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Journal of Enzyme Inhibition and... Dec 2022With increasing number of immunocompromised patients as well as drug resistance in fungi, the risk of fatal fungal infections in humans increases as well. The action of... (Review)
Review
With increasing number of immunocompromised patients as well as drug resistance in fungi, the risk of fatal fungal infections in humans increases as well. The action of echinocandins is based on the inhibition of β-(1,3)-d-glucan synthesis that builds the fungal cell wall. Caspofungin, micafungin, anidulafungin and rezafungin are semi-synthetic cyclic lipopeptides. Their specific chemical structure possess a potential to obtain novel derivatives with better pharmacological properties resulting in more effective treatment, especially in infections caused by and species. In this review we summarise information about echinocandins with closer look on their chemical structure, mechanism of action, drug resistance and usage in clinical practice. We also introduce actual trends in modification of this antifungals as well as new methods of their administration, and additional use in viral and bacterial infections.
Topics: Antifungal Agents; Aspergillus; Candida; Cell Wall; Drug Design; Echinocandins; Glucans; Microbial Sensitivity Tests; Molecular Structure
PubMed: 35296203
DOI: 10.1080/14756366.2022.2050224 -
Seminars in Respiratory and Critical... Feb 2024The filamentous fungus causes a wide spectrum of diseases in the human lung, with being the most pathogenic and allergenic subspecies. The broad range of clinical... (Review)
Review
The filamentous fungus causes a wide spectrum of diseases in the human lung, with being the most pathogenic and allergenic subspecies. The broad range of clinical syndromes that can develop from the presence of in the respiratory tract is determined by the interaction between host and pathogen. In this review, an oversight of the different clinical entities of pulmonary aspergillosis is given, categorized by their main pathophysiological mechanisms. The underlying immune processes are discussed, and the main clinical, radiological, biochemical, microbiological, and histopathological findings are summarized.
Topics: Humans; Lung; Aspergillus; Pulmonary Aspergillosis; Aspergillus fumigatus
PubMed: 38286136
DOI: 10.1055/s-0043-1777259 -
Clinical Microbiology Reviews Dec 2021Infections due to species are an acute threat to human health; members of the section are the most frequently occurring agents, but depending on the local... (Review)
Review
Infections due to species are an acute threat to human health; members of the section are the most frequently occurring agents, but depending on the local epidemiology, representatives of section or section are the second or third most important. species complex is of great interest, as it is usually amphotericin B resistant and displays notable differences in immune interactions in comparison to . The latest epidemiological surveys show an increased incidence of as well as an expanding clinical spectrum (chronic infections) and new groups of at-risk patients being affected. Hallmarks of these non- invasive mold infections are high potential for tissue invasion, dissemination, and possible morbidity due to mycotoxin production. We seek to review the microbiology, epidemiology, and pathogenesis of species complex, address clinical characteristics, and highlight the underlying mechanisms of amphotericin B resistance. Selected topics will contrast key elements of with . We provide a comprehensive resource for clinicians dealing with fungal infections and researchers working on pathogenesis, aiming to bridge the emerging translational knowledge and future therapeutic challenges on this opportunistic pathogen.
Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Aspergillus fumigatus; Humans; Microbial Sensitivity Tests
PubMed: 34190571
DOI: 10.1128/CMR.00311-20 -
Genes Nov 2020, , and species are the most frequent cause of severe human fungal infections. Clinically relevant antifungal drugs are scarce, and their effectiveness are hampered by... (Review)
Review
, , and species are the most frequent cause of severe human fungal infections. Clinically relevant antifungal drugs are scarce, and their effectiveness are hampered by the ability of fungal cells to develop drug resistance mechanisms. Drug effectiveness and drug resistance in human pathogens is very often affected by their "transportome". Many studies have covered a panoply of drug resistance mechanisms that depend on drug efflux pumps belonging to the ATP-Binding Cassette and Major Facilitator Superfamily. However, the study of drug uptake mechanisms has been, to some extent, overlooked in pathogenic fungi. This review focuses on discussing current knowledge on drug uptake systems in fungal pathogens, highlighting the need for further studies on this topic of great importance. The following subjects are covered: (i) drugs imported by known transporter(s) in pathogenic fungi; and (ii) drugs imported by known transporter(s) in the model yeast or in human parasites, aimed at the identification of their homologs in pathogenic fungi. Besides its contribution to increase the understanding of drug-pathogen interactions, the practical implications of identifying drug importers in human pathogens are discussed, particularly focusing on drug development strategies.
Topics: ATP-Binding Cassette Transporters; Antifungal Agents; Aspergillus; Biological Transport; Candida albicans; Drug Carriers; Drug Resistance, Fungal; Fungi; Membrane Transport Proteins; Mycoses; Saccharomyces cerevisiae
PubMed: 33182427
DOI: 10.3390/genes11111324 -
Revista Chilena de Infectologia :... Aug 2019
Topics: Anti-Bacterial Agents; Aspergillus
PubMed: 31859778
DOI: 10.4067/S0716-10182019000400521 -
Medical Mycology Journal 2023Aspergillus species have been identified morphologically in most clinical laboratories without conducting antifungal susceptibility tests (ASTs). This review aimed to... (Review)
Review
Aspergillus species have been identified morphologically in most clinical laboratories without conducting antifungal susceptibility tests (ASTs). This review aimed to evaluate the importance of accurate identification and ASTs of Aspergillus spp. strains for adequate clinical management of Aspergillus infections. The Aspergillus spp. were identified by gene sequencing, and ASTs for itraconazole and voriconazole were conducted. In Aspergillus section Nigri, the rate of detection of cryptic species was high, and Aspergillus tubingensis with lower susceptibility to azoles was frequently identified. Azole-resistant Aspergillus fumigatus was detected at a high rate in patients with chronic pulmonary aspergillosis managed with long-term azole treatment. In conclusion, accurate identification of Aspergillus spp. and ASTs are needed to carry out appropriate treatment. Moreover, we hope that these microbiological tests will be widely used in clinical laboratories to improve clinical practice.
Topics: Humans; Antifungal Agents; Drug Resistance, Fungal; Microbial Sensitivity Tests; Aspergillus; Aspergillus fumigatus; Azoles; Fungal Proteins
PubMed: 38030277
DOI: 10.3314/mmj.23-004 -
Marine Drugs Apr 2023Secondary metabolites from marine organisms are diverse in structure and function. Marine is an important source of bioactive natural products. We reviewed the... (Review)
Review
Secondary metabolites from marine organisms are diverse in structure and function. Marine is an important source of bioactive natural products. We reviewed the structures and antimicrobial activities of compounds isolated from different marine over the past two years (January 2021-March 2023). Ninety-eight compounds derived from species were described. The chemical diversity and antimicrobial activities of these metabolites will provide a large number of promising lead compounds for the development of antimicrobial agents.
Topics: Anti-Infective Agents; Aspergillus; Aquatic Organisms; Biological Products
PubMed: 37233471
DOI: 10.3390/md21050277 -
Journal of Molecular Biology Oct 2019The genus Aspergillus is ubiquitous in the environment and contains a number of species, primarily A. fumigatus, that cause mold-associated disease in humans. Humans... (Review)
Review
The genus Aspergillus is ubiquitous in the environment and contains a number of species, primarily A. fumigatus, that cause mold-associated disease in humans. Humans inhale several hundred to several thousand Aspergillus conidia (i.e., vegetative spores) daily and typically clear these in an asymptomatic manner. In immunocompromised individuals, Aspergillus conidia can germinate into tissue-invasive hyphae, disseminate, and cause invasive aspergillosis. In this review, we first discuss novel concepts in host defense against Aspergillus infections and emphasize new insights in fungal recognition and signaling, innate immune activation, and fungal killing. Second, the review focuses on novel concepts of Aspergillus pathogenesis and highlights emerging knowledge regarding fungal strain heterogeneity, stress responses, and metabolic adaptations on infectious outcomes. Mechanistic insight into the host-pathogen interplay is thus critical to define novel druggable fungal targets and to exploit novel immune-based strategies to improve clinical outcomes associated with aspergillosis in vulnerable patient populations.
Topics: Animals; Aspergillosis; Aspergillus; Cell Wall; Humans; Immunity, Innate; Mycology
PubMed: 30954573
DOI: 10.1016/j.jmb.2019.03.027 -
Molecules (Basel, Switzerland) Jan 2021Marine fungi produce many halogenated metabolites with a variety of structures, from acyclic entities with a simple linear chain to multifaceted polycyclic molecules.... (Review)
Review
Marine fungi produce many halogenated metabolites with a variety of structures, from acyclic entities with a simple linear chain to multifaceted polycyclic molecules. Over the past few decades, their pharmaceutical and medical application have been explored and still the door is kept open due to the need of new drugs from relatively underexplored sources. Biological properties of halogenated compounds such as anticancer, antiviral, antibacterial, anti-inflammatory, antifungal, antifouling, and insecticidal activity have been investigated. This review describes the chemical structures and biological activities of 217 halogenated compounds derived mainly from and marine fungal strains reported from 1994 to 2019.
Topics: Aquatic Organisms; Aspergillus; Hydrocarbons, Halogenated; Penicillium
PubMed: 33467200
DOI: 10.3390/molecules26020458 -
Microbiology Spectrum Sep 2021The ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), first...
The ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), first described in Wuhan, China. A subset of COVID-19 patients has been reported to have acquired secondary infections by microbial pathogens, such as opportunistic fungal pathogens from the genus Aspergillus. To gain insight into COVID-19-associated pulmonary aspergillosis (CAPA), we analyzed the genomes and characterized the phenotypic profiles of four CAPA isolates of Aspergillus fumigatus obtained from patients treated in the area of North Rhine-Westphalia, Germany. By examining the mutational spectrum of single nucleotide polymorphisms, insertion-deletion polymorphisms, and copy number variants among 206 genes known to modulate A. fumigatus virulence, we found that CAPA isolate genomes do not exhibit significant differences from the genome of the Af293 reference strain. By examining a number of factors, including virulence in an invertebrate moth model, growth in the presence of osmotic, cell wall, and oxidative stressors, secondary metabolite biosynthesis, and the MIC of antifungal drugs, we found that CAPA isolates were generally, but not always, similar to A. fumigatus reference strains Af293 and CEA17. Notably, CAPA isolate D had more putative loss-of-function mutations in genes known to increase virulence when deleted. Moreover, CAPA isolate D was significantly more virulent than the other three CAPA isolates and the A. fumigatus reference strains Af293 and CEA17, but similarly virulent to two other clinical strains of A. fumigatus. These findings expand our understanding of the genomic and phenotypic characteristics of isolates that cause CAPA. The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), has already killed millions of people. COVID-19 patient outcome can be further complicated by secondary infections, such as COVID-19-associated pulmonary aspergillosis (CAPA). CAPA is caused by Aspergillus fungal pathogens, but there is little information about the genomic and phenotypic characteristics of CAPA isolates. We conducted genome sequencing and extensive phenotyping of four CAPA isolates of Aspergillus fumigatus from Germany. We found that CAPA isolates were often, but not always, similar to other reference strains of A. fumigatus across 206 genetic determinants of infection-relevant phenotypes, including virulence. For example, CAPA isolate D was more virulent than other CAPA isolates and reference strains in an invertebrate model of fungal disease, but similarly virulent to two other clinical strains. These results expand our understanding of COVID-19-associated pulmonary aspergillosis.
Topics: Aged; Antifungal Agents; Aspergillus; Aspergillus fumigatus; COVID-19; Female; Genomics; Humans; Male; Metabolomics; Microbial Sensitivity Tests; Middle Aged; Mutation; Phenotype; Polymorphism, Single Nucleotide; Pulmonary Aspergillosis; SARS-CoV-2; Secondary Metabolism; Virulence
PubMed: 34106569
DOI: 10.1128/Spectrum.00010-21