Search Results (143)

Mucormycosis is a life-threatening infection caused by fungi of the Mucorales order, typically associated with immunocompromised hosts, but increasingly reported in immunocompetent individuals. This study investigated fungal burden, Th1/Th17 inflammatory profiles, and organ-specific dynamics in immunocompetent BALB/c mice intravenously infected with Rhizopus oryzae, Mucor circinelloides, or Rhizomucor pusillus. Colony-forming units were quantified in spleen, liver, and kidney at multiple time points, while serum cytokines and oxidative stress markers were analyzed. The results showed fungal persistence primarily in the spleen, accompanied by species-specific Th1/Th17 responses: R. oryzae induced the highest inflammatory response among all groups, with maximal cytokine production observed on day 7, particularly for IL-17A (352.58 pg/mL). In contrast, M. circinelloides exhibited its peak cytokine levels earlier, reaching the highest TNF-α concentration on day 3 (425.43 pg/mL). Meanwhile, R. pusillus triggered an early but moderate inflammatory response, with a maximum TNF-α value of 372.62 pg/mL detected on day 1, followed by clearance. Correlation analysis highlighted distinct immunological patterns, with IL-10 acting as a negative regulator of inflammation, while TNF-α and IL-17A reflected infection intensity depending on species and timing. The spleen emerged as a key organ coordinating immune responses during systemic infection. These findings reveal that mucormycosis in immunocompetent hosts triggers complex, species-dependent immune dynamics beyond classical immunosuppression, emphasizing the need to consider host–pathogen interactions when developing targeted antifungal strategies. Full article

Background: The frequency of necrotising cutaneous and soft tissue infections caused by the Mucorales fungi Apophysomyces and Sakasenaea is increasing. The absence of sophisticated diagnostic technologies in low- and middle-income countries (LMICs) means that detection of cutaneous mucormycosis continues to rely on culture of the infecting pathogens from biopsy and their differentiation based on morphological characteristics. However, Apophysomyces and Sakasenaea are notorious for their failure to sporulate on standard mycological media used for the identification of human pathogenic fungi. Differentiation of these pathogens and their discrimination from Aspergillus fumigatus, the most common mould pathogen of humans, is essential due to their differing sensitivities to the antifungal drugs used to treat mucormycosis. Methods: A murine IgG1 monoclonal antibody, JD4, has been developed that is specific to Apophysomyces species. In Western blotting and enzyme-linked immunosorbent assay (ELISA), mAb JD4 is shown to bind to an extracellular 15 kDa protein, readily detectable in crude antigen extracts from non-sporulating cultures of Apophysomyces. Results: When combined with a Mucorales-specific lateral-flow immunoassay (LFIA), mAb JD4 allows the differentiation of Apophysomyces from Saksenaea species and discrimination from Aspergillus fumigatus. Monoclonal antibody JD4 enables the detection and differentiation of Apophysomyces species from other fungal pathogens that cause rapidly progressive cutaneous and soft tissue mycoses in humans. When this is combined with a rapid LFIA, improvements are offered in the sensitivity and specificity of Mucorales detection based on mycological culture, which remains a gold-standard procedure for mucormycosis detection in LMICs lacking access to more sophisticated diagnostic procedures. Full article

Mucor species are fast-growing filamentous fungi, widespread in natural ecosystems. As opportunistic pathogens, some species can cause mucormycoses in humans and animals, while others hold significant economic value in food fermentation and bioengineering. In this study, four novel species were identified from soil samples collected in Xizang Autonomous Region and Yunnan Province, China, and their establishment as new species was supported by morphological characteristics and molecular data (ITS-LSU-RPB1), with phylogenetic analyses conducted using the Maximum Likelihood (ML) and Bayesian Inference (BI) methods. M. globosporus sp. nov. is characterized by producing globose chlamydospores. M. multimorphus sp. nov. is distinguished by swelling in the sporangiophores. M. polymorphus sp. nov. is differentiated by polymorphic chlamydospores. And M. xizangensis sp. nov. reflects its geographical origin in the Xizang Autonomous Region. Comprehensive descriptions of each novel taxon are presented herein. This study constitutes the ninth segment in an ongoing series elucidating early-diverging fungal diversity in China, expanding the understanding of the phylogeny of Mucor fungi and extending the worldwide number of known Mucor species to 137. Full article

Mucormycosis is a rare invasive fungal disease in pediatric patients with hematological malignancies and is associated with poor outcomes. We present a fulminant and ultimately fatal case of rhino-orbito-cerebral mucormycosis, addressing important issues including clinical signs and symptoms, diagnostic approaches and the challenges of timely diagnosis. The patient was an 11-year old girl undergoing re-induction chemotherapy for Central Nervous System relapse of B-cell precursor acute lymphoblastic leukemia. She presented six days into the second course of chemotherapy in profound neutropenia with aggravating headaches, painful abducens nerve palsy and anisocoria. At first (day −3), no significant radiological or ophthalmological correlations were found, and methyl–prednisolone was started due to suspected vasculitis following ICU admission. After further clinical deterioration, a second MRI scan (day 0) revealed a prolonged occlusion of the left carotid artery, which was successfully stented in a neuroradiological intervention (day +1). However, during the next day the child developed clinical signs indicating severe cerebral dysfunction. An emergency CT scan showed complete infarction of the left hemisphere including a progredient perfusion deficit and beginning brain edema. Based on the unfavorable prognosis, best supportive care was initiated, and the patient deceased on day +2. Pathological and microbiological workup identified thrombotic infarction in all major cerebral arteries. While microscopy was suspicious for mucormycosis, nested PCR from retained blood specimens confirmed the genus Lichtheimia. Final NGS on brain tissue led to the identification of Lichtheimia ramosa. This case illustrates the rapidity and severity of Mucorales infection. It shows the importance of early clinical suspicion and the need for an aggressive laboratory testing algorithms. The stratification of risk factors and definition of red flags may be a future task fighting these infections. Full article

Background: Polymerase chain reaction (PCR) is highly sensitive and specific for the rapid diagnosis of invasive fungal disease (IFD) but is not yet widely implemented due to concerns regarding limited standardisation between assays, the lack of commercial options and the absence of clear guidance on interpreting results. Objectives and Methods: This review provides an update on technical and clinical aspects of PCR for the diagnosis of the most pertinent fungal pathogens, including Aspergillus, Candida, Pneumocystis jirovecii, Mucorales spp., and endemic mycoses. Summary: Recent meta-analyses have demonstrated that quantitative PCR (qPCR) offers high sensitivity for diagnosing IFD, surpassing conventional microscopy, culture and most serological tests. The reported specificity of qPCR is likely underestimated due to comparison with imperfect reference standards with variable sensitivity. Although the very low limit of detection of qPCR can generate false positive results due to procedural contamination or patient colonisation (particularly in pulmonary specimens), the rates are comparable to those observed for biomarker testing. When interpreting qPCR results, it is essential to consider the pre-test probability, determined by the patient population, host factors, clinical presentation and risk factors. For patients with low to moderate pre-test probability, the use of sensitive molecular tests, often in conjunction with serological testing or biomarkers, can effectively exclude IFD when all tests return negative results, reducing the need for empirical antifungal therapy. Conversely, for patients with high pre-test probability and clinical features of IFD, qPCR testing on invasive specimens from the site of infection (such as tissue or bronchoalveolar lavage fluid) can confidently rule in the disease. The development of next-generation sequencing methods to detect fungal infection has the potential to enhance the diagnosis of IFD, but standardisation and optimisation are essential, with improved accessibility underpinning clinical utility. Full article

Absidia is the most species-rich genus within the family Cunninghamellaceae, with its members commonly isolated from diverse substrates, particularly rhizosphere soil. In this study, four novel Absidia species, A. irregularis sp. nov., A. multiformis sp. nov., A. ovoidospora sp. nov., and A. verticilliformis sp. nov., were discovered from soil samples collected in southern and southwestern China, using integrated morphological and molecular analyses. Phylogenetic analyses based on concatenated ITS, SSU, LSU, Act, and TEF1α sequence data reconstructed trees that strongly supported the monophyly of each of these four new taxa. Key diagnostic features include A. irregularis (closely related to A. oblongispora) exhibiting irregular colony morphology, A. multiformis (sister to A. heterospora) demonstrating polymorphic sporangiospores, A. ovoidospora (forming a clade with A. panacisoli and A. abundans) producing distinctive ovoid sporangiospores, and A. verticilliformis (next to A. edaphica) displaying verticillately branched sporangiophores. Each novel species is formally described with comprehensive documentation, including morphological descriptions, illustrations, Fungal Names registration identifiers, designated type specimens, etymological explanations, maximum growth temperatures, and taxonomic comparisons. This work constitutes the sixth instalment in a series investigating early-diverging fungal diversity in China aiming to enhance our understanding of the diversity of fungi in tropical and subtropical ecosystems in Asia. In this paper, the known species of Absidia are expanded to 71. Full article

The fungal genus Cunninghamella, ubiquitously distributed as saprotrophic organisms with occasional endophytic and phytopathogenic manifestations, holds significant biomedical and biochemical importance. During systematic investigations of fungal biodiversity in China, seven novel taxa (C. amphispora sp. nov., C. cinerea sp. nov., C. flava sp. nov., C. hainanensis sp. nov., C. rhizoidea sp. nov., C. simplex sp. nov., and C. yunnanensis sp. nov.) were delineated through integrated taxonomic approaches incorporating morphological characterization, multilocus phylogenetic analyses (ITS-LSU-TEF1α), and physiological assessments. Phylogenetic reconstructions positioned these novel species within a well-supported clade along with C. bainieri and C. verticillata. New species and their diagnostic features are C. amphispora, exhibiting dimorphic sporangiola production; C. cinerea, distinguished by gray pigmentation in the colony; C. flava, characterized by a yellow colony; C. hainanensis and C. yunnanensis, bearing eponymous designations reflecting their geographic origins; and C. simplex, displaying simplified sporangiophore branching. Comprehensive taxonomic descriptions accompanied by photomicrographic illustrations are provided herein. This study constitutes the seventh installment in an ongoing series elucidating early-diverging fungal diversity in China, expanding the global Cunninghamella taxonomic inventory to 63 species and advancing our understanding of mucoralean phylogeny. Full article

Hepatic mucormycosis is a rare but often fatal opportunistic fungal infection, primarily affecting immunocompromised patients. Herein, we report such a case from MD Anderson Cancer Center (Houston, TX, USA) and systematically review published cases in patients ≥ 19 years of age to better characterize clinical presentation, diagnostic challenges, and treatment outcomes of hepatic mucormycosis. Among the 40 identified cases (including ours), hematologic malignancies (55%) and solid organ transplantation (30%) were the most common underlying conditions. Fever (70%) and abdominal pain (63%) were the predominant symptoms. Imaging revealed multiple hepatic lesions in 72% of cases. Diagnosis was primarily based on histopathology (73%), whereas culture positivity was low (36%), underscoring the difficulty of pathogen isolation. Mucorales-active antifungal therapy was often delayed but eventually used in 85% of cases (all amphotericin B +/− Mucorales-active triazoles), while 45% underwent additional surgical intervention. Despite treatment, 1-year all-cause mortality remained high at 46%, with a trend towards lower mortality for those who underwent surgery compared to non-surgical management (35% vs. 55%, p = 0.334). These findings highlight the aggressive nature of hepatic mucormycosis and the importance of early recognition as well as the need for non-culture-based diagnostics and multimodal treatment approaches. Improved awareness and further research into optimized management strategies are crucial to improve the outcomes of this challenging infection. Full article

In eukaryotes, the mitogen-activated protein kinase (MAPK) cascade pathway is a highly conserved cell signaling mechanism that is essential for stress response, growth, and development. MAPK cascade genes have currently been identified and characterized in a wide range of fungi, although they have not been fully understood in early divergent fungal lineages like the Mucoromycota, which contains Mucoromycotina, Glomeromycotina, and Mortierellomycotina. In this study, a genome-wide investigation of Blakeslea trispora (Mucorales, Choanephoraceae) revealed a total of 19 MAPK cascade genes, including 9 BtMAPKKKs, 4 BtMAPKKs, and 6 BtMAPKs genes. Using phylogenetic analysis, it was found that the kinase domain sequences and motif composition of the three MAPK, MAPKK, and MAPKKK lineages are substantially conserved in fungi. Whole genome duplication analysis indicated that B. trispora has four and nine duplication pairs in the MAPK and MAPKKK genes, respectively, which are expanded by segmental replication events. BtHog2, the orthologous protein of Hog1, exhibits a substantial rise in transcription levels under blue light irradiation, indicating its function in light signal response and transduction. Several sets of interacting protein pairs were found using molecular docking analysis and yeast two-hybrid assay, providing a comprehensive MAPK cascade signaling network in B. trispore. Furthermore, MAPK cascade proteins show varying transcription levels in response to blue light and sex hormone stimulation, as well as variable treatment duration. BtMAPKKK9 and BtBck1 are strongly induced during sexual interaction, indicating their involvement in the response to trisporic acid and the subsequent alterations in hyphal cell wall structure. These findings shed light on the evolution of MAPK cascade genes and the functional mechanisms underlying MAPK cascade genes in response to light and sex hormone signaling pathways in B. trispore. Full article

Intra-abdominal and gastrointestinal mucormycosis are less frequent than rhino-orbito-cerebral and pulmonary mucormycosis, but highly lethal. Their diagnosis remains challenging due to the non-specific clinical presentation. We collected English-language cases of intra-abdominal and gastrointestinal mucormycosis in non-haematological and non-neonatal patients published up to October 2024. This review analysed the epidemiological, clinical, and therapeutic charts of 290 cases. A proportion of 53.4% were reported from India and the USA. The main predisposing conditions were diabetes, solid organ transplant, ICU, and corticosteroid treatment. The most common site was the stomach (53.8%). Gastrointestinal perforation, skin breakdown, and abdominal wall infection were sources of intra-abdominal localisation. The most common symptoms were abdominal pain, vomiting, and gastrointestinal bleeding. The diagnosis relied on histology (93.8%), mycology with microscopy and culture (38.8%), and molecular methods (9.9%). Mortality (52.9%) was lower when treatment was intravenous amphotericin B, combined or not with surgery. Prompt treatment, essential for a favourable outcome, relies on early suspicion and diagnosis. Gastrointestinal and intra-abdominal mucormycosis should also be suspected in patients admitted in ICU with ventilation/nasogastric tube and corticosteroids and those with abdominal trauma or surgery, presenting abdominal distension, pain, and GI bleeding. Mycological diagnosis including direct examination, culture and Mucorales qPCR on tissue should assist with rapid diagnosis and thus treatment. Full article

Background and Objectives: Secondary pulmonary fungal infections in coronavirus disease 2019 (COVID-19) remain underexplored despite emerging reports linking them to heightened morbidity. Comorbidities, steroid use, and prolonged hospital stays can predispose patients to opportunistic fungi. This study aimed to evaluate the impact of fungal coinfection on inflammatory markers, disease severity, antifungal resistance profiles, and outcomes in hospitalized COVID-19 patients. Methods: This retrospective observational study enrolled 280 adults (≥18 years) with real-time polymerase chain reaction (RT-PCR)-confirmed COVID-19 admitted to a tertiary care center (January 2023–December 2024). Patients were divided into a COVID-19-only group (n = 216) and a COVID–fungal group (n = 64) based on bronchoalveolar lavage, sputum, and/or blood culture positivity for fungal pathogens. Inflammatory markers (C-reactive protein (CRP), procalcitonin, the neutrophil-to-lymphocyte ratio, and the systemic immune inflammation index) and severity scores (Acute Physiology and Chronic Health Evaluation II, CURB-65 score, and the National Early Warning Score) were measured. We assessed antifungal susceptibilities and recorded ICU admissions, ventilation, hospital length of stay, and mortality. Results: Aspergillus fumigatus (31.3%), Candida albicans (28.1%), Cryptococcus neoformans (7.8%), Pneumocystis jirovecii (6.3%), and Mucorales (6.3%) dominated; Candida glabrata, Candida tropicalis, and mixed infections were also noted. Multidrug-resistant (MDR) isolates or resistance to triazoles occurred in 25.0% of cultures. The COVID-19–fungal group showed significantly higher CRP (85.7 vs. 71.6 mg/L, p < 0.001), procalcitonin (2.4 vs. 1.3 ng/mL, p < 0.001), and APACHE II scores (18.6 vs. 14.8, p < 0.001). intensive-care unit admissions (39.1% vs. 19.9%, p = 0.004) and mechanical ventilation (26.6% vs. 10.2%, p = 0.01) were more frequent with fungal coinfection. Mortality trended at a higher rate (15.6% vs. 7.4%, p = 0.06). Conclusions: Pulmonary fungal coinfections intensify the inflammatory milieu, elevate severity scores, and lead to more frequent ICU-level interventions in COVID-19 patients. Early identification, guided by culture-based and molecular diagnostics, alongside prompt antifungal therapy, could mitigate adverse outcomes. These findings underscore the critical need for proactive fungal surveillance and rigorous stewardship in managing severe COVID-19 pneumonia. Full article

We present the case of a 60-year-old immunocompromised man who presented with two pruritic pink–red indurated nodules with overlying scale and focal areas of ulceration on his left dorsal and left medial forearm, which evolved over a 2-month period. The pathology showed numerous fungal hyphae present that were pauci-septate with various branched angles and variable hyphal thickness. Fungal cultures grew Rhizopus species and a universal fungal PCR detected the Rhizopus oryzae complex. Based on the clinicopathologic correlation, the diagnosis of cutaneous mucormycosis was made. Cutaneous mucormycosis is an aggressive fungal infection of the Mucorales family occurring after the inoculation of fungal spores in disrupted skin. It usually presents as a necrotic eschar but can also present as cellulitis that evolves into a necrotic ulcer. A prompt diagnosis is critical for the effective management of cutaneous mucormycosis. The treatment includes an immediate systemic treatment with amphotericin B and a surgical debridement of the necrotic regions. Given the wide range of presenting symptoms, clinical suspicion for this emergent condition must remain high in immunocompromised and diabetic patients. Full article

Purpose: Mucormycosis is a rare but emerging and life-threatening infection caused by environmental mold, with a mortality rate of 30–70% despite progress in management. A better understanding could improve its management. Method: We conducted a single-center retrospective study of all cases of mucormycosis observed over a decade at the University Hospital of Caen. Results: Between 2014 and 2024, 18 cases of mucormycosis were identified, predominantly in males (n = 11, 65%). Most patients had hematological malignancies (n = 16, 89%). Seven cases were proven, and eleven were classified as probable. The main locations of infection were pulmonary (n = 12, 67%). Since 2021, we have observed an increase in the number of cases, rising from three between 2014 and 2021 to fifteen between 2021 and 2024. Among the 12 patients with pulmonary mucormycosis, all presented with fever except 1, and 67% required oxygen therapy. Chest computed tomography scans revealed an inverse halo sign in one-third of the patients. The first-line treatment consisted of amphotericin B in seventeen patients, posaconazole in one patient, and isavuconazole in one patient. Surgery was performed on seven patients. In cases of cutaneous mucormycosis, all patients underwent surgery, and none died within three months after the diagnosis. Overall, the three-month mortality rate was 39%. Surgical management was associated with a reduction in mortality (0% vs. 64%, p = 0.013). Conclusions: This study highlights the role of PCR for early diagnosis and the key role of surgery in improving clinical outcomes while underscoring the need for better-adapted therapeutic protocols for these rare infections. Full article