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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 -
Frontiers in Cellular and Infection... 2022Recently, India witnessed an unprecedented surge of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) cases. In addition to patient management issues,...
INTRODUCTION
Recently, India witnessed an unprecedented surge of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) cases. In addition to patient management issues, environmental Mucorales contamination possibly contributed to the outbreak. A recent study evaluated environment contamination by Mucorales in the hospital setting. However, a considerable number of CAM patients were never admitted to a hospital before the development of the disease. The present study, therefore, planned to evaluate Mucorales contamination of patients' residences.
METHODS
The residential environment of 25 patients with CAM living in north India was surveyed. Air samples were collected from indoor and immediate outdoor vicinity of the patients' residence and cultured on Dichloran Rose-Bengal Chloramphenicol (DRBC) agar with benomyl for selective isolation of Mucorales. Surface swab samples were also collected from the air coolers fitted in those residences and cultured on DRBC agar. The isolates were identified by phenotypic and genotypic methods. Amplified fragment length polymorphism (AFLP) was employed to evaluate the genetic relatedness of the environmental and patients' clinical isolates.
RESULTS
The median spore count (mean ± SD, cfu/m) of Mucorales in the air of patients' bedrooms was significantly higher than in the air in other rooms in those residences (3.55 versus 1.5, p = 0.003) or the air collected directly from the front of the air cooler (p < 0.0001). The Mucorales spore count in the environment did not correlate with either ventilation of the room or hygiene level of the patients' residences. was isolated from the environment of all patients' residences (n = 25); other Mucorales species isolated were (n = 14), (n = 6), (n = 6), (n = 1), (n = 1), and (n = 1). Genetic relatedness was observed between 11 environmental isolates from the patients' bedrooms and respective clinical isolates from patients.
DISCUSSION
The study supported the view that the patients might have acquired Mucorales from the home environment during the post-COVID-19 convalescence period. Universal masking at home during patients' convalescence period and environmental decontamination could minimize exposure in those susceptible patients.
Topics: Agar; Amplified Fragment Length Polymorphism Analysis; Benomyl; COVID-19; Chloramphenicol; Convalescence; Humans; Mucorales; Mucormycosis
PubMed: 36118044
DOI: 10.3389/fcimb.2022.953750 -
International Journal of... 2023Mucormycosis is called as black fungus, which is caused by fungus belonged to Mucorales. If this fungus, effects healthy individuals it won't cause any serious...
Mucormycosis is called as black fungus, which is caused by fungus belonged to Mucorales. If this fungus, effects healthy individuals it won't cause any serious complications, but it may cause life-threatening issues when Mucorales affects individuals who have low immunity. The mortality rate of black fungus is more than 50%, and it may also range till 100% if the individual is having any preexisting or chronic disease. This was the case of a 55-year-old male patient complaint of having generalized pain in the maxillary teeth bilaterally and suffering fullness in the maxillary sinus. To check on other possible diseases, doctors have conducted other diagnosis tests, and orthopantomogram revealed in the diagnosis that there was the presence of haziness in the left maxillary sinus, which looked like an incompletely formed soap bubble and additionally he diagnosed with coronavirus disease positive. Then, doctors suggested a chest computerized tomography (CT) along with head CT excluding the brain and further investigation of this case was given below in detail. The report reveals acute necrotizing suppurative sinusitis with dead bony tissue, soft-tissue necrosis with fungal infestation showing broad hyphae with right-angle branching suggestive of mucormycosis.
Topics: Male; Humans; Middle Aged; Mucormycosis; Coronavirus; Mucorales; Sinusitis
PubMed: 36926770
DOI: 10.4103/ijmy.ijmy_207_22 -
Natural Product Reports Oct 2018A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as... (Review)
Review
A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as huperphlegmine A from Huperzia phlegmaria.
Topics: Alkaloids; Biochemistry; Biological Products; Fatty Acids, Unsaturated; Genome, Bacterial; Huperzia; Molecular Structure; Mucor; Pseudomonas; Strobilurins; Sulfoxides
PubMed: 30209473
DOI: 10.1039/c8np90032a -
Journal de Mycologie Medicale Aug 2022
Topics: COVID-19; Humans; India; Mucorales; Mucormycosis
PubMed: 35364402
DOI: 10.1016/j.mycmed.2022.101275 -
International Journal of Infectious... Aug 2021Mucormycosis is a rare invasive fungal infection with high mortality in patients with severe underlying predisposing factors causing immunosuppression. The exact...
INTRODUCTION
Mucormycosis is a rare invasive fungal infection with high mortality in patients with severe underlying predisposing factors causing immunosuppression. The exact incidence of mucormycosis and the optimal therapeutic approach is difficult to determine, especially in severe cases, due to the rarity of the disease. The new second-generation triazole isavuconazole provides an alternative treatment option which may represent a potential benefit in severe cases.
MATERIALS AND METHODS
A retrospective case series was conducted of patients with a positive laboratory culture for Mucorales and consistent clinical findings who required intensive care treatment. Patient characteristics including demographics, comorbidities, microbiological analysis, specific antifungal therapy and clinical outcome were analysed.
RESULTS
Fifteen critically ill patients with Mucorales detected between 2016 and 2019 were included in this study; the crude mortality rate was 100%. At the time of diagnosis of mucormycosis, 80% of subjects had relevant medical immunosuppression and 53.3% of subjects had neutropenia. Manifestation of mucormycosis was pulmonary in 53.3% of subjects, rhino-orbital in 20% of subjects and disseminated in 26.7% of subjects. Notably, 40% of all patients had received antifungal prophylaxis prior to mucormycosis, mainly with posaconazole due to underlying haematological malignancy, thus possibly representing break-through infections. Antifungal therapy for invasive mucormycosis was administered in 80% of subjects for a median duration of 16 days.
CONCLUSION
In this retrospective cohort analysis of intensive care patients, the prognosis of mucormycosis was extremely poor. An aggressive strategy for diagnosis and treatment is essential for intensive care patients with mucormycosis. There is a need for further research to determine if combination therapy in higher dosages or prompt surgery is beneficial in severe critically ill patients.
Topics: Antifungal Agents; Critical Illness; Humans; Mucorales; Mucormycosis; Retrospective Studies
PubMed: 34229089
DOI: 10.1016/j.ijid.2021.06.066 -
MBio Aug 2018Mucormycosis is a life-threatening, invasive fungal infection that is caused by various species belonging to the order Mucorales. species are the most common cause of...
Mucormycosis is a life-threatening, invasive fungal infection that is caused by various species belonging to the order Mucorales. species are the most common cause of the disease, responsible for approximately 70% of all cases of mucormycosis. During pulmonary mucormycosis, inhaled spores must adhere to and invade airway epithelial cells in order to establish infection. The molecular mechanisms that govern this interaction are poorly understood. We performed an unbiased survey of the host transcriptional response during early stages of var. () infection in a murine model of pulmonary mucormycosis using transcriptome sequencing (RNA-seq). Network analysis revealed activation of the host's epidermal growth factor receptor (EGFR) signaling. Consistent with the RNA-seq results, EGFR became phosphorylated upon infection of human alveolar epithelial cells with several members of the Mucorales, and this phosphorylated, activated form of EGFR colocalized with spores. Inhibition of EGFR signaling with cetuximab or gefitinib, specific FDA-approved inhibitors of EGFR, significantly reduced the ability of to invade and damage airway epithelial cells. Furthermore, gefitinib treatment significantly prolonged survival of mice with pulmonary mucormycosis, reduced tissue fungal burden, and attenuated the activation of EGFR in response to pulmonary mucormycosis. These results indicate EGFR represents a novel host target to block invasion of alveolar epithelial cells by , and inhibition of EGFR signaling provides a novel approach for treating mucormycosis by repurposing an FDA-approved drug. Mucormycosis is an increasingly common, highly lethal fungal infection with very limited treatment options. Using a combination of animal models, transcriptomics, cell biology, and pharmacological approaches, we have demonstrated that Mucorales fungi activate EGFR signaling to induce fungal uptake into airway epithelial cells. Inhibition of EGFR signaling with existing FDA-approved drugs significantly increased survival following var. infection in mice. This study enhances our understanding of how Mucorales fungi invade host cells during the establishment of pulmonary mucormycosis and provides a proof-of-concept for the repurposing of FDA-approved drugs that target EGFR function.
Topics: A549 Cells; Animals; Cetuximab; Disease Models, Animal; ErbB Receptors; Gefitinib; Gene Regulatory Networks; Host-Pathogen Interactions; Humans; Lung; Male; Mice; Mice, Inbred ICR; Mucormycosis; Phosphorylation; Protein Kinase Inhibitors; Rhizopus; Sequence Analysis, RNA; Signal Transduction
PubMed: 30108171
DOI: 10.1128/mBio.01384-18 -
International Ophthalmology Jun 2023Mucormycosis is a severe fungal infection caused by species of the order Mucorales. Early and accurate diagnosis is a prerequisite in the management of the disease. In...
PURPOSE
Mucormycosis is a severe fungal infection caused by species of the order Mucorales. Early and accurate diagnosis is a prerequisite in the management of the disease. In the present study, we evaluated and compared two PCR-based techniques for the diagnosis and identification of mucormycosis in patients with rhino-orbital mucormycosis (ROM) post-COVID-19.
METHODS
Diagnosed clinically and radiologically, 25 patients of ROM were included in the study and endoscopically or blind collected nasal swabs or orbital tissues were submitted for microbiological evaluation (direct microscopy + culture) and PCR using primers targeting two different loci (ITS and 28S rDNA region) for diagnosis. All PCR products were further processed for species identification using Sanger sequencing whenever possible.
RESULT
Of the 25 samples included in the study, 16 samples were positive for presence of fungal filaments by Smear suggestive of Mucorales sp., but only 7/25 grew in culture. ITS-based PCR was able to identify mucormycosis in 7/25 (28%) samples and 28S rDNA PCR showed positivity for 19/25 (76%) samples. Rhizopus oryzae was found to be the predominant species in our study. The sensitivity and specificity of 28S rDNA PCR compared to culture were found to be 85.71% and 27.78%, respectively, while for ITS-based PCR, they were 42.86% and 77.78%, respectively.
CONCLUSIONS
28S rDNA-based PCR is a reliable and sensitive method for early diagnosis of mucormycosis. Molecular techniques have shown a promising future to provide quick and effective treatment by accurately identifying the aetiologic agent.
Topics: Humans; Mucormycosis; COVID-19; Mucorales; Mycoses; DNA, Ribosomal; Eye Diseases; COVID-19 Testing
PubMed: 36414852
DOI: 10.1007/s10792-022-02577-y -
Journal of Clinical Microbiology Aug 2021The global incidence of mucormycosis has increased in recent years owing to higher numbers of individuals at risk for these infections. The diagnosis and treatment of...
The global incidence of mucormycosis has increased in recent years owing to higher numbers of individuals at risk for these infections. The diagnosis and treatment of this aggressive fungal infection are of clinical concern due to differences in species distribution in different geographic areas and susceptibility profiles between different species that are capable of causing highly aggressive infections. The purpose of this study was to evaluate the epidemiology and susceptibility profiles of Mucorales isolates in the United States over a 52-month period. Species identification was performed by combined phenotypic characteristics and DNA sequence analysis, and antifungal susceptibility testing was performed by CLSI M38 broth microdilution for amphotericin B, isavuconazole, itraconazole, and posaconazole. During this time frame, 854 isolates were included, representing 11 different genera and over 26 species, of which (58.6%) was the predominant genus, followed by (19.6%). The majority of isolates were cultured from the upper and lower respiratory tracts (55%). Amphotericin B demonstrated the most potent activity, with geometric mean (GM) MICs of ≤0.25 μg/ml against all genera with the exception of species (GM MIC of 1.30 μg/ml). In head-to-head comparisons, the most active azole was posaconazole, followed by isavuconazole. Differences in azole and amphotericin B susceptibility patterns were observed between the genera with the greatest variability observed with isavuconazole. Awareness of the epidemiology of Mucorales isolates and differences in antifungal susceptibility patterns in the United States may aide clinicians in choosing antifungal treatment regimens. Further studies are warranted to correlate these findings with clinical outcomes.
Topics: Amphotericin B; Antifungal Agents; Fungi; Humans; Itraconazole; Microbial Sensitivity Tests; Mucorales; Mucormycosis; United States
PubMed: 34232068
DOI: 10.1128/JCM.01230-21 -
Pathology, Research and Practice Aug 2022Due to Corona Virus disease -19, India saw a surge of mucormycosis cases, associated with high death rate. India, during the month of May to July 2021 saw a surge of...
INTRODUCTION
Due to Corona Virus disease -19, India saw a surge of mucormycosis cases, associated with high death rate. India, during the month of May to July 2021 saw a surge of mucormycosis from all states, with close to 50,000 cases just in a span of 3 months.
OBJECTIVE
To examine the histopathological appearances of rhino-orbital/rhino-maxillary/sino-nasal mucormycosis in the backdrop of the ongoing COVID 19 pandemic.
MATERIAL AND METHODS
The study involved analysis of 60 biopsy samples of suspected rhino-maxillary /rhino-orbital mucormycosis received from post-COVID-19 patients. A preliminary review of the slides showing hyphal forms of fungal organisms with un-doubtful tissue / mucosal invasion was included. All samples were examined under Hematoxylin and Eosin stains along with special fungal stains. Data thus obtained were analyzed statistically. Special stains for fungus namely Periodic Acidic Schiff (PAS) and Gomori Methenamine silver (GMS) were utilized to confirm and/or to differentiate the fungal organisms and to highlight the cell wall of the fungus.
RESULTS
The mean age of the patients with mucormycosis was 51.68 years and 72 (83.33%) of them were males. Acute type of inflammation was noted in 44 (73.33%), granulomatous inflammation in 14 (23.33%) of cases. Bony invasion and perineural invasion was observed in 5 (8.33%) and 55 (91.67%) cases, respectively. The dominant fungus were mucorales in 58 (96.67%), aspergillous, along with mucorales in 12 (20%) and combination of mucorales and candida identified in 8 (13.33%) cases.
CONCLUSION
Besides all the histological appearance of angioinvasion, bone, and soft tissue invasion, a notable aspect was the shift in inflammatory pattern, which was more granulomatous in nature, with a decrease in fungal load correlating with the drop of COVID second wave. This proves that as immunity develops, the host's response to secondary opportunistic infections changes.
Topics: COVID-19; Female; Humans; Male; Middle Aged; Mucorales; Mucormycosis; Pandemics; Retrospective Studies
PubMed: 35749915
DOI: 10.1016/j.prp.2022.153981