sebastian Scharf, Anna Bartels, Mustafa Kondakci, Klaus Pfeffer, Birgit Henrich, Rainer Haas
In immunocompromised patients a colonisation with fungi carries the risk to develop serious invasive fungal infection. An early detection is therefore important, but not optimal hitherto. Fortunately, molecular genetic methods have increased the sensitivity of fungal detection and limited the time, until results are available. However, their success depends on an efficient extraction of genomic DNA from the fungal cell in the given diagnostic specimen. To improve the routine DNA preparation method for yeasts and moulds, the impact of bead beating on fungal DNA release was evaluated...
September 2020: International Journal of Medical Microbiology: IJMM
Damaris Lorenzo-Gutiérrez, Lucía Gómez-Gil, Josep Guarro, M Isabel G Roncero, Javier Capilla, Loida López-Fernández
Cu is an essential trace element for cell growth and proliferation. However, excess of Cu accumulation leads to cellular toxicity. Thus, precise and tight regulation of Cu homeostasis processes, including transport, delivery, storage, detoxification, and efflux machineries, is required. Moreover, the maintenance of Cu homeostasis is critical for the survival and virulence of fungal pathogens. Cu homeostasis has been extensively studied in mammals, bacteria, and yeast, but it has not yet been well documented in filamentous fungi...
December 2020: Virulence
Lilyann Novak-Frazer, Samuel P Anees-Hill, Darin Hassan, Rikesh Masania, Caroline B Moore, Malcolm D Richardson, David W Denning, Riina Rautemaa-Richardson
BACKGROUND: Infections caused by triazole drug-resistant Aspergillus fumigatus are an increasing problem. The sensitivity of standard culture is poor, abrogating susceptibility testing. Early detection of resistance can improve patient outcomes, yet tools for this purpose are limited. OBJECTIVES: To develop and validate a pyrosequencing technique to detect resistance-conferring cyp51A polymorphisms from clinical respiratory specimens and A. fumigatus isolates. METHODS: Method validation was performed by Sanger sequencing and pyrosequencing of 50 A...
August 30, 2020: Journal of Antimicrobial Chemotherapy
Kathrin Rothe, Sebastian Rasch, Nina Wantia, Alexander Poszler, Joerg Ulrich, Christoph Schlag, Wolfgang Huber, Roland M Schmid, Dirk H Busch, Tobias Lahmer
Aspergillus spp. cholangitis is an uncommon presentation of invasive aspergillosis. Only few cases are described in the literature affecting severely immunocompromised patients or patients following biliary surgery. Especially, invasive aspergillosis in non-haematological patients is associated with high mortality rates, caused by atypical presentations, which is associated with a delay in diagnosis and therapy. We report a 72-year-old man with primary diagnosis of cholangiocarcinoma and stent implantation by endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression who developed severe cholangitis with invasive aspergillosis...
August 29, 2020: Infection
Isabel Valsecchi, Emmanuel Stephen-Victor, Sarah Sze Wah Wong, Anupama Karnam, Margaret Sunde, J Iñaki Guijarro, Borja Rodríguez de Francisco, Thomas Krüger, Olaf Kniemeyer, Gordon D Brown, Janet A Willment, Jean-Paul Latgé, Axel A Brakhage, Jagadeesh Bayry, Vishukumar Aimanianda
Immune inertness of Aspergillus fumigatus conidia is attributed to its surface rodlet-layer made up of RodAp, characterized by eight conserved cysteine residues forming four disulfide bonds. Earlier, we showed that the conserved cysteine residue point (ccrp ) mutations result in conidia devoid of the rodlet layer. Here, we extended our study comparing the surface organization and immunoreactivity of conidia carrying ccrp-mutations with the RODA deletion mutant (∆ rodA ). Western blot analysis using anti-RodAp antibodies indicated the absence of RodAp in the cytoplasm of ccrp - mutant conidia...
August 26, 2020: Journal of Fungi (Basel, Switzerland)
Amelie P Brackin, Jennifer M G Shelton, Alireza Abdolrasouli, Matthew C Fisher, Thomas R Sewell
The global emergence of azole resistance in Aspergillus fumigatus is resulting in health and food security concerns. Rapid diagnostics and environmental surveillance methods are key to understanding the distribution and prevalence of azole resistance. However, such methods are often associated with high costs and are not always applicable to laboratories based in the least-developed countries. Here, we present and validate a low-cost screening protocol that can be used to differentiate between azole-susceptible "wild-type" and azole-resistant A...
September 2020: Current Protocols in Microbiology
David Connell, Anand Shah
No abstract text is available yet for this article.
August 2020: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Xiaoqiu Cui, Huiyun Wang, Hao Yang, Xiao Li, Xiuzhen Li
Although many entomogenous fungi have been discovered over the years, few studies on the crude extracts of fungi isolated from Cryptotympana atrata with antibacterial and antifungal activity were reported. In this study, total twenty entomogenous fungi were isolated for the first time. And among of them, two pure cultures were identified as Purpureocillium lilacinum and Aspergillus fumigatus with apparent morphology, microscopic identification and 18S rRNA gene sequence. The active strains were fermented to optimize in six different culture media at three different pH values...
August 27, 2020: Antonie Van Leeuwenhoek
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