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Journal of Medical Virology Jan 2022A severe pandemic of Coronavirus Disease (COVID-19) has been sweeping the globe since 2019, and this time, it did not stop, with frequent mutations transforming into...
A severe pandemic of Coronavirus Disease (COVID-19) has been sweeping the globe since 2019, and this time, it did not stop, with frequent mutations transforming into virulent strains, for instance, B.1.1.7, B.1.351, and B.1.427. In recent months, a fungal infection, mucormycosis has emerged with more fatal responses and significantly increased mortality rate. To measure the severity and potential alternative approaches against black fungus coinfection in COVID-19 patients, PubMed, Google Scholar, World Health Organization (WHO) newsletters, and other online resources, based on the cases reported and retrospective observational analysis were searched from the years 2015-2021. The studies reporting mucormycosis with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coinfection and/or demonstrating potential risk factors, such as a history of diabetes mellitus or suppressed immune system were included, and reports published in non-English language were excluded. More than 20 case reports and observational studies on black fungus coinfection in COVID-19 patients were eligible for inclusion. The results indicated that diabetes mellitus, hyperglycemic, and immunocompromised COVID-19 patients with mucormycosis were at a higher risk. We found that it was prudent to assess the potential risk factors and severity of invasive mycosis via standardized diagnostic and clinical settings. Large-scale studies need to be conducted to identify early biomarkers and optimization of diagnostic methods has to be established per population and geographical variation. This will not only help clinicians around the world to detect the coinfection in time but also will prepare them for future outbreaks of other potential pandemics.
Topics: COVID-19; Coinfection; Diabetes Mellitus; Humans; Hyperglycemia; Immunocompromised Host; Mucorales; Mucormycosis; Retrospective Studies; Risk Factors; SARS-CoV-2
PubMed: 34570905
DOI: 10.1002/jmv.27358 -
Revista Iberoamericana de Micologia 2021Infections caused by mucorales, with an increasing incidence after candidiasis and aspergillosis, are characterized by the fast angioinvasion of blood vessels and...
Infections caused by mucorales, with an increasing incidence after candidiasis and aspergillosis, are characterized by the fast angioinvasion of blood vessels and invasion of neighboring organs or structures. Mucorales most commonly cause rhinocerebral, pulmonary, cutaneous, digestive or disseminated infections, and their spread is favored by certain underlying diseases (diabetes, kidney failure) and risk factors (neutropenia, immunosuppression, iron overload). These infections have a high mortality rate, over 40% in many series, and the key to their cure depends on both an early diagnosis and an antifungal treatment, associated in most cases with extensive surgical debridement and other adjunctive therapies. Currently, there are international guidelines, not only local ones, for the management of mucormycosis, in which it is considered by consensus and with a strong recommendation that first-line treatment with high-dose liposomal amphotericin B is the best choice. The combined antifungal treatment of polyene agents with triazoles or candins remains in open debate.
Topics: Antifungal Agents; Aspergillosis; Humans; Mucorales; Mucormycosis; Triazoles
PubMed: 34144835
DOI: 10.1016/j.riam.2021.04.003 -
Clinical Microbiology and Infection :... Oct 2009A definitive diagnosis of zygomycosis caused by Mucorales can be made by histopathological examination with or without isolation of the fungus from the same site.... (Review)
Review
A definitive diagnosis of zygomycosis caused by Mucorales can be made by histopathological examination with or without isolation of the fungus from the same site. Histopathological examination of the tissues affected typically shows characteristic broad, hyaline, ribbon-like, irregular fungal hyphae with wide-angle branching, accompanied by tissue necrosis and angioinvasion of the fungi. Tissue invasion by the fungal hyphae as seen by microscopy is essential to establish the diagnosis. Fungal elements can be stained with Gomori methenamine-silver, periodic acid-Schiff or Calcoflour white stain. All Mucorales grow rapidly on most fungal media such as Sabouraud dextrose agar incubated at 25-30 degrees C. Mucorales from a sterile site or repeated positive cultures of the fungi from a non-sterile site are considered significant in a high-risk patient with predisposing factors for acquisition of zygomycosis. Positive cultures from non-sterile specimens should be interpreted with caution and will require correlation between the finding and the clinical situation.
Topics: Clinical Laboratory Techniques; Culture Media; Histocytochemistry; Humans; Mucorales; Mucormycosis; Staining and Labeling
PubMed: 19754760
DOI: 10.1111/j.1469-0691.2009.02999.x -
Journal of Clinical Microbiology Apr 2011Rapid detection and differentiation of Aspergillus and Mucorales species in fungal rhinosinusitis diagnosis are desirable, since the clinical management and prognosis...
Rapid detection and differentiation of Aspergillus and Mucorales species in fungal rhinosinusitis diagnosis are desirable, since the clinical management and prognosis associated with the two taxa are fundamentally different. We describe an assay based on a combination of broad-range PCR amplification and reverse line blot hybridization (PCR/RLB) to detect and differentiate the pathogens causing fungal rhinosinusitis, which include five Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, and A. nidulans) and seven Mucorales species (Mucor heimalis, Mucor racemosus, Mucor cercinelloidea, Rhizopus arrhizus, Rhizopus microsporus, Rhizomucor pusillus, and Absidia corymbifera). The assay was validated with 98 well-characterized clinical isolates and 41 clinical tissue specimens. PCR/RLB showed high sensitivity and specificity, with 100% correct identifications of 98 clinical isolates and no cross-hybridization between the species-specific probes. Results for five control isolates, Candida albicans, Fusarium solani, Scedosporium apiospermum, Penicillium marneffei, and Exophiala verrucosa, were negative as judged by PCR/RLB. The analytical sensitivity of PCR/RLB was found to be 1.8 × 10(-3) ng/μl by 10-fold serial dilution of Aspergillus genomic DNA. The assay identified 35 of 41 (85.4%) clinical specimens, exhibiting a higher sensitivity than fungal culture (22 of 41; 53.7%) and direct sequencing (18 of 41; 43.9%). PCR/RLB similarly showed high specificity, with correct identification 16 of 18 specimens detected by internal transcribed spacer (ITS) sequencing and 16 of 22 detected by fungal culture, but it also has the additional advantage of being able to detect mixed infection in a single clinical specimen. The PCR/RLB assay thus provides a rapid and reliable option for laboratory diagnosis of fungal rhinosinusitis.
Topics: Aspergillus; Humans; Molecular Diagnostic Techniques; Mucorales; Mycology; Mycoses; Rhinitis; Sensitivity and Specificity; Sinusitis
PubMed: 21325541
DOI: 10.1128/JCM.02262-10 -
Applied and Environmental Microbiology Apr 2020is an industrial fungal species used for large-scale production of carotenoids. However, light-regulated physiological processes, such as carotenoid biosynthesis and...
is an industrial fungal species used for large-scale production of carotenoids. However, light-regulated physiological processes, such as carotenoid biosynthesis and phototropism, are not fully understood. In this study, we isolated and characterized three photoreceptor genes, , , and , in Bioinformatics analyses of these genes and their protein sequences revealed that the functional domains (PAS/LOV [Per-ARNT-Sim/light-oxygen-voltage] domain and zinc finger structure) of the proteins have significant homology to those of other fungal blue-light regulator proteins expressed by and The photoreceptor proteins were synthesized by heterologous expression in The chromogenic groups consisting of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) were detected to accompany BTWC-1 proteins by using high-performance liquid chromatography (HPLC) and fluorescence spectrometry, demonstrating that the proteins may be photosensitive. The absorbance changes of the purified BTWC-1 proteins seen under dark and light conditions indicated that they were light responsive and underwent a characteristic photocycle by light induction. Site-directed mutagenesis of the cysteine residual (Cys) in BTWC-1 did not affect the normal expression of the protein in but did lead to the loss of photocycle response, indicating that Cys represents a flavin-binding domain for photon detection. We then analyzed the functions of BTWC-1 proteins by complementing , , and into the counterpart knockout strains of for each gene. Transformation of the complement into knockout strains restored the positive phototropism, while the addition of complement remedied the deficiency of carotene biosynthesis in the knockout strains under conditions of illumination. These results indicate that and are involved in phototropism and light-inducible carotenogenesis. Thus, genes share a conserved flavin-binding domain and act as photoreceptors for control of different light transduction pathways in Studies have confirmed that light-regulated carotenogenesis is prevalent in filamentous fungi, especially in mucorales. However, few investigations have been done to understand photoinduced synthesis of carotenoids and related mechanisms in , a well-known industrial microbial strains. In the present study, three photoreceptor genes in were cloned, expressed, and characterized by bioinformatics and photoreception analyses, and then functional analyses of these genes were constructed in The results of this study will lead to a better understanding of photoreception and light-regulated carotenoid synthesis and other physiological responses in .
Topics: Amino Acid Sequence; Escherichia coli; Fungal Proteins; Microorganisms, Genetically-Modified; Mucorales; Photoreceptors, Microbial; Sequence Alignment
PubMed: 32033952
DOI: 10.1128/AEM.02962-19 -
Medical Mycology Apr 2019Fungi of the basal lineage order Mucorales are able to cause infections in animals and humans. Mucormycosis is a well-known, life-threatening disease especially in... (Review)
Review
Fungi of the basal lineage order Mucorales are able to cause infections in animals and humans. Mucormycosis is a well-known, life-threatening disease especially in patients with a compromised immune system. The rate of mortality and morbidity caused by mucormycosis has increased rapidly during the last decades, especially in developing countries. The systematic, phylogenetic, and epidemiological distributions of mucoralean fungi are addressed in relation to infection in immunocompromised patients. The review highlights the current achievements in (i) diagnostics and management of mucormycosis, (ii) the study of the interaction of Mucorales with cells of the innate immune system, (iii) the assessment of the virulence of Mucorales in vertebrate and invertebrate infection models, and (iv) the determination of virulence factors that are key players in the infection process, for example, high-affinity iron permease (FTR1), spore coat protein (CotH), alkaline Rhizopus protease enzyme (ARP), ADP-ribosylation factor (ARF), dihydrolipoyl dehydrogenase, calcineurin (CaN), serine and aspartate proteases (SAPs). The present mini-review attempts to increase the awareness of these difficult-to-manage fungal infections and to encourage research in the detection of ligands and receptors as potential diagnostic parameters and drug targets.
Topics: Animals; Disease Management; Disease Models, Animal; Host-Pathogen Interactions; Humans; Immunocompromised Host; Leukocytes; Mucorales; Mucormycosis; Virulence Factors
PubMed: 30816980
DOI: 10.1093/mmy/myz011 -
Clinical Microbiology and Infection :... Oct 2009Zygomycosis refers to a group of uncommon and frequently fatal mycoses caused by fungi of the class Zygomycetes, the organisms of which are usually found in decaying... (Review)
Review
Zygomycosis refers to a group of uncommon and frequently fatal mycoses caused by fungi of the class Zygomycetes, the organisms of which are usually found in decaying organic matter. Disease can be transmitted by the inhalation of spores or by direct inoculation on disrupted skin or mucosa. For rare diseases such as zygomycosis, two or more cases occurring in a short time should be investigated as a probable epidemic. Twelve hospital outbreaks and two pseudoepidemics caused by Zygomycetes have been cited in the English literature. The first epidemic was recorded in 1977 and the last in 2008. Outbreaks have been reported in the USA, the UK and elsewhere in Europe. Cases have included cutaneous, disseminated, pulmonary and rhinocerebral disease. Species identified have included Rhizopus arrhizus, Rhizopus rhizopodiformis, Rhizopus microsporus, Rhizopus spp., Absidia corymbifera and Rhizomucor pusillius. Sources of infection have included Elastoplast adhesive bandage rolls, ventilation systems, wooden tongue depressors, karaya (plant-derived adhesive) ostomy bags, and water damage to a linen store and patient shower room. Patients have included cardiosurgery patients, renal transplant recipients, orthopaedic patients, adult leukaemia patients, intensive care unit neonates, immunocompromised haematology patients, and burn unit patients. Although zygomycosis outbreaks in the hospital environment are infrequent, a high index of suspicion should exist if necrotic lesions appear in proximity to a postoperative wound. Direct tissue examination and tissue culture and histopathology must be routinely performed.
Topics: Absidia; Cross Infection; Disease Outbreaks; Europe; Hospitals; Humans; Rhizomucor; Rhizopus; United States; Zygomycosis
PubMed: 19754759
DOI: 10.1111/j.1469-0691.2009.02982.x -
Medecine Sciences : M/S Mar 2013Mucormycosis is an infection caused by filamentous fungi of the Mucorales order. The predisposing factors are mostly diabetic ketoacidosis and severe immunosuppressive... (Review)
Review
Mucormycosis is an infection caused by filamentous fungi of the Mucorales order. The predisposing factors are mostly diabetic ketoacidosis and severe immunosuppressive conditions such as prolonged neutropenia, steroid or T-cell suppressor therapy, solid organ transplantation or allogeneic hematopoietic stem cell transplantation. Mucormycosis can also occur in immunocompetent patients, especially after trauma, burns or direct inoculation of the fungi (e.g. intravenous drug abuse). The most frequently targeted primary sites of infection are sinuses with a rapid spread to the adjacent tissues including the brain, the lower respiratory tract, the digestive tract and the skin. Mucorales are able to invade the vessels causing hematogenous dissemination, vascular thrombosis and, ultimately, necrosis of the lesions. Clinical and radiological aspects are similar to those observed in other invasive filamentous fungi infections such as invasive aspergillosis, fusariosis or scedosporiosis. CT-scan or MRI are mandatory to assess the extension of the lesions. The diagnosis remains difficult and is often delayed resulting in a poor outcome.
Topics: Brain; Diabetic Ketoacidosis; Gastrointestinal Tract; Humans; Immunocompromised Host; Mucorales; Mucormycosis; Paranasal Sinuses; Radiography; Respiratory System; Skin
PubMed: 23510521
DOI: 10.1051/medsci/201329s105 -
Virulence Nov 2017Mucormycoses are life-threatening infections in immunocompromised patients. This study characterizes the response of human mononuclear cells to different Mucorales and...
Mucormycoses are life-threatening infections in immunocompromised patients. This study characterizes the response of human mononuclear cells to different Mucorales and Ascomycota. PBMC, monocytes, and monocyte derived dendritic cells (moDCs) from healthy donors were stimulated with resting and germinated stages of Mucorales and Ascomycota. Cytokine response and expression of activation markers were studied. Both inactivated germ tubes and resting spores of Rhizopus arrhizus and other human pathogenic Mucorales species significantly stimulated mRNA synthesis and secretion of proinflammatory cytokines. Moreover, R. arrhizus spores induced the upregulation of co-stimulatory molecules on moDCs and a specific T-helper cell response. Removal of rodlet hydrophobins by hydrofluoric acid treatment of A. fumigatus conidia resulted in enhanced immunogenicity, whereas the cytokine response of PBMCs to dormant R. arrhizus spores was not influenced by hydrofluoric acid. Scanning electron micrographs of Mucorales spores did not exhibit any morphological correlates of rodlet hydrophobins. Taken together, this study revealed striking differences in the response of human mononuclear cells to resting stages of Ascomycota and Mucorales, which may be explained by absence of an immunoprotective hydrophobin layer in Mucorales spores.
Topics: Cytokines; Dendritic Cells; Fungal Proteins; Humans; Leukocytes, Mononuclear; Mucorales; Mucormycosis; Phagocytes; Spores, Fungal; Th1 Cells
PubMed: 28783439
DOI: 10.1080/21505594.2017.1342920 -
Current Biology : CB Jan 2021Multicellular organisms employ fluid transport networks to overcome the limit of diffusion and promote essential long-distance transport. Connectivity and pressurization...
Multicellular organisms employ fluid transport networks to overcome the limit of diffusion and promote essential long-distance transport. Connectivity and pressurization render these networks especially vulnerable to wounding. To mitigate this risk, animals, plants, and multicellular fungi independently evolved elaborate clotting and plugging mechanisms. In the septate filamentous fungi, membrane-bound organelles plug septal pores in wounded hyphae. By contrast, vegetative hyphae in the early-diverging Mucoromycota are largely aseptate, and how their hyphae respond to wounding is unknown. Here, we show that wounding in the Mucorales leads to explosive protoplasmic discharge that is rapidly terminated by protoplasmic gelation. We identify Mucoromycota-specific Gellin proteins, whose loss of function leads to uncontrolled wound-induced protoplasmic bleeding. Gellins contain ten related β-trefoil Gll domains, each of which possesses unique features that impart distinct gelation-related properties: some readily unfold and form high-order sheet-like structures when subjected to mechanical force from flow, while others possess hydrophobic motifs that enable membrane binding. In cell-free reconstitution, sheet-like structures formed by a partial Gellin incorporate membranous organelles. Together, these data define a mechanistic basis for regulated protoplasmic gelation, and provide new design principles for the development of artificial flow-responsive biomaterials.
Topics: Cytoplasm; Fungal Proteins; Hydrodynamics; Hyphae; Intravital Microscopy; Loss of Function Mutation; Mucor; Protein Domains; Protein Multimerization
PubMed: 33186551
DOI: 10.1016/j.cub.2020.10.016