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Hormographiella aspergillata: an emerging basidiomycete in the clinical setting? A case report and literature review.
Moniot, M, Lavergne, RA, Morel, T, Guieze, R, Morio, F, Poirier, P, Nourrisson, C
BMC infectious diseases. 2020;(1):945
Abstract
BACKGROUND Filamentous basidiomycetes are mainly considered to be respiratory tract colonizers but the clinical significance of their isolation in a specimen is debatable. Hormographiella aspergillata was first reported as a human pathogen in 1971. We discuss the role of this mold as a pathogen or colonizer and give an update on diagnostic tools and in vitro antifungal susceptibility. CASE PRESENTATION We identified three cases of H. aspergillata with respiratory symptoms in a short period of time. One invasive infection and two colonizations were diagnosed. Culture supernatants showed that H. aspergillata can produce galactomannan and β-D-glucan but not glucuronoxylomannan. For the first time, isavuconazole susceptibility was determined and high minimum inhibitory concentrations (MICs) were found. Liposomal amphotericin B and voriconazole have the lowest MICs. CONCLUSION To date, 22 invasive infections involving H. aspergillata have been reported. On isolation of H. aspergillata, its pathogenic potential in clinical settings can be tricky. Molecular identification and antifungal susceptibility testing are essential considering high resistance against several antifungal therapies.
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Comprehensive review on Caelsalpinioideae lectins: From purification to biological activities.
Cavada, BS, Pinto-Junior, VR, Osterne, VJS, Oliveira, MV, Lossio, CF, Silva, MTL, Bari, AU, Lima, LD, Souza-Filho, CHD, Nascimento, KS
International journal of biological macromolecules. 2020;:333-348
Abstract
Lectins are a class of proteins with specific and reversible carbohydrate binding properties. Plant lectins constitute the group of these proteins most studied, placing emphasis on the legume family. The Caesalpinioideae subfamily is part of Leguminosae and second only to Papilionoideae with more published works on lectins. Classically, Caesalpinioideae is formed by 171 genera and 2250 species. It presents 13 genera with reports of lectins, featuring the Bauhinia genus with the greatest number of species having purified and characterized lectins. Comparing genera, the lectins in this subfamily do not have similar physicochemical or structural properties. Collectively, however, antibacterial, antiviral, and anticancer activities have been reported, as well as applications as biosensors and biomarkers. This review aims to summarize the available data on purified lectins from species of the Caesalpinioideae subfamily, demonstrating the characteristics of these molecules and the potential for their application in future studies of new lectins, as well as of application in several areas.
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Effect of initial antifungal therapy on mortality among patients with bloodstream infections with different Candida species and resistance to antifungal agents: A multicentre observational study by the Turkish Fungal Infections Study Group.
Doğan, Ö, Yeşilkaya, A, Menekşe, Ş, Güler, Ö, Karakoç, Ç, Çınar, G, Kapmaz, M, Aydın, M, Keske, Ş, Şahin, S, et al
International journal of antimicrobial agents. 2020;(1):105992
Abstract
This study aimed to describe the effect of initial antifungal therapy on patient mortality and to detail the current distribution and resistance patterns of Candida spp. among patients with candidaemia. A prospective observational study was performed among consecutive patients with candidaemia from 10 Turkish medical centres between January 2015 and November 2018. The primary outcome was 10-day mortality. Species were identified using MALDI-TOF/MS. A total of 342 patients with candidaemia were included, of which 175 (51.2%) were male and 68 (19.9%) were aged <18 years. The most common species were Candida albicans (47.4%), Candida parapsilosis (26.6%), Candida tropicalis (9.6%) and Candida glabrata (7.6%). Among all Candida spp., the 10-day case fatality rate (CFR) was 32.2%. The CFR was highest in patients with C. albicans (57.3%) and lowest in patients with C. parapsilosis (21.8%). The resistance rate to fluconazole was 13% in C. parapsilosis, with no significant effect on mortality. No resistance to echinocandins was detected. In the multivariate analysis, being in the ICU [OR = 2.1 (95% CI 1.32-3.57); P = 0.002], renal failure [OR = 2.4 (1.41-3.97); P = 0.001], total parenteral nutrition [OR = 2 (1.22-3.47); P = 0.006], C. albicans infection [OR = 1.7 (1.06-2.82); P = 0.027] and echinocandin as primary agent [OR = 0.6 (0.36-0.99); P = 0.047] were significantly associated with mortality. Candidaemia is a deadly infection. Fluconazole resistance is emerging, although it was not significantly related to mortality. Using an echinocandin as the primary agent could be life-saving.
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Invasive Tracheobronchial Aspergillosis in Critically Ill Patients with Severe Influenza. A Clinical Trial.
Nyga, R, Maizel, J, Nseir, S, Chouaki, T, Milic, I, Roger, PA, Van Grunderbeeck, N, Lemyze, M, Totet, A, Castelain, S, et al
American journal of respiratory and critical care medicine. 2020;(5):708-716
Abstract
Rationale: Invasive tracheobronchial aspergillosis (ITBA) is an uncommon but severe clinical form of invasive pulmonary aspergillosis in which the fungal infection is entirely or predominantly confined to the tracheobronchial tree.Objectives: To analyze the diagnostic and prognostic differences between tracheobronchial aspergillosis and pulmonary aspergillosis without tracheobronchial lesions among patients admitted to the ICU with severe influenza.Methods: This retrospective, observational study included critically ill patients with influenza associated with pulmonary aspergillosis from three hospital ICUs between 2010 and 2019. Patient characteristics and clinical and mycologic data at admission and during ICU stay were collected in a database to evaluate variables in the two groups.Measurements and Main Results: Thirty-five patients admitted to the ICU with severe influenza and pulmonary aspergillosis were included. Ten patients were included in the group with ITBA (n = 10 of 35; 28.6%), and 25 patients were included in the group without ITBA. The group with ITBA comprised more patients with active smoking, diabetes mellitus, and higher severity scores (Simplified Acute Physiology Score II). Ninety-day mortality rates in the groups with and without ITBA were 90% and 44%, respectively (P = 0.02). Moreover, significantly higher serum 1,3-β-d-glucan and galactomannan and BAL fluid galactomannan concentrations were observed in the group with ITBA compared with the group without ITBA (P < 0.0001, P = 0.003, and P = 0.008, respectively).Conclusions: ITBA was associated with higher severity scores, mortality, and serum and BAL fluid galactomannan and 1,3-β-d-glucan concentrations than invasive pulmonary aspergillosis without tracheobronchial lesions. ITBA should be systematically researched by bronchoscopic examination in ICU patients with concomitant pulmonary aspergillosis and influenza.Clinical trial registered with www.clinicaltrials.gov (NCT04077697).
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Mechanisms of triazole resistance in Aspergillus fumigatus.
Nywening, AV, Rybak, JM, Rogers, PD, Fortwendel, JR
Environmental microbiology. 2020;(12):4934-4952
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Abstract
The ubiquitous fungal pathogen Aspergillus fumigatus is the primary cause of opportunistic mould infections in humans. Aspergilli disseminate via asexual conidia passively travelling through air currents to germinate within a broad range of environs, wherever suitable nutrients are found. Though the average human inhales hundreds of conidia daily, A. fumigatus invasive infections primarily affect the immunocompromised. At-risk individuals can develop often fatal invasive disease for which therapeutic options are limited. Regrettably, the global insurgence of isolates resistant to the triazoles, the frontline antifungal class used in medicine and agriculture to control A. fumigatus, is complicating the treatment of patients. Triazole antifungal resistance in A. fumigatus has become recognized as a global, yet poorly comprehended, problem. Due to a multitude of factors, the magnitude of resistant infections and their contribution to treatment outcomes are likely underestimated. Current studies suggest that human drug-resistant infections can be either environmentally acquired or de novo host selected during patient therapy. While much concerning development of resistance is yet unknown, recent investigations have revealed assorted underlying mechanisms enabling triazole resistance within individual clinical and environmental isolates. This review will provide an overview of triazole resistance as it is currently understood, as well as highlight some of the prominent biological mechanisms associated with clinical and environmental resistance to triazoles in A. fumigatus.
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Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba.
Walvekar, S, Anwar, A, Anwar, A, Sridewi, N, Khalid, M, Yow, YY, Khan, NA
Acta tropica. 2020;:105618
Abstract
Acanthamoeba spp. are free living amoeba (FLA) which are widely distributed in nature. They are opportunistic parasites and can cause severe infections to the eye, skin and central nervous system. The advances in drug discovery and modifications in the chemotherapeutic agents have shown little improvement in morbidity and mortality rates associated with Acanthamoeba infections. The mechanism-based process of drug discovery depends on the molecular drug targets present in the signaling pathways in the genome. Synthetic libraries provide a platform for broad spectrum of activities due to their desired structural modifications. Azoles, originally a class of synthetic anti-fungal drugs, disrupt the fungal cell membrane by inhibiting the biosynthesis of ergosterol through the inhibition of cytochrome P450 dependent 14α-lanosterol, a key step of the sterol pathway. Acanthamoeba and fungi share the presence of similar sterol intermediate, as ergosterol is also the major end-product in the sterol biosynthesis in Acanthamoeba. Sterols present in the eukaryotic cell membrane are one of the most essential lipids and exhibit important structural and signaling functions. Therefore, in this review we highlight the importance of specific targeting of ergosterol present in Acanthamoebic membrane by azole compounds for amoebicidal activity. Previously, azoles have also been repurposed to report antimicrobial, antiparasitic and antibacterial properties. Moreover, by loading the azoles into nanoparticles through advanced techniques in nanotechnology, such as physical encapsulation, adsorption, or chemical conjugation, the pharmacokinetics and therapeutic index of the drugs can be significantly improved. The current review proposes an important strategy to target Acanthamoeba using synthetic libraries of azoles and their conjugated nanoparticles for the first time.
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Proteomic analysis of the inhibitory effect of the butanolic fraction of Jacquinia macrocarpa on Fusarium verticillioides.
Valenzuela-Cota, DF, Morales-Amparano, MB, Plascencia-Jatomea, M, Martínez-Cruz, O, Hernández-García, F, Vázquez-Moreno, L, Rosas-Burgos, EC, Huerta-Ocampo, JÁ
Canadian journal of microbiology. 2020;(10):535-548
Abstract
Jacquinia macrocarpa, a plant native to northwestern Mexico, has an inhibitory effect against phytopathogenic fungi. Previous studies have shown that the butanolic extract of J. macrocarpa causes retardation and atrophy in mycelial growth of Fusarium verticillioides. However, the action mechanism of this extract is unknown. We used a proteomics approach to understand the inhibitory effect of J. macrocarpa butanolic extract, based on differential protein accumulation in F. verticillioides. Proteins were extracted from F. verticillioides cultured in Czapek broth with and without 202.12 μg/mL (IC50) of butanolic extract of J. macrocarpa. Thirty-eight protein spots showing statistically significant changes (ANOVA, p < 0.01) and at least a 2-fold change in abundance between experimental conditions were analyzed by mass spectrometry. Identified proteins were grouped into different biological processes according to Gene Ontology, among them were amino acid metabolism, protein folding and stabilization, protein degradation, protein transport, carbohydrate metabolism, oxidative stress response, and miscellaneous. This work is the first report of changes in the proteomic profile of F. verticillioides exposed to the J. macrocarpa extract. This information provides new insights into the inhibitory mechanism of the extract and represents a starting point for dissection of the fungal response against the J. macrocarpa extract components.
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High frequency of azole resistant Candida spp. colonization among presumptive multidrug resistant tuberculosis (MDR-TB) patients.
Darma, S, Ambara, A, Aman, AT, Annisa, L, Nurrokhman, , Nuryastuti, T, Wibawa, T
PloS one. 2020;(11):e0242542
Abstract
BACKGROUND Tuberculosis is one of the major causes of death globally. The problems become even more complicated with the rise in prevalence of multidrug resistant tuberculosis (MDR-TB). Many diseases have been reported to occur with tuberculosis making it more difficult to manage. Candida spp., which are yeast-like fungi and a constituent of normal flora in humans, are notoriously reported to be one of the most common opportunistic nosocomial infections. This study aimed to measure the proportion of presumptive MDR-TB patients colonized with Candida spp. and to characterize its susceptibility against azole group antifungal agents. METHODS Sputum from presumptive MDR-TB patients were collected and examined for the presence of Mycobacterium tuberculosis and its rifampicin resistant status using GeneXpert. It was further cultured on Sabouroud's Dextrose Agar (SDA) to isolate the Candida spp. The Candida species were determined using HiCrome™ Candidal Differential Agar. Antifungal susceptibility was tested using microbroth dilution methods. Checkerboard microdilution assays were performed to measure the interaction between rifampicin and fluconazole to C. albicans. RESULTS There were 355 presumptive MDR-TB patients enrolled. A total of 101 (28.4%) patients were confirmed to have M. tuberculosis. There were 113 (31.8%) sputum positive for Candida spp., which corresponded to 149 Candida spp. isolates. Candida albicans was the most frequent (53.7%) species isolated from all patients. The susceptibility of Candida spp. against fluconazole, itraconazole, and ketoconazole were 38.3%, 1.3%, and 10.7% respectively. There was significant association between rifampicin exposure history and susceptibility of Candida albicans against fluconazole (Odds Ratio: 9.96; 95% CI: 1.83-54.19; p <0.01), but not for ketoconazole and itraconazole. The checkerboard microdilution assays showed that rifampicin decreased the fungicidal activity of fluconazole to C. albicans in a dose-dependent manner. CONCLUSION There was high frequency of azole resistant Candida spp. isolates colonizing the respiratory tract of presumptive MDR-TB patients. This presence might indicate the association of chronic exposure to rifampicin, the main drug for tuberculosis therapy, with the induction of azole resistance.
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Medication association and immunomodulation: An approach in fungal diseases and in particular in the treatment of paracoccidioidomycosis.
Santos, LA, Grisolia, JC, Malaquias, LCC, Paula, FBA, Dias, ALT, Burger, E
Acta tropica. 2020;:105412
Abstract
Fungal infections have been increasing in recent decades, mainly affecting immunocompromised individuals, although certain mycoses, such as paracoccidioidomycosis (PCM), infect immunologically competent individuals. The major problems observed regarding fungal diseases are inadequate diagnosis, prolonged treatment time, the reduced number of drugs available for treatment, in addition to the fact that there are no vaccines for clinical use. Drug combination in order to immunomodulate the immune response is a new strategy used for the treatment of mycoses, since it is difficult to develop new antifungal drugs. The aim of this study is to present and analyze strategies recently suggested for the treatment of fungi of medical interest, in particular for PCM, such as the utilization of combinations of protein fractions or dead microorganisms, as vaccinal antigens, and cellular immunotherapy. We will also propose new therapeutic alternatives, such as lipids, vitamins, synthetic or natural products as well as the use of low intensity LASER therapy (LLLT) to modulate the immune response of the host, enhancing the efficiency of the existing treatments of mycoses of medical interest and in particular of PCM.
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Adapting to survive: How Candida overcomes host-imposed constraints during human colonization.
Alves, R, Barata-Antunes, C, Casal, M, Brown, AJP, Van Dijck, P, Paiva, S
PLoS pathogens. 2020;(5):e1008478
Abstract
Successful human colonizers such as Candida pathogens have evolved distinct strategies to survive and proliferate within the human host. These include sophisticated mechanisms to evade immune surveillance and adapt to constantly changing host microenvironments where nutrient limitation, pH fluctuations, oxygen deprivation, changes in temperature, or exposure to oxidative, nitrosative, and cationic stresses may occur. Here, we review the current knowledge and recent findings highlighting the remarkable ability of medically important Candida species to overcome a broad range of host-imposed constraints and how this directly affects their physiology and pathogenicity. We also consider the impact of these adaptation mechanisms on immune recognition, biofilm formation, and antifungal drug resistance, as these pathogens often exploit specific host constraints to establish a successful infection. Recent studies of adaptive responses to physiological niches have improved our understanding of the mechanisms established by fungal pathogens to evade the immune system and colonize the host, which may facilitate the design of innovative diagnostic tests and therapeutic approaches for Candida infections.