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1.
BMC Infect Dis ; 24(1): 852, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39174954

ABSTRACT

BACKGROUND: To evaluate the demographic, clinical, and prognostic characteristics of patients diagnosed with COVID-19-associated mucormycosis (CAM) in Iranian patients. METHODS: This prospective observational study was conducted in 8 tertiary referral ophthalmology centers in different provinces of Iran during the fifth wave of the COVID-19 pandemic. All patients were subjected to complete history taking and comprehensive ophthalmological examination and underwent standard accepted treatment strategy based on the disease stage. RESULTS: Two hundred seventy-four CAM patients (most were males (150, 54.7%)) with a mean age of 56.8 ± 12.44 years were enrolled. Patients with a history of cigarette smoking (Adjusted Odds Ratio (AOR) = 4.36), Intensive Care Unit admission (ICU) (AOR = 16.26), higher stage of CAM (AOR = 2.72), and receiving endoscopic debridement and transcutaneous retrobulbar amphotericin B (AOR = 3.30) had higher odds of mortality. History of taking systemic corticosteroids during COVID-19 was significantly associated with reduced odds of mortality (AOR = 0.16). Generalized Estimating Equations analysis showed that the visual acuity of deceased patients (LogMAR: 3.71, 95% CI: 3.04-4.38) was worse than that of patients who were discharged from the hospital (LogMAR: 2.42, 95% CI: 2.16-2.68) (P < 0.001). CONCLUSIONS: This study highlights significant risk factors for mortality in patients with CAM, such as cigarette smoking, ICU admission, advanced CAM stages, receiving transcutaneous retrobulbar amphotericin B and worser visual acuity. Conversely, a history of systemic corticosteroid use during COVID-19 was linked to reduced mortality. These findings underscore the critical need for early identification and targeted interventions for high-risk CAM patients to improve clinical outcomes.


Subject(s)
COVID-19 , Mucormycosis , SARS-CoV-2 , Humans , COVID-19/complications , COVID-19/mortality , COVID-19/epidemiology , Male , Middle Aged , Iran/epidemiology , Female , Risk Factors , Mucormycosis/epidemiology , Mucormycosis/mortality , Mucormycosis/drug therapy , Mucormycosis/complications , Prospective Studies , Aged , Adult , Antifungal Agents/therapeutic use , Intensive Care Units/statistics & numerical data , Amphotericin B/therapeutic use , Debridement
2.
Biomedica ; 44(2): 135-143, 2024 05 30.
Article in English, Spanish | MEDLINE | ID: mdl-39088531

ABSTRACT

Mucormycosis is a rare fungal infection caused by fungi of the Mucorales order that occurs in immunocompromised individuals or with loss of skin or mucosa barrier integrity. This report presents four cases of rhinocerebral mucormycosis attended at a third-level hospital in Cali (Colombia) during a period of three years. All patients had different case histories and times of evolution. All four had a previous or de novo diagnosis of type 2 diabetes mellitus, with glycated hemoglobin higher than 10% on admission. We ruled out other possible pathologies that could explain their immunocompromised condition. Mucormycosis diagnosis was made with direct visualization of hyaline coenocytic hyphae on biopsies. The basis of treatment was liposomal amphotericin B and surgical debridement. Two patients presented bacterial coinfection. One asked for voluntary discharge without having completed the treatment, and another one died. The remaining two have attended controls and had an adequate evolution.


La mucormicosis es una infección fúngica poco frecuente causada por hongos del orden Mucorales, la cual se presenta en individuos inmunocomprometidos o con pérdida de la integridad de la barrera de piel o mucosas. Se reportan cuatro casos de mucormicosis rinocerebral atendidos en un hospital de tercer nivel de Cali (Colombia) durante un periodo de tres años. Los cuatro pacientes presentaron diferentes cuadros clínicos y tiempos de evolución. Todos tenían diagnóstico de diabetes mellitus de tipo 2, de novo o previo, con una hemoglobina glucosilada de ingreso mayor del 10 % y en todos se descartaron otras enfermedades que explicaran su compromiso inmunitario. La mucormicosis se diagnosticó por la visualización directa de hifas hialinas sincitiales (coenocytic) en las biopsias tomadas. El pilar del tratamiento fue la anfotericina B liposómica junto con el desbridamiento quirúrgico. Dos pacientes presentaron coinfección bacteriana. De los cuatro, uno firmó su egreso voluntario sin completar el tratamiento y otro falleció. Los dos pacientes restantes han asistido a los controles y han mostrado una adecuada evolución.


Subject(s)
Amphotericin B , Mucormycosis , Humans , Mucormycosis/diagnosis , Male , Middle Aged , Amphotericin B/therapeutic use , Female , Antifungal Agents/therapeutic use , Diabetes Mellitus, Type 2/complications , Aged , Debridement , Immunocompromised Host
3.
Indian J Tuberc ; 71(3): 366-369, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39111949

ABSTRACT

BACKGROUND: Pulmonary Mucormycosis (PM) is a relatively uncommon fungal disease, usually manifested in immunocompromised patients. It has an aggressive course, along with dilemmas in diagnosis and treatment. In view of the surge of Mucormycosis patients in COVID 19 pandemic, clinicians need to consider PM in suspected cases, and act in an expedited manner to avoid misdiagnosis and initiate prompt treatment. CASE PRESENTATION: In this case series, we present four cases of PM with varied presentation, clinical course and discuss management strategies. CONCLUSIONS: A strong suspicion of PM based on epidemiological and clinical findings should be considered, to ensure appropriate and timely treatment. It should be accompanied by judicious use of corticosteroids and aggressive control of comorbid conditions to decrease preventable morbidity and mortality.


Subject(s)
COVID-19 , Lung Diseases, Fungal , Mucormycosis , Humans , Mucormycosis/diagnosis , COVID-19/complications , COVID-19/diagnosis , Male , Middle Aged , Female , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/drug therapy , Adult , Antifungal Agents/therapeutic use , SARS-CoV-2 , Tomography, X-Ray Computed
4.
BMJ Case Rep ; 17(8)2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39122378

ABSTRACT

Pulmonary mucormycosis is a rare, life-threatening fungal infection usually seen in immunocompromised patients. Mortality in such patients is high due to underlying immunosuppression and poor general condition of the patients. Invasion of the adjacent structures is known but, to the best of our knowledge, pulmonary mucormycosis presenting with a full thickness chest wall erosion has not been reported. We report such a case with chest wall destruction with superadded bacterial infection. The use of prosthetic materials for chest wall reconstruction was not possible due to the presence of infection. In addition, there were other intra-operative and post-operative challenges which we managed using a multidisciplinary approach. This report highlights the successful outcome of this complex situation using pre-operative optimisation, adequate surgical debridement and effective management of post-operative complications with patience and perseverance.


Subject(s)
Antifungal Agents , Debridement , Lung Diseases, Fungal , Mucormycosis , Thoracic Wall , Humans , Mucormycosis/diagnosis , Mucormycosis/surgery , Mucormycosis/therapy , Thoracic Wall/surgery , Thoracic Wall/microbiology , Lung Diseases, Fungal/surgery , Lung Diseases, Fungal/diagnosis , Debridement/methods , Male , Antifungal Agents/therapeutic use , Tomography, X-Ray Computed , Immunocompromised Host
5.
Iran J Med Sci ; 49(7): 450-460, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39114634

ABSTRACT

Background: Following the coronavirus disease 2019 outbreak (COVID-19), it became a worrisome health burden worldwide. COVID-19-associated mucormycosis emergence, characterized by dysregulated inflammation and iron metabolism, exacerbated the prognosis of affected patients. Given the significance of hepcidin in regulating inflammation and iron metabolism, this study investigated the significance of hepcidin single nucleotide polymorphisms (SNP) in COVID-19-associated mucormycosis development, along with the association between the clinical and laboratory factors and COVID-19-associated mucormycosis. Methods: From September 2021 to November 2021, COVID-19 patients with and without mucormycosis were enrolled in this cross-sectional study. Their medical records and laboratory results were investigated. SNP genotyping was performed using Sanger sequencing. Hardy-Weinberg Equilibrium, Pearson's Chi square, and student t test were used for analyzing the data using SPSS software version 25. P<0.05 was regarded as statistically significant. Results: Here, 110 COVID-19 patients with and without mucormycosis were investigated. Elevated levels of urea, aspartate aminotransferase, lactate dehydrogenase, and increased ratio of polymorphonuclear neutrophil to lymphocytes were associated with decreased risk of COVID-19-associated mucormycosis in patients (all P<0.05). Moreover, diabetes mellitus increased the risk of mucormycosis (P=0.028). In contrast to patients without mucormycosis, patients with mucormycosis did not display 442 GA and SNP335 GT genotypes. Unlike patients without mucormycosis, none of the patients with mucormycosis had SNP442 GA and SNP335 GT genotypes. Regarding SNP 443 C>T, and the combination of SNPs 582 A>G and 443 C>T, CC genotype and AA+CC genotypes were associated with increased lactate dehydrogenase levels in COVID-19 patients, respectively. Conclusion: Regarding SNP 443 C>T, the CC genotype was associated with increased lactate dehydrogenase levels in COVID-19 patients. In terms of SNP 582 A>G and SNP 443 C>T, COVID-19 patients with AA+CC genotypes had higher levels of LDH. None of the patients with mucormycosis had SNP442 GA and SNP335 GT genotypes.


Subject(s)
COVID-19 , Hepcidins , Mucormycosis , Polymorphism, Single Nucleotide , Humans , COVID-19/genetics , COVID-19/complications , Female , Male , Middle Aged , Mucormycosis/complications , Cross-Sectional Studies , Hepcidins/genetics , Genetic Predisposition to Disease , Adult , Aged , SARS-CoV-2
6.
Ther Adv Respir Dis ; 18: 17534666241267242, 2024.
Article in English | MEDLINE | ID: mdl-39113423

ABSTRACT

Mucormycosis is an invasive fungal infection that can result in severe lung infections, with pulmonary mucormycosis (PM) being one of the most prevalent manifestations. Prompt diagnosis is crucial for patient survival, as PM often exhibits rapid clinical progression and carries a high fatality rate. Broncho-alveolar lavage fluid or endobronchial biopsy (EBB) has been commonly employed for diagnosing PM, although there is limited mention of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the literature. In this report, we present a case of PM in a patient with diabetes. While EBB did not yield evidence of Rhizopus infection, a definitive diagnosis was obtained through EBUS-TBNA. The patient underwent combination therapy, including oral medication, nebulization, and EBUS-guided intrafocal amphotericin B injection, which resulted in significant improvement following the failure of initial therapy with amphotericin B injection cholesterol sulfate complex. Our case highlights the potential of EBUS-TBNA not only for mediastinal lymphadenopathy but also for obtaining extraluminal lesion specimens. Furthermore, for patients with an inadequate response to mono-therapy and no access to surgical therapy, the addition of EBUS-guided intralesional amphotericin B injection to systemic intravenous therapy may yield unexpected effects.


Subject(s)
Amphotericin B , Antifungal Agents , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Lung Diseases, Fungal , Mucormycosis , Humans , Amphotericin B/administration & dosage , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Antifungal Agents/administration & dosage , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/microbiology , Male , Treatment Outcome , Injections, Intralesional , Middle Aged , Bronchoscopy
7.
Mycopathologia ; 189(4): 71, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39088077

ABSTRACT

INTRODUCTION: New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis. METHODS: We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis. RESULTS: Ninety-five patients were included, with "proven" (n = 27), "probable" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and "possible" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality. CONCLUSIONS: Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits.


Subject(s)
Amphotericin B , Antifungal Agents , Hematologic Diseases , High-Throughput Nucleotide Sequencing , Mucormycosis , Humans , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Mucormycosis/mortality , Mucormycosis/microbiology , Male , Female , Retrospective Studies , Middle Aged , Prognosis , Antifungal Agents/therapeutic use , Adult , Aged , Hematologic Diseases/complications , Amphotericin B/therapeutic use , Metagenomics/methods , Triazoles/therapeutic use , Young Adult , Drug Therapy, Combination , Survival Analysis , Treatment Outcome
8.
Dermatol Online J ; 30(2)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38959919

ABSTRACT

Primary cutaneous mucormycosis is caused by environmental fungi and may complicate leg ulcers or traumatic wounds even in immunocompetent individuals. This case report highlights recurrent lower limb ulcers and cellulitis in a patient with type two diabetes mellitus, which was unresponsive to conventional antibiotic treatment. Histopathology revealed the diagnosis of cutaneous mucormycosis, and fungal cultures identified Rhizopus variabilis as the causative organism. Initial courses of oral azole antifungals yielded only partial response and he eventually required more aggressive treatment with i.v. amphotericin B and oral posaconazole. Good treatment outcomes for this condition require a high index of clinical suspicion, early histopathological and microbiological diagnosis, targeted systemic antifungal therapy, and surgical debridement if necessary.


Subject(s)
Antifungal Agents , Cellulitis , Dermatomycoses , Diabetes Mellitus, Type 2 , Leg Ulcer , Mucormycosis , Humans , Mucormycosis/diagnosis , Mucormycosis/complications , Cellulitis/microbiology , Cellulitis/drug therapy , Male , Diabetes Mellitus, Type 2/complications , Antifungal Agents/therapeutic use , Leg Ulcer/microbiology , Dermatomycoses/diagnosis , Dermatomycoses/drug therapy , Dermatomycoses/pathology , Rhizomucor/isolation & purification , Amphotericin B/therapeutic use , Recurrence , Middle Aged , Triazoles/therapeutic use , Rhizopus/isolation & purification
10.
Am J Otolaryngol ; 45(5): 104392, 2024.
Article in English | MEDLINE | ID: mdl-39047622

ABSTRACT

OBJECTIVES: To evaluate surgical outcomes of invasive fungal rhinosinusitis MATERIALS AND METHODS: The National Inpatient Sample Database (2000-2015 Q3) was queried for patients with a diagnosis of aspergillosis and/or mucormycosis and a diagnosis of acute sinusitis using the International Classification of Diseases, Ninth Edition. Factors associated with inpatient mortality were then identified with multivariate logistic regression. RESULTS: 514 adult patients with a median age of 57.0 years were identified, of which 231 (44.9 %) underwent sinus surgery. Surgical patients had a longer length of stay (17.0 vs 9.0 days, p < 0.001) and higher total charges ($139,762.00 vs $57,945.00, p < 0.001). The number of sinus procedures was associated with reduced odds of inpatient mortality (OR 0.69; p < 0.001) in multivariate analysis. Hypertension (OR 0.34, p = 0.002) and chronic kidney disease (OR 0.23, p = 0.034) were associated with reduced odds of inpatient mortality. Total number of procedures (OR 1.24; p = 0.002), mucormycosis (OR 2.75, p = 0.002), age (OR 1.03, p = 0.006) and acid-base disorders (OR 2.85, p = 0.012) were associated with increased odds of inpatient mortality. CONCLUSION: This represents the first large scale study to evaluate outcomes for invasive fungal rhinosinusitis. These findings suggest the odds of inpatient mortality decrease with greater extent of sinus surgery performed. The potentially protective roles of hypertension and chronic kidney disease should be evaluated in future research.


Subject(s)
Aspergillosis , Hospital Mortality , Mucormycosis , Rhinitis , Sinusitis , Humans , Sinusitis/surgery , Sinusitis/mortality , Sinusitis/microbiology , Middle Aged , Male , Female , Rhinitis/surgery , Rhinitis/mortality , Rhinitis/microbiology , Mucormycosis/mortality , Mucormycosis/surgery , Aspergillosis/mortality , Aspergillosis/surgery , Aged , Adult , Invasive Fungal Infections/mortality , Invasive Fungal Infections/surgery , Length of Stay/statistics & numerical data , Hypertension/complications , Hypertension/mortality , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/complications , Treatment Outcome , Rhinosinusitis
11.
Diagn Microbiol Infect Dis ; 110(2): 116463, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39059149

ABSTRACT

This study aimed to design and evaluate a universal primer for Polymerase Chain Reaction (PCR)- based detection of mucormycosis-causing fungi by targeting their Internal Transcribed Spacer (ITS) sequences. In-silico analysis was conducted to assess primer suitability. Using Clustal Omega and Primer-BLAST, ITS sequences of 32 fungi species causing mucormycosis were aligned and subjected to primer design. Generated primers were sorted and in silico PCR simulations were performed to identify primers capable of amplifying all fungal species. Instead of identifying one pair of universal primer, in silico PCR analysis identified a panel of 14 primer pairs designed from full-length ITS sequences, and a panel of 12 primer pairs designed from conserved regions, that could detect 31 species. The study recommends a panel of 12 primers for multiplex-PCR to detect mucormycosis-causing fungi instead of a long list of PCR analyses for each fungus in diagnosing mucormycosis.


Subject(s)
DNA Primers , DNA, Fungal , Mucormycosis , Mucormycosis/diagnosis , Mucormycosis/microbiology , Humans , DNA Primers/genetics , DNA, Fungal/genetics , Computer Simulation , DNA, Ribosomal Spacer/genetics , Polymerase Chain Reaction/methods , Molecular Diagnostic Techniques/methods , Multiplex Polymerase Chain Reaction/methods
12.
Indian J Med Microbiol ; 50: 100661, 2024.
Article in English | MEDLINE | ID: mdl-38950657

ABSTRACT

Rhino-orbital-cerebral mucormycosis (ROCM) is linked to uncontrolled diabetes, diabetic ketoacidosis, iron overload, corticosteroid therapy, and neutropenia. This study evaluated a commercial real-time PCR system's effectiveness in detecting Mucorales from nasal swabs in 50 high-risk patients. Nasal swab PCR showed 30% positivity, compared to 8% with KOH microscopy. Despite its improved sensitivity, nasal swab PCR has limitations, highlighting the importance of established sampling methods in mucormycosis diagnosis. Participants were predominantly male (64%), with diabetes (78%) and amphotericin B use (96%). Prior COVID-19 was 42%, with 30% positive for Mucorales by PCR, compared to 8% with KOH microscopy.


Subject(s)
Mucorales , Mucormycosis , Real-Time Polymerase Chain Reaction , Humans , Mucormycosis/diagnosis , Male , Female , Real-Time Polymerase Chain Reaction/methods , Mucorales/isolation & purification , Mucorales/genetics , Middle Aged , Adult , COVID-19/diagnosis , Sensitivity and Specificity , Aged , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
14.
mBio ; 15(8): e0014424, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-38953355

ABSTRACT

Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous Mucorales. Under appropriate thermal conditions, mononuclear yeast forms alternate with multi-nucleate hyphae. Here, we describe a dimorphic mucoralean fungus obtained from the sputum of a patient with Burkitt lymphoma and ongoing graft-versus-host reactions. The fungus is described as Mucor germinans sp. nov. Laboratory studies were performed to simulate temperature-dependent dimorphism, with two environmental strains Mucor circinelloides and Mucor kunryangriensis as controls. Both strains could be induced to form multinucleate arthrospores and subsequent yeast-like cells in vitro. Multilateral yeast cells emerge in all three Mucor species at elevated temperatures. This morphological transformation appears to occur at body temperature since the yeast-like cells were observed in the lungs of our immunocompromised patient. The microscopic appearance of the yeast-like cells in the clinical samples is easily confused with that of Paracoccidioides. The ecological role of yeast forms in Mucorales is discussed.IMPORTANCEMucormycosis is a devastating disease with high morbidity and mortality in susceptible patients. Accurate diagnosis is required for timely clinical management since antifungal susceptibility differs between species. Irregular hyphal elements are usually taken as the hallmark of mucormycosis, but here, we show that some species may also produce yeast-like cells, potentially being mistaken for Candida or Paracoccidioides. We demonstrate that the dimorphic transition is common in Mucor species and can be driven by many factors. The multi-nucleate yeast-like cells provide an effective parameter to distinguish mucoralean infections from similar yeast-like species in clinical samples.


Subject(s)
Mucor , Mucormycosis , Humans , Mucormycosis/microbiology , Mucormycosis/diagnosis , Mucor/isolation & purification , Mucor/genetics , Mucor/classification , Paracoccidioides/isolation & purification , Paracoccidioides/genetics , Sputum/microbiology , Phylogeny , DNA, Fungal/genetics , DNA, Fungal/chemistry , Immunocompromised Host , Male , Sequence Analysis, DNA , Temperature
15.
mBio ; 15(8): e0166124, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-38980037

ABSTRACT

Mucormycoses are emerging fungal infections caused by a variety of heterogeneous species within the Mucorales order. Among the Mucor species complex, Mucor circinelloides is the most frequently isolated pathogen in mucormycosis patients and despite its clinical significance, there is an absence of established genome manipulation techniques to conduct molecular pathogenesis studies. In this study, we generated a spontaneous uracil auxotrophic strain and developed a genetic transformation procedure to analyze molecular mechanisms conferring antifungal drug resistance. With this new model, phenotypic analyses of gene deletion mutants were conducted to define Erg3 and Erg6a as key biosynthetic enzymes in the M. circinelloides ergosterol pathway. Erg3 is a C-5 sterol desaturase involved in growth, sporulation, virulence, and azole susceptibility. In other fungal pathogens, erg3 mutations confer azole resistance because Erg3 catalyzes the production of a toxic diol upon azole exposure. Surprisingly, M. circinelloides produces only trace amounts of this toxic diol and yet, it is still susceptible to posaconazole and isavuconazole due to alterations in membrane sterol composition. These alterations are severely aggravated by erg3Δ mutations, resulting in ergosterol depletion and, consequently, hypersusceptibility to azoles. We also identified Erg6a as the main C-24 sterol methyltransferase, whose activity may be partially rescued by the paralogs Erg6b and Erg6c. Loss of Erg6a function diverts ergosterol synthesis to the production of cholesta-type sterols, resulting in resistance to amphotericin B. Our findings suggest that mutations or epimutations causing loss of Erg6 function may arise during human infections, resulting in antifungal drug resistance to first-line treatments against mucormycosis. IMPORTANCE: The Mucor species complex comprises a variety of opportunistic pathogens known to cause mucormycosis, a potentially lethal fungal infection with limited therapeutic options. The only effective first-line treatments against mucormycosis consist of liposomal formulations of amphotericin B and the triazoles posaconazole and isavuconazole, all of which target components within the ergosterol biosynthetic pathway. This study uncovered M. circinelloides Erg3 and Erg6a as key enzymes to produce ergosterol, a vital constituent of fungal membranes. Absence of any of those enzymes leads to decreased ergosterol and consequently, resistance to ergosterol-binding polyenes such as amphotericin B. Particularly, losing Erg6a function poses a higher threat as the ergosterol pathway is channeled into alternative sterols similar to cholesterol, which maintain membrane permeability. As a result, erg6a mutants survive within the host and disseminate the infection, indicating that Erg6a deficiency may arise during human infections and confer resistance to the most effective treatment against mucormycoses.


Subject(s)
Antifungal Agents , Biosynthetic Pathways , Drug Resistance, Fungal , Ergosterol , Mucor , Ergosterol/biosynthesis , Ergosterol/metabolism , Antifungal Agents/pharmacology , Drug Resistance, Fungal/genetics , Biosynthetic Pathways/genetics , Humans , Mucor/genetics , Mucor/drug effects , Mucor/metabolism , Mucormycosis/microbiology , Mucormycosis/drug therapy , Microbial Sensitivity Tests , Triazoles/pharmacology , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Deletion , Nitriles/pharmacology , Pyridines/pharmacology , Oxidoreductases
16.
Microbiology (Reading) ; 170(7)2024 Jul.
Article in English | MEDLINE | ID: mdl-39073411

ABSTRACT

Mucormycosis is an emerging and deadly invasive fungal infection caused by fungi belonging to the Mucorales order. We investigated the myosin superfamily, which encompasses diverse actin-based motor proteins with various cellular functions. Specifically, the role of the Myo5B (ID 179665) protein from the myosin class V family in Mucor lusitanicus was explored by generating silencing phenotypes and null mutants corresponding to the myo5B gene. Silencing fungal transformants exhibited a markedly reduced growth rate and a nearly complete absence of sporulation compared to the wild-type strain. The myo5BΔ null mutant strain displayed atypical characteristics, including abnormally short septa and inflated hyphae. Notably, there were a majority of small yeast-like cells instead of filamentous hyphae in the mutant. These yeast-like cells cannot germinate normally, resulting in a loss of polarity. In vivo virulence assays conducted in the Galleria mellonella invertebrate model revealed that the myo5BΔ mutant strain was avirulent. These findings shed light on the crucial contributions of the Myo5B protein to the dimorphism and pathogenicity of M. lusitanicus. Therefore, the myosin V family is a potential target for future therapeutic interventions aimed at treating mucormycosis.


Subject(s)
Fungal Proteins , Hyphae , Mucor , Hyphae/growth & development , Hyphae/genetics , Mucor/genetics , Mucor/pathogenicity , Mucor/growth & development , Virulence , Animals , Fungal Proteins/genetics , Fungal Proteins/metabolism , Myosin Type V/genetics , Myosin Type V/metabolism , Mucormycosis/microbiology , Moths/microbiology , Humans , Spores, Fungal/growth & development , Spores, Fungal/genetics
17.
Front Cell Infect Microbiol ; 14: 1375058, 2024.
Article in English | MEDLINE | ID: mdl-39081868

ABSTRACT

Rhino-orbital-cerebral mucormycosis (ROCM) is a rare, invasive, and fatal fungal disease that is often easily misdiagnosed in the early stages due to the lack of specific clinical manifestations and adequate auxiliary examinations. Early diagnosis and timely therapy are essential for successful treatment. In this report, we presented a 46-year-old man with diabetes who experienced gradual vision loss, right ptosis, swelling, and headaches that progressively worsened to death within 4 days after admission. It was finally confirmed as a fungal Rhizopus arrhizus infection by metagenomics next-generation sequencing (mNGS). Our report has proved that mNGS testing should be strongly recommended in highly suspected patients.


Subject(s)
High-Throughput Nucleotide Sequencing , Metagenomics , Mucormycosis , Rhizopus , Humans , Mucormycosis/diagnosis , Mucormycosis/microbiology , Male , Rhizopus/genetics , Rhizopus/isolation & purification , Middle Aged , Metagenomics/methods , Fatal Outcome , Orbital Diseases/diagnosis , Orbital Diseases/microbiology , Antifungal Agents/therapeutic use
18.
Article in English | MEDLINE | ID: mdl-39052028

ABSTRACT

Mucormycosis is a rare life-threatening opportunistic infection, with rhinocerebral mucormycosis (ROCM) being the most common presentation. Trichosporon asahii is an emerging pathogen that often causes fatal infections in patients with underlying hematologic malignancies due to its high drug resistance. We report a rare case of concomitant rhinocerebral mucormycosis and T. asahii fungemia secondary to Pseudomonas aeruginosa sepsis in a patient with neutropenia and acute lymphoblastic leukemia. A boy aged one year and two months was diagnosed with B-cell acute lymphoblastic leukemia on January 10 and underwent three courses of regular chemotherapy. He experienced neutropenia for 154 days and was hospitalized for vomiting, diarrhea and fever for 3 days. The day after hospitalization, Pseudomonas aeruginosa was isolated by blood culture and ceftazidime/avibactam was administered. Extracorporeal Membrane Oxygenation (ECMO) was used to provide continuous extracorporeal respiration and circulation for the patient. On day 8, the patient developed T. asahii fungemia. On day 10, he presented with necrotizing skin caused by Rhizopus delemar. He was treated with liposomal amphotericin B for Rhizopus delemar and voriconazole for T. asahii infection. Unfortunately, his health deteriorated and he died on day 11 due to the rapid progression of the infection and multiple organ failure. The management and treatment of such a complex infection requires a multidisciplinary approach and close monitoring of the patient's condition. Therefore, it is imperative to continue to research and report rare cases such as this to further understand the complexities of mucormycosis and trichosporidiosis coinfection and improve patient outcomes.


Subject(s)
Coinfection , Fungemia , Mucormycosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Trichosporonosis , Humans , Male , Mucormycosis/complications , Mucormycosis/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Fungemia/microbiology , Fungemia/drug therapy , Fatal Outcome , Coinfection/microbiology , Trichosporonosis/microbiology , Trichosporonosis/diagnosis , Trichosporonosis/drug therapy , Infant , Opportunistic Infections/microbiology , Opportunistic Infections/complications , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas Infections/complications , Antifungal Agents/therapeutic use , Basidiomycota
20.
Front Cell Infect Microbiol ; 14: 1368165, 2024.
Article in English | MEDLINE | ID: mdl-38915923

ABSTRACT

Background: Mucormycosis is an uncommon invasive fungal infection that has a high mortality rate in patients with severe underlying diseases, which leads to immunosuppression. Due to its rarity, determining the incidence and optimal treatment methods for mucormycosis in children is challenging. Metagenomic next-generation sequencing (mNGS) is a rapid, precise and sensitive method for pathogen detection, which helps in the early diagnosis and intervention of mucormycosis in children. In order to increase pediatricians' understanding of this disease, we conducted a study on the clinical features of mucormycosis in children and assessed the role of mNGS in its diagnosis. Methods: We retrospectively summarized the clinical data of 14 children with mucormycosis treated at the First Affiliated Hospital of Zhengzhou University from January 2020 to September 2023. Results: Of the 14 cases, 11 case of mucormycosis were classified as probable, and 3 cases were proven as mucormycosis. Most children (85.71%) had high-risk factors for mucormycosis. All 14 children had lung involvement, with 5 cases of extrapulmonary dissemination. Among the 14 cases, 4 cases underwent histopathological examination of mediastinum, lung tissue or kidney tissue, in which fungal pathogens were identified in 3 patients. Fungal hyphae was identified in 3 cases of mucormycosis, but only 1 case yielded a positive culture result. All patients underwent mNGS testing with samples from blood (8/14), bronchoalveolar lavage fluid (6/14), and tissue (1/14). mNGS detected fungi in all cases: 7 cases had Rhizomucor pusillus, 4 cases had Rhizopus oryzae, 3 cases had Rhizopus microsporus, 1 case had Lichtheimia ramosa, and 1 case had Rhizomucor miehei. Coinfections were found with Aspergillus in 3 cases, bacteria in 3 cases, and viruses in 5 cases. Conclusion: Children with mucormycosis commonly exhibit non-specific symptoms like fever and cough during the initial stages. Early diagnosis based on clinical symptoms and imaging is crucial in children suspected of having mucormycosis. mNGS, as a supplementary diagnostic method, offers greater sensitivity and shorter detection time compared to traditional mucormycosis culture or histopathological testing. Additionally, mNGS enables simultaneous detection of bacteria and viruses, facilitating timely and appropriate administration of antibiotics and thereby enhancing patient outcomes.


Subject(s)
High-Throughput Nucleotide Sequencing , Metagenomics , Mucormycosis , Humans , Mucormycosis/diagnosis , Mucormycosis/microbiology , High-Throughput Nucleotide Sequencing/methods , Male , Female , Child , Child, Preschool , Metagenomics/methods , Retrospective Studies , Infant , Adolescent , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/microbiology , China
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