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Expert Review of Respiratory Medicine Jul 2020Fungal infections are increasingly encountered in clinical practice due to more favorable environmental conditions and increasing prevalence of immunocompromised... (Review)
Review
INTRODUCTION
Fungal infections are increasingly encountered in clinical practice due to more favorable environmental conditions and increasing prevalence of immunocompromised individuals. The diagnostic approach for many fungal pathogens continues to evolve. Herein, we outline available diagnostic tests for the most common fungal infections with a focus on recent advances and future directions.
AREAS COVERED
We discuss the diagnostic testing methods for angioinvasive molds ( spp. and spp.), invasive yeast ( spp. and ssp.), Pneumocystis, and endemic fungi ( sp., Coccidioides sp., and Hitoplasma sp.). The PubMed-NCBI database was searched within the past 5 years to identify the most recent available literature with dates extended in cases where literature was sparse. Diagnostic guidelines were utilized when available with references reviewed.
EXPERT OPINION
Historically, culture and/or direct visualization of fungal organisms were required for diagnosis of infection. Significant limitations included ability to collect specimens and delayed diagnosis associated with waiting for culture results. Antigen and antibody testing have made great strides in allowing quicker diagnosis of fungal infections but can be limited by low sensitivity/specificity, cross-reactivity with other fungi, and test availability. Molecular methods have a rich history in some fungal diseases, while others continue to be developed.
Topics: Aspergillus; Blastomyces; Candida; Coccidioides; Cryptococcus; Histoplasma; Humans; Lung Diseases, Fungal; Mucor; Pneumocystis; Pneumonia
PubMed: 32290725
DOI: 10.1080/17476348.2020.1753506 -
The Journal of Antimicrobial... Mar 2017Infections caused by filamentous fungi represent a major burden in the ICU. Invasive aspergillosis is emerging in non-neutropenic individuals with predisposing... (Review)
Review
Infections caused by filamentous fungi represent a major burden in the ICU. Invasive aspergillosis is emerging in non-neutropenic individuals with predisposing conditions, e.g. corticosteroid treatment, chronic obstructive pulmonary disease, liver cirrhosis, solid organ cancer, HIV infection and transplantation. Diagnosis is challenging because the signs and symptoms are non-specific, and initiation of additional diagnostic examinations is often delayed because clinical suspicion is low. Isolation of an Aspergillus species from the respiratory tract in critically ill patients, and tests such as serum galactomannan, bronchoalveolar lavage 1-3-β-d-glucan and specific PCR should be interpreted with caution. ICU patients should start adequate antifungal therapy upon suspicion of invasive aspergillosis, without awaiting definitive proof. Voriconazole, and now isavuconazole, are the drugs of choice. Mucormycosis is a rare, but increasingly prevalent disease that occurs mainly in patients with uncontrolled diabetes mellitus, immunocompromised individuals or previously healthy patients with open wounds contaminated with Mucorales. A high proportion of cases are diagnosed in the ICU. Rapidly progressing necrotizing lesions in the rhino-sinusal area, the lungs or skin and soft tissues are the characteristic presentation. Confirmation of diagnosis is based on demonstration of tissue invasion by non-septate hyphae, and by new promising molecular techniques. Control of underlying predisposing conditions, rapid surgical resection and administration of liposomal amphotericin B are the main therapeutic actions, but new agents such as isavuconazole are a promising alternative. Patients with mucormycosis receive a substantial part of their care in ICUs and, despite advances in diagnosis and treatment, mortality remains very high.
Topics: Antifungal Agents; Aspergillosis; Aspergillus; Critical Illness; Galactose; Humans; Immunocompromised Host; Intensive Care Units; Invasive Fungal Infections; Lung Diseases, Fungal; Mannans; Mucor; Mucormycosis; Nitriles; Opportunistic Infections; Pyridines; Respiratory System; Triazoles; Voriconazole; beta-Glucans
PubMed: 28355466
DOI: 10.1093/jac/dkx032 -
Microbiological Reviews Jun 1991Mucor dimorphism has interested microbiologists since the time of Pasteur. When deprived of oxygen, these fungi grow as spherical, multipolar budding yeasts. In the... (Review)
Review
Mucor dimorphism has interested microbiologists since the time of Pasteur. When deprived of oxygen, these fungi grow as spherical, multipolar budding yeasts. In the presence of oxygen, they propagate as branching coenocytic hyphae. The ease with which these morphologies can be manipulated in the laboratory, the diverse array of morphopoietic agents available, and the alternative developmental fates that can be elicited from a single cell type (the sporangiospore) make Mucor spp. a highly propitious system in which to study eukaryotic cellular morphogenesis. The composition and organization of the cell wall differ greatly in Mucor yeasts and hyphae. The deposition of new wall polymers is isodiametric in yeasts and apically polarized in hyphae. Current research has focused on the identity and control of enzymes participating in wall synthesis. An understanding of how the chitosome interacts with appropriate effectors, specific enzymes, and the plasma membrane to assemble chitin-chitosan microfibrils and to deposit them at the proper sites on the cell exterior will be critical to elucidating dimorphism. Several biochemical and physiological parameters have been reported to fluctuate in a manner that correlates with Mucor morphogenesis. The literature describing these has been reviewed critically with the intent of distinguishing between causal and casual connections. The advancement of molecular genetics has afforded powerful new tools that researchers have begun to exploit in the study of Mucor dimorphism. Several genes, some encoding products known to correlate with development in Mucor spp. or other fungi, have been cloned, sequenced, and examined for transcriptional activity during morphogenesis. Most have appeared in multiple copies displaying independent transcriptional control. Selective translation of stored mRNA molecules occurs during sporangiospore germination. Many other correlates of Mucor morphogenesis, presently described but not yet explained, should prove amenable to analysis by the emerging molecular technology.
Topics: Carbon; Cell Wall; Energy Metabolism; Fungal Proteins; Genes, Fungal; Morphogenesis; Mucor; Nitrogen; Second Messenger Systems
PubMed: 1886520
DOI: 10.1128/mr.55.2.234-258.1991 -
Bioinformatics (Oxford, England) May 2016There are many tools for variant calling and effect prediction, but little to tie together large sample groups. Aggregating, sorting and summarizing variants and effects...
MOTIVATION
There are many tools for variant calling and effect prediction, but little to tie together large sample groups. Aggregating, sorting and summarizing variants and effects across a cohort is often done with ad hoc scripts that must be re-written for every new project. In response, we have written MuCor, a tool to gather variants from a variety of input formats (including multiple files per sample), perform database lookups and frequency calculations, and write many types of reports. In addition to use in large studies with numerous samples, MuCor can also be employed to directly compare variant calls from the same sample across two or more platforms, parameters or pipelines. A companion utility, DepthGauge, measures coverage at regions of interest to increase confidence in calls.
AVAILABILITY AND IMPLEMENTATION
Source code is freely available at https://github.com/blachlylab/mucor and a Docker image is available at https://hub.docker.com/r/blachlylab/mucor/
CONTACT
[email protected] data: Supplementary data are available at Bioinformatics online.
Topics: Algorithms; Animals; Computational Biology; Humans; Mutation; Programming Languages; Sample Size; Software
PubMed: 26803155
DOI: 10.1093/bioinformatics/btw028 -
Frontiers in Veterinary Science 2022A retrospective study was conducted on parrots submitted from necropsy to the Department of Veterinary Pathology, School of Biosciences and Veterinary, University of...
A retrospective study was conducted on parrots submitted from necropsy to the Department of Veterinary Pathology, School of Biosciences and Veterinary, University of Camerino, Italy, from 2007 to 2018. From a total of 2,153 parrots examined at post-mortem, four cases were diagnosed with atypical mycosis and were considered for determination of the fungus species by PCR. A Fischer's lovebird (), Peach-faced lovebirds (), and two Blue and Gold Macaws () from four different aviaries died after some days of lethargy and ruffled feathers. Records of gross necropsy and histopathological exams (H&E, PAS, and Grocott stain) were described and biomolecular analyses were carried out. No specific gross lesions were appreciated at necropsy, while histopathology evidenced a systemic mycosis in several organs, particularly in the lungs. In affected organs, broad and non-septate hyphae, suggestive of mycoses, were observed. Molecularly, (Fischer's lovebird) and (Peach-faced lovebirds) were identified from formalin-fixed and paraffin-embedded (FFPE) lung and liver tissue. In addition, and spp. (respectively in male and female Blue and Gold macaws) were identified in FFPE tissue from several organs; whereas the role of spp. as true pathogens is well-demonstrated, and the behavior of and spp. in macaws as opportunistic pathogens have been discussed. To our knowledge, this report is the first one reporting mucormycosis caused by and in lovebirds, and and spp. in macaws.
PubMed: 35647088
DOI: 10.3389/fvets.2022.883276 -
MBio Feb 2023Mucormycosis is an invasive fungal infection caused by certain members of the fungal order of Mucorales. The species most frequently identified as the etiological agents...
Mucormycosis is an invasive fungal infection caused by certain members of the fungal order of Mucorales. The species most frequently identified as the etiological agents of mucormycosis belong to the genera , , and . The frequency of systemic mucormycosis has been increasing, mainly because of increasing numbers of susceptible patients. Furthermore, Mucorales display intrinsic resistance to the majority of routinely used antifungal agents (e.g., echinocandins and short-tailed azoles), which limits the number of possible therapeutic options. All the above-mentioned issues urge the improvement of molecular identification methods and the discovery of new antifungal targets and strategies. Spore coat proteins (CotH) constitute a kinase family present in many pathogenic bacteria and fungi and participate in the spore formation in these organisms. Moreover, some of them can act as virulence factors being receptors of the human GRP78 protein during Rhizopus delemar-induced mucormycosis. We identified 17 -like genes in the Mucor lusitanicus genome database. Successful disruption of five genes in was performed using the CRISPR-Cas9 system. The CotH3 and CotH4 proteins play a role in adaptation to different temperatures as well as in developing the cell wall structure. We also show CotH4 protein is involved in spore wall formation by affecting the total chitin content and, thus, the composition of the spore wall. The role of CotH3 and CotH4 proteins in virulence was confirmed in two invertebrate models and a diabetic ketoacidosis (DKA) mouse model. Current treatment options for mucormycosis are inadequate, resulting in high mortality rates, especially among immunosuppressed patients. The development of novel therapies for mucormycosis has been hampered by lack of understanding of the pathogenetic mechanisms. The importance of the cell surface CotH proteins in the pathogenesis of -mediated mucormycosis has been recently described. However, the contribution of this family of proteins to the virulence of other mucoralean fungi and their functionality in vital processes remain undefined. Through the use of the CRISPR-Case9 gene disruption system, we demonstrate the importance of several of the CotH proteins to the virulence of Mucor lusitanicus by using three infection models. We also report on the importance of one of these proteins, CotH4, to spore wall formation by affecting chitin content. Therefore, our studies extend the importance of CotH proteins to and identify the mechanism by which one of the CotH proteins contributes to the development of a normal fungal cell wall, thereby indicating that this family of proteins can be targeted for future development of novel therapeutic strategies of mucormycosis.
Topics: Animals; Mice; Humans; Mucor; Mucormycosis; Virulence; Mucorales; Spores
PubMed: 36625576
DOI: 10.1128/mbio.03386-22 -
Clinical Microbiology Reviews Apr 2011Rhizopus, Mucor, and Lichtheimia (formerly Absidia) species are the most common members of the order Mucorales that cause mucormycosis, accounting for 70 to 80% of all... (Review)
Review
Rhizopus, Mucor, and Lichtheimia (formerly Absidia) species are the most common members of the order Mucorales that cause mucormycosis, accounting for 70 to 80% of all cases. In contrast, Cunninghamella, Apophysomyces, Saksenaea, Rhizomucor, Cokeromyces, Actinomucor, and Syncephalastrum species individually are responsible for fewer than 1 to 5% of reported cases of mucormycosis. In this review, we provide an overview of the epidemiology, clinical manifestations, diagnosis of, treatment of, and prognosis for unusual Mucormycetes infections (non-Rhizopus, -Mucor, and -Lichtheimia species). The infections caused by these less frequent members of the order Mucorales frequently differ in their epidemiology, geographic distribution, and disease manifestations. Cunninghamella bertholletiae and Rhizomucor pusillus affect primarily immunocompromised hosts, mostly resulting from spore inhalation, causing pulmonary and disseminated infections with high mortality rates. R. pusillus infections are nosocomial or health care related in a large proportion of cases. While Apophysomyces elegans and Saksenaea vasiformis are occasionally responsible for infections in immunocompromised individuals, most cases are encountered in immunocompetent individuals as a result of trauma, leading to soft tissue infections with relatively low mortality rates. Increased knowledge of the epidemiology and clinical presentations of these unusual Mucormycetes infections may improve early diagnosis and treatment.
Topics: Antifungal Agents; Fungi; Humans; Mucormycosis; Prognosis; Treatment Outcome
PubMed: 21482731
DOI: 10.1128/CMR.00056-10 -
Environmental Science and Pollution... Oct 2022The emergence of various diseases during the COVID-19 pandemic made health workers more attentive, and one of the new pathogens is the black fungus (mucormycosis). As a... (Review)
Review
The emergence of various diseases during the COVID-19 pandemic made health workers more attentive, and one of the new pathogens is the black fungus (mucormycosis). As a result, millions of lives have already been lost. As a result of the mutation, the virus is constantly changing its traits, including the rate of disease transmission, virulence, pathogenesis, and clinical signs. A recent analysis revealed that some COVID-19 patients were also coinfected with a fungal disease called mucormycosis (black fungus). India has already categorized the COVID-19 patient black fungus outbreak as an epidemic. Only a few reports are observed in other countries. The immune system is weakened by COVID-19 medication, rendering it more prone to illnesses like black fungus (mucormycosis). COVID-19, which is caused by a B.1.617 strain of the SARS-CoV-2 virus, has been circulating in India since April 2021. Mucormycosis is a rare fungal infection induced by exposure to a fungus called mucormycete. The most typically implicated genera are Mucor rhyzuprhizopusdia and Cunninghamella. Mucormycosis is also known as zygomycosis. The main causes of infection are soil, dumping sites, ancient building walls, and other sources of infection (reservoir words "mucormycosis" and "zygomycosis" are occasionally interchanged). Zygomycota, on the other hand, has been identified as polyphyletic and is not currently included in fungal classification systems; also, zygomycosis includes Entomophthorales, but mucormycosis does not. This current review will be focused on the etiology and virulence factors of COVID-19/mucormycosis coinfections in COVID-19-associated mucormycosis patients, as well as their prevalence, diagnosis, and treatment.
Topics: COVID-19; Humans; Mucor; Mucormycosis; Pandemics; SARS-CoV-2; Soil; Virulence Factors
PubMed: 35986111
DOI: 10.1007/s11356-022-22204-8 -
Applied Microbiology and Biotechnology Aug 2021Regulation of signal transduction pathways is crucial for the maintenance of cellular homeostasis and organismal development in fungi. Transcription factors are key... (Review)
Review
Regulation of signal transduction pathways is crucial for the maintenance of cellular homeostasis and organismal development in fungi. Transcription factors are key elements of this regulatory network. The basic-region leucine zipper (bZIP) domain of the bZIP-type transcription factors is responsible for DNA binding while their leucine zipper structural motifs are suitable for dimerization with each other facilitiating the formation of homodimeric or heterodimeric bZIP proteins. This review highlights recent knowledge on the function of fungal orthologs of the Schizosaccharomyces pombe Atf1, Aspergillus nidulans AtfA, and Fusarium verticillioides FvAtfA, bZIP-type transcription factors with a special focus on pathogenic species. We demonstrate that fungal Atf1-AtfA-FvAtfA orthologs play an important role in vegetative growth, sexual and asexual development, stress response, secondary metabolite production, and virulence both in human pathogens, including Aspergillus fumigatus, Mucor circinelloides, Penicillium marneffei, and Cryptococcus neoformans and plant pathogens, like Fusarium ssp., Magnaporthe oryzae, Claviceps purpurea, Botrytis cinerea, and Verticillium dahliae. KEY POINTS: • Atf1 orthologs play crucial role in the growth and development of fungi. • Atf1 orthologs orchestrate environmental stress response of fungi. • Secondary metabolite production and virulence are coordinated by Atf1 orthologs.
Topics: Ascomycota; Aspergillus nidulans; Botrytis; Fungal Proteins; Fusarium; Humans; Mucor; Talaromyces
PubMed: 34302199
DOI: 10.1007/s00253-021-11431-7 -
Indian Journal of Ophthalmology Jun 2021
Topics: COVID-19; Humans; Mucor; Mucormycosis; Orbital Diseases; SARS-CoV-2
PubMed: 34011699
DOI: 10.4103/ijo.IJO_1165_21