-
Clinical Microbiology and Infection :... Mar 2013Mycotic keratitis (an infection of the cornea) is an important ocular infection, especially in young male outdoor workers. There are two frequent presentations:... (Review)
Review
Mycotic keratitis (an infection of the cornea) is an important ocular infection, especially in young male outdoor workers. There are two frequent presentations: keratitis due to filamentous fungi (Fusarium, Aspergillus, phaeohyphomycetes and Scedosporium apiospermum are frequent causes) and keratitis due to yeast-like fungi (Candida albicans and other Candida species). In the former, trauma is usually the sole predisposing factor, although previous use of corticosteroids and contact lens wear are gaining importance as risk factors; in the latter, there is usually some systemic or local (ocular) defect. The clinical presentation and clinical features may suggest a diagnosis of mycotic keratitis; increasingly, in vivo (non-invasive) imaging techniques (confocal microscopy and anterior segment optical coherence tomography) are also being used for diagnosis. However, microbiological investigations, particularly direct microscopic examination and culture of corneal scrape or biopsy material, still form the cornerstone of diagnosis. In recent years, the PCR has gained prominence as a diagnostic aid for mycotic keratitis, being used to complement microbiological methods; more importantly, this molecular method permits rapid specific identification of the aetiological agent. Although various antifungal compounds have been used for therapy, management of this condition (particularly if deep lesions occur) continues to be problematic; topical natamycin and, increasingly, voriconazole (given by various routes) are key therapeutic agents. Therapeutic surgery, such as therapeutic penetrating keratoplasty, is needed when medical therapy fails. Increased awareness of the importance of this condition is likely to spur future research initiatives.
Topics: Antifungal Agents; Clinical Laboratory Techniques; Debridement; Fungi; Humans; Immunocompromised Host; Keratitis; Mycoses; Wounds and Injuries
PubMed: 23398543
DOI: 10.1111/1469-0691.12126 -
Journal of Fungi (Basel, Switzerland) Oct 2020Fosmanogepix is a first-in-class antifungal currently in Phase 2 clinical trials for the treatment of invasive fungal infections caused by and rare molds. Fosmanogepix... (Review)
Review
Fosmanogepix is a first-in-class antifungal currently in Phase 2 clinical trials for the treatment of invasive fungal infections caused by and rare molds. Fosmanogepix is the N-phosphonooxymethylene prodrug of manogepix, an inhibitor of the fungal enzyme Gwt1. Manogepix demonstrates broad spectrum in vitro activity against yeasts and molds, including difficult to treat pathogens. Because of its novel mechanism of action, manogepix retains potency against many resistant strains including echinocandin-resistant and azole-resistant Manogepix is also active against pathogens that demonstrate intrinsic resistance to other drug classes, such as , and with variable activity against Mucorales. Fosmanogepix demonstrates significant in vivo efficacy in mouse and rabbit disseminated infection models due to and as well as pulmonary infection models of and Clinical trials demonstrated high oral bioavailability (>90%), enabling switching between fosmanogepix intravenous and oral formulations without compromising blood levels. Favorable drug-drug interaction, tolerability, and wide tissue distribution profiles are observed making fosmanogepix an attractive option for the treatment of invasive fungal infections. This systematic review summarizes the findings of published data on fosmanogepix.
PubMed: 33105672
DOI: 10.3390/jof6040239 -
Clinical Microbiology and Infection :... Apr 2014Mycoses summarized in the hyalohyphomycosis group are heterogeneous, defined by the presence of hyaline (non-dematiaceous) hyphae. The number of organisms implicated in...
Mycoses summarized in the hyalohyphomycosis group are heterogeneous, defined by the presence of hyaline (non-dematiaceous) hyphae. The number of organisms implicated in hyalohyphomycosis is increasing and the most clinically important species belong to the genera Fusarium, Scedosporium, Acremonium, Scopulariopsis, Purpureocillium and Paecilomyces. Severely immunocompromised patients are particularly vulnerable to infection, and clinical manifestations range from colonization to chronic localized lesions to acute invasive and/or disseminated diseases. Diagnosis usually requires isolation and identification of the infecting pathogen. A poor prognosis is associated with fusariosis and early therapy of localized disease is important to prevent progression to a more aggressive or disseminated infection. Therapy should include voriconazole and surgical debridement where possible or posaconazole as salvage treatment. Voriconazole represents the first-line treatment of infections due to members of the genus Scedosporium. For Acremonium spp., Scopulariopsis spp., Purpureocillium spp. and Paecilomyces spp. the optimal antifungal treatment has not been established. Management usually consists of surgery and antifungal treatment, depending on the clinical presentation.
Topics: Antifungal Agents; Fusarium; Humans; Hyalohyphomycosis; Scedosporium
PubMed: 24548001
DOI: 10.1111/1469-0691.12465 -
Medical Hypothesis, Discovery &... 2021(SA) is commonly present in temperate climates. It can induce cutaneous and subcutaneous tissue infections as well as disseminated infections in immunocompromised or... (Review)
Review
BACKGROUND
(SA) is commonly present in temperate climates. It can induce cutaneous and subcutaneous tissue infections as well as disseminated infections in immunocompromised or immunocompetent hosts. The eye is rarely involved. Keratomycosis is usually caused by plant-related injuries. Here, we describe a patient with a severe and sight-threatening corneal abscess caused by SA, which was associated with contact lens wear and was successfully treated with a combination of surgical and medical therapies.
CASE PRESENTATION
An otherwise healthy 22-year-old woman, with history of contact lens wearing, was referred to the Ophthalmic Department of Bari University, Bari, Italy for evaluation of a corneal abscess and hypopyon in her left eye. Intensive topical and systemic antibiotic therapy was initiated after obtaining con- junctival swabs. Within 2 days, her ophthalmic condition had worsened, and her best-corrected visual acuity (BCVA) dropped to counting fingers. She underwent penetrating keratoplasty, after which her ophthalmic condition improved. Microbiological culture, obtained from the explanted cornea, revealed SA infection. This was addressed with specific topical and systemic therapy using voriconazole. Two weeks later, the con- dition of her left eye was stable, with mild corneal edema and no sign of acute graft rejection. Her BCVA improved to 20/25, and all medications were discontinued, except for the steroid eye drop. The patient was scheduled for a 1-month follow-up.
CONCLUSIONS
Prompt identification of the etiological agent is mandatory to perform appropriate therapy in cases of keratomycosis. Surgery to remove the infected cornea is helpful in patients with deteriorating condition, in whom the initial medical therapy has failed. Topical and systemic antimycotic therapy, based on microbiological culture, is recommended as an adjunctive therapy for the surgical management of severe corneal mycotic abscesses.
PubMed: 37641616
DOI: 10.51329/mehdiophthal1425 -
Scientific Reports Feb 2019The opportunistic pathogen Mycobacterium ulcerans, which is responsible for Buruli ulcer, synthesizes a series of plasmid-encoded macrolide exotoxins termed...
The opportunistic pathogen Mycobacterium ulcerans, which is responsible for Buruli ulcer, synthesizes a series of plasmid-encoded macrolide exotoxins termed mycolactones. These toxins destabilize cell membranes and induce apoptosis-associated pleiotropic effects including tissue destruction, analgesic and anti-inflammatory effects. Despite its medical interest, M. ulcerans is primarily an environmental mycobacterium and the primary functions of mycolactones in the natural ecosystems are unknown. High throughput biochemical profiling findings suggested that M. ulcerans may interact with fungi. Here, we report that semi-purified and purified mycolactones significantly enhance spore germination of Scedosporium apiospermum, Fusarium equiseti and Mucor circinelloides; and that M. ulcerans mycolactones significantly attract colonies of M. circinelloides whereas no significant effect was observed on S. apiospermum and F. equiseti. These experimental results suggest that mycolactones exhibit a chemoattractant activity independent of their cytotoxicity. In natural ecosystems, M. ulcerans mycolactones may act as spore germination inducers and chemoattractants for some fungi, suggesting a novel role for this unique class of mycobacterial toxins in natural ecosystems.
Topics: Apoptosis; Ecosystem; Exotoxins; Fungi; Humans; Macrolides; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans
PubMed: 30816261
DOI: 10.1038/s41598-019-39927-3 -
Frontiers in Cellular and Infection... 2021and species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising...
and species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising conditions. Because they are usually resistant to many antifungal drugs available in clinical settings, studies of alternative targets in fungal cells and therapeutic approaches are necessary. In the present work, we evaluated the antifungal activity of miltefosine against and species and how this phospholipid analogue affects the fungal cell. Miltefosine inhibited different and species at 2-4 µg/ml and reduced biofilm formation. The loss of membrane integrity in caused by miltefosine was demonstrated by leakage of intracellular components and lipid raft disorganisation. The exogenous addition of glucosylceramide decreased the inhibitory activity of miltefosine. Reactive oxygen species production and mitochondrial activity were also affected by miltefosine, as well as the susceptibility to fluconazole, caspofungin and myoricin. The data obtained in the present study contribute to clarify the dynamics of the interaction between miltefosine and and cells, highlighting its potential use as new antifungal drug in the future.
Topics: Antifungal Agents; Ascomycota; Humans; Microbial Sensitivity Tests; Phosphorylcholine; Scedosporium
PubMed: 34368017
DOI: 10.3389/fcimb.2021.698662 -
Journal of Fungi (Basel, Switzerland) Jan 2021Infections caused by the opportunistic pathogens / are on the rise. This causes problems in the clinic due to the difficulty in diagnosing and treating them. This review... (Review)
Review
Infections caused by the opportunistic pathogens / are on the rise. This causes problems in the clinic due to the difficulty in diagnosing and treating them. This review collates information published on immune response against these fungi, since an understanding of the mechanisms involved is of great interest in developing more effective strategies against them. / cell wall components, including peptidorhamnomannans (PRMs), α-glucans and glucosylceramides, are important immune response activators following their recognition by TLR2, TLR4 and Dectin-1 and through receptors that are yet unknown. After recognition, cytokine synthesis and antifungal activity of different phagocytes and epithelial cells is species-specific, highlighting the poor response by microglial cells against . Moreover, a great number of / antigens have been identified, most notably catalase, PRM and Hsp70 for their potential medical applicability. Against host immune response, these fungi contain evasion mechanisms, inducing host non-protective response, masking fungal molecular patterns, destructing host defense proteins and decreasing oxidative killing. In conclusion, although many advances have been made, many aspects remain to be elucidated and more research is necessary to shed light on the immune response to /.
PubMed: 33499053
DOI: 10.3390/jof7020075 -
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 -
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 -
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