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European Respiratory Review : An... Dec 2022Non- filamentous fungi causing invasive mould infections have increased over the last years due to the widespread use of anti- prophylaxis and increased complexity and...
Non- filamentous fungi causing invasive mould infections have increased over the last years due to the widespread use of anti- prophylaxis and increased complexity and survival of immunosuppressed patients. In the few studies that have reported on invasive mould infection epidemiology, Mucorales are the most frequently isolated group, followed by either spp. or spp. The overall incidence is low, but related mortality is exceedingly high. Patients with haematological malignancies and haematopoietic stem cell transplant recipients comprise the classical groups at risk of infection for non- moulds due to profound immunosuppression and the vast use of anti- prophylaxis. Solid organ transplant recipients also face a high risk, especially those receiving lung transplants, due to direct exposure of the graft to mould spores with altered mechanical and immunological elimination, and intense, associated immunosuppression. Diagnosing non- moulds is challenging due to unspecific symptoms and radiological findings, lack of specific biomarkers, and low sensitivity of cultures. However, the advent of molecular techniques may prove helpful. Mucormycosis, fusariosis and scedosporiosis hold some differences regarding clinical paradigmatic presentations and preferred antifungal therapy. Surgery might be an option, especially in mucormycosis. Finally, various promising strategies to restore or enhance the host immune response are under current evaluation.
Topics: Humans; Mucormycosis; Antifungal Agents; Fungi; Biomarkers; Lung
PubMed: 36261156
DOI: 10.1183/16000617.0104-2022 -
IMA Fungus Dec 2023Emerging fungal pathogens are a global challenge for humankind. Many efforts have been made to understand the mechanisms underlying pathogenicity in bacteria, and OMICs...
Emerging fungal pathogens are a global challenge for humankind. Many efforts have been made to understand the mechanisms underlying pathogenicity in bacteria, and OMICs techniques are largely responsible for those advancements. By contrast, our limited understanding of opportunism and antifungal resistance is preventing us from identifying, limiting and interpreting the emergence of fungal pathogens. The genus Scedosporium (Microascaceae) includes fungi with high tolerance to environmental pollution, whilst some species can be considered major human pathogens, such as Scedosporium apiospermum and Scedosporium boydii. However, unlike other fungal pathogens, little is known about the genome evolution of these organisms. We sequenced two novel genomes of Scedosporium aurantiacum and Scedosporium minutisporum isolated from extreme, strongly anthropized environments. We compared all the available Scedosporium and Microascaceae genomes, that we systematically annotated and characterized ex novo in most cases. The genomes in this family were integrated in a Phylum-level comparison to infer the presence of putative, shared genomic traits in filamentous ascomycetes with pathogenic potential. The analysis included the genomes of 100 environmental and clinical fungi, revealing poor evolutionary convergence of putative pathogenicity traits. By contrast, several features in Microascaceae and Scedosporium were detected that might have a dual role in responding to environmental challenges and allowing colonization of the human body, including chitin, melanin and other cell wall related genes, proteases, glutaredoxins and magnesium transporters. We found these gene families to be impacted by expansions, orthologous transposon insertions, and point mutations. With RNA-seq, we demonstrated that most of these anciently impacted genomic features responded to the stress imposed by an antifungal compound (voriconazole) in the two environmental strains S. aurantiacum MUT6114 and S. minutisporum MUT6113. Therefore, the present genomics and transcriptomics investigation stands on the edge between stress resistance and pathogenic potential, to elucidate whether fungi were pre-adapted to infect humans. We highlight the strengths and limitations of genomics applied to opportunistic human pathogens, the multifactoriality of pathogenicity and resistance to drugs, and suggest a scenario where pressures other than anthropic contributed to forge filamentous human pathogens.
PubMed: 38049914
DOI: 10.1186/s43008-023-00128-3 -
American Journal of Clinical Pathology Nov 2021To further characterize the histomorphology and clinicopathologic features of colonization and invasive disease by Scedosporium and Lomentospora.
OBJECTIVE
To further characterize the histomorphology and clinicopathologic features of colonization and invasive disease by Scedosporium and Lomentospora.
METHODS
We conducted a 20-year retrospective study. Patients with at least 1 histopathology specimen and concurrent culture were included. Clinical features, histopathology, microbiology, and outcomes were analyzed.
RESULTS
Eighteen patients were identified, and all were immunocompromised. Eight patients had colonization, while 10 had invasive disease (pneumonia [n = 3], skin and soft-tissue infections [n = 3], disseminated disease [n = 4]). Scedosporium apiospermum was identified in 15 patients, Lomentospora prolificans in 2 patients, and Scedosporium ellipsoideum in 1 patient. Fungal elements were identified histologically in 11 patients. Granulomatous, suppurative, and necrotizing inflammation with irregular branching hyphae and characteristic microconidia were observed in 9 cases; conidiogenous cells were identified in 4 cases. Seven patients died of invasive disease despite therapy, and 3 recovered after treatment. No deaths were observed in patients with colonization.
CONCLUSIONS
Scedosporium and Lomentospora are rare, virulent opportunistic fungal pathogens. Fungal morphology may overlap with other hyaline molds, but identification of obovoid conidia should allow a diagnosis of non-Aspergillus hyalohyphomycosis and consideration of Scedosporium and Lomentospora. Histopathologic correlation with culture and polymerase chain reaction is critical for diagnosis and treatment.
Topics: Antifungal Agents; Humans; Hyphae; Immunocompromised Host; Retrospective Studies; Scedosporium
PubMed: 34160012
DOI: 10.1093/ajcp/aqab070 -
Journal of Fungi (Basel, Switzerland) Jan 2023species are usually soil saprophytes but some members of the genus such as and have been regularly reported as causing human respiratory infections, particularly in...
species are usually soil saprophytes but some members of the genus such as and have been regularly reported as causing human respiratory infections, particularly in patients with cystic fibrosis (CF). Because of their low sensitivity to almost all available antifungal drugs, a better understanding of the pathogenic mechanisms of these fungi is mandatory. Likewise, identification of the origin of the contamination of patients with CF may be helpful to propose prophylactic measures. In this aim, environmental studies were conducted demonstrating that species are abundant in human-made environments and associated with nutrient-rich substrates. Although their natural habitat remains unknown, there is accumulated evidence to consider them as wood-decaying fungi. This study aimed to demonstrate the ability of these fungi to utilize lignocellulose compounds, especially lignin, as a carbon source. First, the lignolytic properties of species were confirmed by cultural methods, and biochemical assays suggested the involvement of peroxidases and oxidases as lignin-modifying enzymes. genomes were then screened using tBLASTn searches. Fifteen candidate genes were identified, including four peroxidase and seven oxidase genes, and some of them were shown, by real-time PCR experiments, to be overexpressed in lignin-containing medium, thus confirming their involvement in lignin degradation.
PubMed: 36675925
DOI: 10.3390/jof9010105 -
Medical Mycology Apr 2023Scedosporium and Lomentospora are important opportunistic pathogens causing localized or disseminated infection in humans. Understanding their environmental distribution...
Scedosporium and Lomentospora are important opportunistic pathogens causing localized or disseminated infection in humans. Understanding their environmental distribution is critical for public hygiene and clinical management. We carried out the first environmental survey in urbanized and natural regions in Taiwan. Overall, Scedosporium and Lomentospora species were recovered in 132 out of 273 soil samples (48.4%) across Taiwan. We morphologically and molecularly identified six Scedosporium and one Lomentospora species. All four major clinical relevant species were isolated with high frequency, i.e., Scedosporium apiospermum (42.4%), S. boydii (21.8%), Lomentosporaprolificans (14.5%), S. aurantiacum (8.5%); two clinically minor species, Pseudallescheria angusta (6.7%) and S. dehoogii (5.6%), and a saprobic species, S. haikouense (0.6%), had moderate to rare incidence. These fungal species had high incidence in urban (48.6%) and hospital (67.4%) soil samples, and had limited distribution in samples from natural regions (5%). Multivariate analysis of the fungal composition revealed strong evidence of the preferential distribution of these fungi in urban and hospital regions compared with natural sites. In addition, strong evidence suggested that the distribution and abundance of these fungal species were highly heterogeneous in the environment; samples in vicinity often yielded varied fungal communities. We concluded that these fungal species were prevalent in soil in Taiwan and their occurrences were associated with human activities. Although, hygiene sensitive sites such as hospitals were not harboring heavier fungal burdens than other urban facilities in our survey, still, aware should be taken for the high frequency of these clinical relevant species around hospital regions.
Topics: Animals; Humans; Scedosporium; Prevalence; Taiwan; Mycoses
PubMed: 37061781
DOI: 10.1093/mmy/myad041 -
Journal of Fungi (Basel, Switzerland) Jan 2021/ fungi are increasingly recognized pathogens. As these fungi are resistant to many antifungal agents, early diagnosis is essential for initiating targeted drug therapy.... (Review)
Review
/ fungi are increasingly recognized pathogens. As these fungi are resistant to many antifungal agents, early diagnosis is essential for initiating targeted drug therapy. Here, we review the microbiological tools for the detection and diagnosis of invasive scedosporiosis and lomentosporiosis. Of over 10 species, , , and cause the majority of infections. Definitive diagnosis relies on one or more of visualization, isolation or detection of the fungus from clinical specimens by microscopy techniques, culture and molecular methods such as panfungal PCR or genus-/species-specific multiplex PCR. For isolation from respiratory tract specimens, selective media have shown improved isolation rates. Species identification is achieved by macroscopic and microscopic examination of colonies, but species should be confirmed by ITS with or without β-tubulin gene sequencing or other molecular methods. Matrix-assisted laser desorption ionization-time of flight mass spectrometry databases are improving but may need supplementation by in-house spectra for species identification. Reference broth microdilution methods is preferred for antifungal susceptibility testing. Next-generation sequencing technologies have good potential for characterization of these pathogens. Diagnosis of / infections relies on multiple approaches encompassing both phenotypic- and molecular-based methods.
PubMed: 33406673
DOI: 10.3390/jof7010023 -
Frontiers in Microbiology 2021Lignin, a natural polyaromatic macromolecule, represents an essential component of the lignocellulose biomass. Due to its complexity, the natural degradation of this...
Lignin, a natural polyaromatic macromolecule, represents an essential component of the lignocellulose biomass. Due to its complexity, the natural degradation of this molecule by microorganisms still remains largely misunderstood. Extracellular oxidative degradation is followed by intracellular metabolic degradation of conserved aromatic intermediate compounds (protocatechuate, catechol, hydroxyquinol, and gentisic acid) that are used as carbon and energy sources. The lower funneling pathways are characterized by the opening of the aromatic ring of these molecules through dioxygenases, leading to degradation products that finally enter into the tricarboxylic acid (TCA) cycle. In order to better understand the adaptation mechanisms of species to their environment, these specific catabolism pathways were studied. Genes encoding ring-cleaving dioxygenases were identified in genomes by sequence homology, and a bioinformatic analysis of the organization of the corresponding gene clusters was performed. In addition, these predictions were confirmed by evaluation of the expression level of the genes of the gentisic acid cluster. When the fungus was cultivated in the presence of lignin or gentisic acid as sole carbon source, experiments revealed that the genes of the gentisic acid cluster were markedly overexpressed in the two species analyzed ( and ). Only the gene encoding a membrane transporter was not overexpressed in the gentisic acid-containing medium. Together, these data suggest the involvement of the lower funneling pathways in adaptation to their environment.
PubMed: 34276578
DOI: 10.3389/fmicb.2021.630753 -
Brazilian Journal of Microbiology :... Jun 2020Scedosporium spp. and Lomentospora prolificans are filamentous fungi that emerged as human pathogens; however, their mechanisms of virulence/pathogenesis are still...
Scedosporium spp. and Lomentospora prolificans are filamentous fungi that emerged as human pathogens; however, their mechanisms of virulence/pathogenesis are still largely unknown. In the present work, we have evaluated the interaction of S. apiospermum, S. minutisporum, S. aurantiacum, and L. prolificans with lung epithelial cells (A549 line). The results showed that conidia were able to interact with A549 cells, displaying association indexes of 73.20, 117.98, 188.01, and 241.63 regarding S. apiospermum, L. prolificans, S. minutisporum, and S. aurantiacum, respectively. Light microscopy images evidenced morphological changes in epithelial cells, including rounding and detachment, especially during the interaction with L. prolificans. Plasma membrane injuries were detected in A549 cells after 1 h of co-culturing with S. aurantiacum and S. minutisporum and after 4 h with S. apiospermum and L. prolificans, as judged by the passive incorporation of propidium iodide. After 24 h of fungi-epithelial cells interaction, only mycelia were observed covering the A549 monolayer. Interestingly, the mycelial trap induced severe damage in the A549 cells, culminating in epithelial cell death. Our results demonstrate some relevant events that occur during the contact between lung epithelial cells and Scedosporium/Lomentospora species, including conidial adhesion and hyphal growth with consequent irreversible injury on A549 cells, adding light to the infection process caused by these opportunistic and multidrug-resistant fungi.
Topics: A549 Cells; Epithelial Cells; Host-Pathogen Interactions; Humans; Lung; Scedosporium; Spores, Fungal; Virulence
PubMed: 31736016
DOI: 10.1007/s42770-019-00183-2 -
Acta Tropica Jan 2022Mycetoma is a chronic granulomatous inflammatory disease that is caused either by bacteria or fungi. Bacterial mycetoma (actinomycetoma) can be caused by various... (Review)
Review
Mycetoma is a chronic granulomatous inflammatory disease that is caused either by bacteria or fungi. Bacterial mycetoma (actinomycetoma) can be caused by various causative agents of the genera Nocardia, Streptomyces and Actinomadura. On the other hand, fungal mycetoma (eumycetoma) is most commonly caused by causative agents belonging to the genera Madurella, Scedosporium and Falciformispora. Early and accurate diagnosis of the causative organisms can guide proper patient management and treatment. To allow rapid and accurate species identification, different molecular techniques were developed over the past decades. These techniques can be protein based (MALDI-TOF MS) as well as DNA based (Sequencing, PCR and isothermal amplification methods). In this review, we provide an overview of the different molecular techniques currently in use and identify knowledge gaps, which need to be addressed before we can implement molecular diagnostics for mycetoma in different clinical settings.
Topics: Fungi; Humans; Madurella; Mycetoma; Polymerase Chain Reaction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 34687643
DOI: 10.1016/j.actatropica.2021.106205 -
Pathogens (Basel, Switzerland) May 2023Fungal infections are a significant source of morbidity in the lung transplant population via direct allograft damage and predisposing patients to the development of... (Review)
Review
Fungal infections are a significant source of morbidity in the lung transplant population via direct allograft damage and predisposing patients to the development of chronic lung allograft dysfunction. Prompt diagnosis and treatment are imperative to limit allograft damage. This review article discusses incidence, risk factors, and symptoms with a specific focus on diagnostic and treatment strategies in the lung transplant population for fungal infections caused by , , , , , , , and . Evidence for the use of newer triazole and inhaled antifungals to treat isolated pulmonary fungal infections in lung transplant recipients is also discussed.
PubMed: 37242364
DOI: 10.3390/pathogens12050694