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The molecular composition and structural organisation of the cell wall of filamentous fungi underlie the ability of the host to identify them as pathogens. Although the organisation of the fungal cell wall, composed of 90% polysaccharides, is similar from one fungus to another, small variations condition their ability to trigger pattern recognition receptors. Because the incidence of mucormycosis, an emerging life-threatening infection caused by the species of the order Mucorales is increasing worldwide, the precise composition of the cell wall of two strains of Lichtheimia corymbifera was investigated in the early growth stages of germination (spores and germ-tubes) using trimethylsilylation and confocal microscopy. This study also characterises the response of THP-1 cells to Mucorales. The study identified the presence of uncommon monosaccharides (fucose, galactose and glucuronic acid) whose respective proportions vary according to the germination stage, revealing early parietal reorganisation. Immunofluorescence studies confirmed the exposure of β-glucan on the surface of swollen spores and germ-tubes. Both spores and germ-tubes of L. corymbifera promoted an early and strong pro-inflammatory response, through TLR-2. Our results show the singularity of the cell wall of the order Mucorales, opening perspectives for the development of specific diagnostic biomarkers.L. corymbifera is a causative agent of mucormycosis, an emerging invasive fungal infection. Deciphering cell wall composition can lead to the identification of a polysaccharide epitope, which could be use as a biomarker, useful for the diagnosis of mucormycosis.

We describe two fatal cases of COVID-19 in which Rhizopus microsporus and Lichtheimia corymbifera were cultured from endotracheal aspirate samples. Both patients had no underlying comorbidities other than obesity. Despite antifungal therapy, both cases developed septic shock and progressive refractory hypoxemia without evidence of other underlying infections. It is unclear whether isolation of these fungal organisms represents invasive disease or corresponds to an epiphenomenon of critical illness. Yet, patients suffering from COVID-19 may be at risk of superinfection from a broader range of fungal organisms than previously thought.

Fungal infections caused by the ancient lineage Mucorales are emerging and increasingly reported in humans. Comprehensive surveys on promising attributes from a multitude of possible virulence factors are limited and so far, focused on Mucor and Rhizopus. This study addresses a systematic approach to monitor phagocytosis after physical and enzymatic modification of the outer spore wall of Lichtheimia corymbifera, one of the major causative agents of mucormycosis. Episporic modifications were performed and their consequences on phagocytosis, intracellular survival and virulence by murine alveolar macrophages and in an invertebrate infection model were elucidated. While depletion of lipids did not affect the phagocytosis of both strains, delipidation led to attenuation of LCA strain but appears to be dispensable for infection with LCV strain in the settings used in this study. Combined glucano-proteolytic treatment was necessary to achieve a significant decrease of virulence of the LCV strain in Galleria mellonella during maintenance of the full potential for spore germination as shown by a novel automated germination assay. Proteolytic and glucanolytic treatments largely increased phagocytosis compared to alive resting and swollen spores. Whilst resting spores barely (1–2%) fuse to lysosomes after invagination in to phagosomes, spore trypsinization led to a 10-fold increase of phagolysosomal fusion as measured by intracellular acidification. This is the first report of a polyphasic measurement of the consequences of episporic modification of a mucormycotic pathogen in spore germination, spore surface ultrastructure, phagocytosis, stimulation of Toll-like receptors (TLRs), phagolysosomal fusion and intracellular acidification, apoptosis, generation of reactive oxygen species (ROS) and virulence.

Background Mucormycosis is a rare, invasive disease associated with high mortality rates, produced by opportunistic pathogens related to the Mucorales order and characterised by a diverse range of clinical forms; acute rhino-orbital-cerebral and pulmonary symptoms are the most reported ones. Objectives To report the experience of mucormycosis observed in a tertiary-care hospital in Mexico for 35 years. Methods This was a retrospective, descriptive and observational study on mucormycosis at a tertiary-care hospital in Mexico from January 1985 to December 2019. Demographic and clinical data and mycological and histopathological records were selected. Results Two hundred fourteen proven cases of mucormycosis for 35 years at a tertiary-care hospital in Mexico were included. Most of the cases were male patients with a median age of 45 years. The two most associated underlying diseases were diabetes mellitus (76.6%) and haematologic malignancy (15.4%). The three primary clinical forms were as follows: rhino-orbito-cerebral (75.9%), cutaneous (8.41%) and pulmonary (7.47%) mucormycosis. The most isolated agents were Rhizopus arrhizus (58.4%) and Lichtheimia corymbifera (12.3%). The overall therapeutic response was 58.5%, and the best response was observed with amphotericin B deoxycholate and surgical debridement. Conclusion Mucormycosis is an emerging disease, and its incidence has increased at our hospital over the years. In this study, the rhino-cerebral clinical type was the most frequent in patients with uncontrolled diabetes; the main aetiological agent was R. arrhizus. Early diagnosis, control of the underlying disease and prompt management may increase the survival rate.

The objective of this study was to investigate the probability of target attainment of various posaconazole dosing regimens against Mucorales species in patients with mucormycosis. According to pharmacokinetic/pharmacodynamic parameters of posaconazole in adults, the dosage regimen of posaconazole for mucormycosis included 50, 100, 200 and 400 mg orally q12h. Monte Carlo Simulation analysed the published parameters of pharmacokinetics and the MIC values of mucormycosis in Mucorales species. The results showed that posaconazole did not affect Rhizopus arrhizus and Mucor sp. The optimal dosage of posaconazole for Rhizopus microsporus and Rhizomucor pusillus was 400 mg orally q12h and the best dosage regimen for Lichtheimia corymbifera was 200 mg orally q12h. The antifungal activity of posaconazole against mucormycosis was different, and the dosage regimen needs to adjust according to fungal species.

As well as severe immunosuppression, other predisposing factors may facilitate invasive mycosis caused by molds. Chronic kidney disease and the resulting peritoneal dialysis have been reported as factors putting patients at risk of fungal infections from environmental sources. We describe an environmental investigation undertaken to guide exposure prevention for a peritoneal dialysis patient with transient colonization of her nostrils by Lichtheimia corymbifera in a rural area of northern Germany. Systematic screening for airborne and surface-deposited molds enabled targeted recommendations to be made, although Lichtheimia corymbifera itself was not grown from the collected environmental samples. This communication is intended to illustrate how such an investigation can be performed on the basis of the environmental distribution of the molds and how preventive recommendations can be derived from the results.

Alveolar macrophages (AM) are the first-line lung defense against Mucorales in pulmonary mucormycosis. Since corticosteroid use is a known risk factor for mucormycosis, the aim of this study was to describe the role of corticosteroids on AM capacities to control Lichtheimia corymbifera spore growth using a new ex vivo model. An in vivo mouse model was developed to determine the acetate cortisone dose able to trigger pulmonary invasive infection. Then, in the ex vivo model, male BALB/c mice were pretreated with the corticosteroid regimen triggering invasive infection, before AM collection through bronchoalveolar lavage. AMs from corticosteroid-treated mice and untreated control AMs were then exposed to L. corymbifera spores in vitro (ratio 1:5). AM control of fungal growth, adherence/phagocytosis, and oxidative burst were assessed using optical densities by spectrophotometer, flow cytometry, and 2', 7'-dichlorofluoresceine diacetate fluorescence, respectively. Cortisone acetate at 500 mg/kg, at D-3 and at D0, led to pulmonary invasive infection at D3. Co-incubated spores and AMs from corticosteroid-treated mice had significantly higher absorbance (fungal growth) than co-incubated spores and control AMs, at 24 h (P = .025), 36 h (P = .004), and 48 h (P = .001). Colocalization of spores with AMs from corticosteroid-treated mice was significantly lower than for control AMs (7.6 ± 1.9% vs 22.3 ± 5.8%; P = .003), reflecting spore adherence and phagocytosis inhibition. Finally, oxidative burst was significantly increased when control AMs were incubated with spores (P = 0.029), while corticosteroids hampered oxidative burst from treated AMs (P = 0.321). Corticosteroids enhanced fungal growth of L. corymbifera through AM phagocytosis inhibition and burst oxidative decrease in our ex vivo model. Lay Summary The aim of this study was to describe the impact of corticosteroids on alveolar macrophage (AM) capacities to control Mucorales growth in a new murine ex vivo model. Corticosteroids enhanced fungal growth of L. corymbifera through AM phagocytosis inhibition and burst oxidative decrease.

Nasal mucormycosis is a rare opportunistic infection of the nasal cavity and paranasal sinuses caused by saprophytic fungi which can rapidly lead to death. It usually affects individuals with poorly controlled diabetes mellitus (especially those with ketoacidosis), solid malignancies, iron overload, extensive burns, in patients undergoing treatment with glucocorticosteroid agents and in patients with neutropenia related to haematologic malignancies. Presentation of nasal mucormycosis is always very extensive, but in some patients, it can present in chronic indolent form also. Here, we present a case of 65-year old male with a history of exposed nasal bone after nasal trauma 8 months back. His diabetes was in control with oral hypoglycaemics. Debridement and local flap closure was done. Culture showed the growth of Lichtheimia corymbifera and in HPE, the fungus was seen branching at right angles. So, we conclude that the possibility of nasal mucormycosis should always be borne in mind so that early and effective treatment can be initiated on time to decrease the morbidity and mortality.

Watermelon peel waste (WPW) is being used for first time in single cell oils (SCOs) production via a promising oleaginous fungus Lichtheimia corymbifera which was isolated from Egyptian ecosystem. Pretreatments of WPW were carried out by mechanical, physical and chemical methods; the most potent pretreatment was selected according to total reducing sugar and total lipid production. Accordingly, the mechanical ptetreatment of WPW was distinctly the best pretreatment method for SCOs production from L. corymbifera. Taguchi design clarified that the most optimal culture conditions were 35 °C and pH 7.0 for 4 days by which the highest potential of SCOs and lipid content was yielded (2.93 gl−1 and 39.56% respectively). Mechanical treatment revealed that the dominant fatty acid was palmitic and oleic acids with 41.98 and 34.65% respectively with appearance of γ linolenic acid (GLA) at low concentration 1.43%. Finally, this study showed that WPW was used as a natural, effective, economic, ecofriendly and integrated substrate without adding any outsource nutrients to produce sustainable SCOs with low cost production.

Patient: Female, 6 Final Diagnosis: Acute lymphoblastic leukemia Symptoms: Abdominal pain • bloody diarrhea • malaise • vomiting Medication: — Clinical Procedure: Chemotherapy Specialty: Oncology Objective: Unusual clinical course Background: Malignant hypercalcemia is a rare finding in the pediatric population, even more rare in hematological malignancies, such as leukemia. Case Report: We present a case of a 6-year-old female patient who was diagnosed with acute lymphoblastic leukemia, with secondary hypercalcemia. She started chemotherapy following the IC-BFM ALL2002 protocol with simultaneous calcitonin, diuretics and aggressive hydration for hypercalcemia, and went into complete remission after the induction therapy. After 4 months of chemotherapy, she was diagnosed with relapse associated again with malignant hypercalcemia, and underwent chemotherapy with the relapse protocol. There was no response after the first 2 cycles, so we decided to start her on clofarabine. Due to the severe hypercalcemia and consecutive osteolysis, she developed several bone fractures and needed gypsum immobilization. We started her again on calcitonin, but she developed severe adverse reactions, so we found it necessary to start bisphosphonates, first zoledronic acid intravenously, and afterwards clodronate orally. Consolidation of bone fractures was achieved, but due to prolonged immobilization she developed bedsores, superinfected with Lichtheimia corymbifera. We started posaconazole orally, but she rapidly went into severe sepsis with multiple organ failure. The leukemia showed no response to chemotherapy, progressed rapidly, and the patient died. Conclusions: Malignant hypercalcemia is associated with a poor prognosis in leukemia, and might need a more aggressive therapy.

Objective. To assess the incidence rate, risk factors and treatment outcomes of mucormycosis in children with hematological malignancies in the large tertiary hematology/oncology center. Materials and Methods. A total of 16 children (9 males/7 females) with mucormycosis were enrolled in a single-center, retrospective study over the period of 2012–2018. All patients had an underlying diagnosis of acute leukemia. Mucormycosis was diagnosed at the different timepoints after chemotherapy (CT) or hematopoietic stem cell transplantation (HSCT) in 15 cases and before CT in 1 case. The diagnosis of mucormycosis was based on clinical, microbiological or histological results. The median patient’s age at the time of mucormycosis diagnosis was 7.7 years. Results. The average incidence of mucormycosis was 1.15%, while in 2018 the overall incidence was significantly increased to 4% (p = 0.039), primarily due to patients with acute myeloid leukemia (9.75%, р = 0.004). The main risk factors were prolonged neutropenia (median – 30 days)

Interlaboratory evaluations of Mucorales qPCR assays were developed to assess the reproducibility and performance of methods currently used. The participants comprised 12 laboratories from French university hospitals (nine of them participating in the Modimucor study) and 11 laboratories participating in the Fungal PCR Initiative. For panel 1, three sera were each spiked with DNA from three different species (Rhizomucor pusillus, Lichtheimia corymbifera, Rhizopus oryzae). For panel 2, six sera with three concentrations of R. pusillus and L. corymbifera (1, 10, and 100 genomes/ml) were prepared. Each panel included a blind negative-control serum. A form was distributed with each panel to collect results and required technical information, including DNA extraction method, sample volume used, DNA elution volume, qPCR method, qPCR template input volume, qPCR total reaction volume, qPCR platform, and qPCR reagents used. For panel 1, assessing 18 different protocols, qualitative results (positive or negative) were correct in 97% of cases (70/72). A very low interlaboratory variability in Cq values (SD = 1.89 cycles) were observed. For panel 2 assessing 26 different protocols, the detection rates were high (77–100%) for 5/6 of spiked serum. There was a significant association between the qPCR platform and performance. However, certain technical steps and optimal combinations of factors may also impact performance. The good reproducibility and performance demonstrated in this study support the use of Mucorales qPCR as part of the diagnostic strategy for mucormycosis.

Mucormycoses are invasive infections by Rhizopus species and other Mucorales. Over 10 months, four solid organ transplant (SOT) recipients at our centre developed mucormycosis due to Rhizopus microsporus (n=2), R. arrhizus (n=1) or Lichtheimia corymbifera (n=1), at a median 31.5 days (range: 13–34) post-admission. We performed whole genome sequencing (WGS) on 72 Mucorales isolates (45 R. arrhizus, 19 R. delemar, six R. microsporus, two Lichtheimia species) from these patients, from five patients with community-acquired mucormycosis, and from hospital and regional environments. Isolates were compared by core protein phylogeny and global genomic features, including genome size, guanine–cytosine percentages, shared protein families and paralogue expansions. Patient isolates fell into six core phylogenetic lineages (clades). Phylogenetic and genomic similarities of R. microsporus isolates recovered 7 months apart from two SOT recipients in adjoining hospitals suggested a potential common source exposure. However, isolates from other patients and environmental sites had unique genomes. Many isolates that were indistinguishable by core phylogeny were distinct by one or more global genomic comparisons. Certain clades were recovered throughout the study period, whereas others were found at particular time points. In conclusion, mucormycosis cases could not be genetically linked to a definitive environmental source. Comprehensive genomic analyses eliminated false associations between Mucorales isolates that would have been assigned using core phylogenetic or less extensive genomic comparisons. The genomic diversity of Mucorales mandates that multiple isolates from individual patients and environmental sites undergo WGS during epidemiological investigations. However, exhaustive surveillance of fungal populations in a hospital and surrounding community is probably infeasible.

Pulmonary mucormycosis are life-threatening invasive fungal infections affecting immunocompromised patients. First-line treatment is based on liposomal amphotericin B (AmB). Despite treatment, mortality remains high. The aim of this thesis was to optimize preventive and curative treatments of pulmonary mucormycosis. This thesis was divided in 2 axes, curative and preventive, themselves divided in two parts.The first aim of preventive axis was to study reactivation of mucormycosis. This concept was described in a first publication. Fungi can remain latent after an asymptomatic primary infection. After a latency period, they may be reactivated in the event of major immune deficiency leading to symptomatic infection. A mouse model was developed to reproduce this concept and assess AmB as decolonizing treatment. Decolonization using AmB was effective to prevent the disease.In the second part of this axis, the role of corticosteroids in infection pathophysiology was studied. An ex vivo model was developed to expose mouse alveolar macrophages to an infection-triggering dose of corticosteroids. In this model, corticosteroids were administered to naive mice, and then alveolar macrophages were collected by bronchoalveolar lavage. Alterations induced by corticosteroids on alveolar macrophages co-incubated with fungal spores were then studied in vitro. Corticosteroids decreased alveolar macrophage capacity to control fungal growth through phagocytosis and oxidative burst alterations.In the first part of curative axis, an acute pulmonary mucormycosis model was developed to study physiopathology of this infection. This model will be used to explore fungal-host-antifungal relationship.In the second part of this axis, in vitro combinations using AmB and several compounds were evaluated in order to improve AmB efficacy. These combinations were tested by checkerboard assays on several strains of Mucorales. After screening of 20 compounds (antibiotics, antifungal agents, terpene alcohols, surfactants), a candidate was identified, PEG15HS, which decreased AmB minimum inhibitory concentrations.; La mucormycose pulmonaire est une infection fongique invasive grave affectant les patients immunodéprimés. Le traitement de référence fait appel à l’amphotéricine B (AmB) liposomale mais reste peu efficace avec environ 50% de mortalité malgré celui-ci. Le but de cette thèse était d’optimiser le traitement préventif et curatif de la mucormycose pulmonaire. Pour cela, cette thèse a été structurée en 2 axes, un axe préventif puis un axe curatif, eux-mêmes divisés en deux sous-parties.La première partie de l’axe « préventif » s’intéressait au phénomène de réactivation des infections fongiques invasives. Ce concept a été décrit dans un premier article. Son postulat est le suivant : suite à une primo-infection asymptomatique, une seconde infection peut se produire à distance à la faveur d’une immunodépression. Un modèle murin a été développé pour reproduire ce concept et évaluer l’intérêt de l’AmB en décolonisation pour prévenir ce phénomène de réactivation. L’AmB en décolonisation s’est révélé efficace pour prévenir la survenue de la maladie.La seconde partie de cet axe avait pour but d’étudier le rôle des corticoïdes dans la physiopathologie de l’infection. Pour ce faire, un modèle ex vivo qui consiste à administrer des corticoïdes à des souris, puis à récupérer les cellules pulmonaires par lavage broncho-alvéolaire a été mis au point. Les perturbations induites par les corticoïdes sur les cellules immunitaires ont ensuite été étudiées in vitro. Les corticoïdes ont diminué la capacité globale des macrophages alvéolaires à inhiber la filamentation du champignon, diminué la capacité de phagocytose des macrophages alvéolaires et leur capacité de « killing » oxydatif.La première partie de l’axe « curatif » a consisté à développer un modèle murin de mucormycose pulmonaire aigüe afin d’étudier la physiopathologie de cette infection. Ce modèle a été caractérisé sur les plans histologiques et immunitaires et permettra d’explorer la relation champignon-hôte-antifongique. La seconde partie de cet axe a permis d’évaluer in vitro des associations entre AmB et diverses molécules afin d’améliorer l’efficacité de l’AmB. Ces combinaisons ont été testées par technique de chequerboard sur différentes souches de Mucorales. Après avoir passé au crible 20 candidats (antibiotiques, antifongiques, alcools terpéniques, tensioactifs), un a été identifié, le PEG15HS, qui permet de diminuer les concentrations minimales inhibitrices d’AmB

Mucormycosis is an emergent, fatal fungal infection of humans and warm-blooded animals caused by species of the order Mucorales. Immune cells of the innate immune system serve as the first line of defence against inhaled spores. Alveolar macrophages were challenged with the mucoralean fungus Lichtheimia corymbifera and subjected to biotinylation and streptavidin enrichment procedures followed by LC-MS/MS analyses. A total of 28 host proteins enriched for binding to macrophage-L. corymbifera interaction. Among those, the HSP70-family protein Hspa8 was found to be predominantly responsive to living and heat-killed spores of a virulent and an attenuated strain of L. corymbifera. Confocal scanning laser microscopy of infected macrophages revealed colocalization of Hspa8 with phagocytosed spores of L. corymbifera. The amount of detectable Hspa8 was dependent on the multiplicity of infection. Incubation of alveolar macrophages with an anti-Hspa8 antibody prior to infection reduced their capability to phagocytose spores of L. corymbifera. In contrast, anti-Hspa8 antibodies did not abrogate the phagocytosis of Aspergillus fumigatus conidia by macrophages. These results suggest an important contribution of the heat-shock family protein Hspa8 in the recognition of spores of the mucoralean fungus L. corymbifera by host alveolar macrophages and define a potential immunomodulatory therapeutic target.

Pathogenic mucormycetes induce diseases with considerable morbidity and mortality in immunocompromised patients. Virulence data comparing different Mucorales species and various underlying risk factors are limited. We therefore compared the pathogenesis of inhalative infection by Rhizopus (R.) arrhizus and Lichtheimia (L.) corymbifera in murine models for predominant risk factors for onset of infection. Mice with diabetes or treated with cyclophosphamide or cortisone acetate were challenged via the intranasal route with an isolate of R. arrhizus or L. corymbifera, respectively. Clinical, immunological and inflammation parameters as well as efficacy of posaconazole prophylaxis were monitored over 14 days. Whereas immunocompetent mice showed no clinical symptoms after mucormycete infection, mice treated with either cyclophosphamide (CP) or cortisone acetate (CA) were highly susceptible. Animals infected with the isolate of R. arrhizus showed prolonged survival and lower mortality, compared to those exposed to the L. corymbifera isolate. This lower virulence of R. arrhizus was risk factor-dependent, since diabetic mice died only after infection with Rhizopus, whereas all Lichtheimia-infected diabetic animals survived. Under posaconazole prophylaxis, both mucormycetes were able to establish breakthrough infections in CA- and CP-treated mice, but the course of infection was significantly delayed. Detailed analysis revealed that susceptibility of CA- and CP-treated mice could not be mimicked by exclusive lack or downmodulation of neutrophils, platelets or complement, but can be supposed to be the consequence of a broad immunosuppressive effect induced by the drugs. Both Lichtheimia corymbifera and Rhizopus arrhizus induce invasive mycoses in immunocompromised hosts after inhalative infection. Key parameters such as virulence and immunopathogenesis vary strongly according to fungal species and underlying risk group. Selected neutropenia is no sufficient risk factor for onset of inhalative mucormycosis.

В сканирующем электронном микроскопе (СЭМ) изучали особенности микро-морфологии культур Lichtheimia corymbifera (Cohn) Vuill (РКПГF-1601/1966) и Rhizopus arrhizus A. Fisch. (РКПГF-1537), выращенных на среде Сабуро. Для культур L. corymbifera характерно умеренно выраженное асинхронное спороношение. Для зрелых клеток вегетативного мицелия, спорангиеносцев, спорангиев и спорангиоспор этого вида свойственно наличие мелкозернистой скульптуры поверхности. Для колоний R. arrhizus характерно обильное спороношение. Выявлено, что поверхность клеточных стенок спорангиеносцев молодых спорангиев и клеток вегетативного мицелия данного вида гладкая, тогда как с возрастом она становится поперечно-складчатой. Показано, что формирование элементов слоя орнаментации спорангиоспор обоих видов происходит асинхронно после их освобождения из спорангия., In scanning electron microscopes (SEM) micro-morphological peculiarities of the Lichtheimia corymbifera (Cohn) Vuill (РКПГF-1601/1966) and Rhizopus arrhizus A. Fisch. (РКПГF-1537) cultures grown on Sabouraud medium were studied. For cultures of L. corymbifera was typical moderately asynchronous sporulation. For the mature cells of vegetative mycelium, stipes of the sporangies, sporangia and sporangiospores of this species were typical the presence of fine-grained surface sculpture. Colonies R. arrhizus were characterized by abundant sporulation. It was revealed that the surface of the cell walls of the stipes of young sporangia and cells of vegetative mycelium of this species were smooth, while with age it becomes transversely folded. It is shown that the formation of elements of the sporangiospores ornamentation layer in both species takes place asynchronous after their release from sporangium.

Background Invasive mucormycosis is a very aggressive fungal disease among immunocompromised pediatric patients caused by saprophytic fungi that belong to the order of the Mucorales. Case Report We describe a case of of Lichtheimia corymbifera infection in a 15-year-old child with B-cell Non-Hodgkin Lymphoma (NHL) involving lung, kidney and thyroid that initially was diagnosed as probable aspergillosis delaying the effective therapy for mucormycosis. Conclusions This case showed that also intensive chemotherapy with rituximab may represent a risk factor for mucormycosis infection. Liposomal amphotericin B and surgery remain key tools for a successful treatment of this aggressive disease.

Contains fulltext : 229601.pdf (Publisher’s version ) (Closed access) BACKGROUND: Lichtheimia species are emerging opportunistic fungal pathogens in the Mucorales, causing serious skin and respiratory infections in immunocompromised patients. Established agents are Lichtheimia corymbifera and L. ramosa, while L. ornata is a novel agent. Available data on a species-specific analysis of Lichtheimia infections are limited. METHODS: The first case of a fatal rhino-orbital-cerebral infection in a hematopoietic stem cell transplantation recipient caused by L. ornata is reported; the agent was identified by sequencing the ITS ribosomal region. We reviewed the literature on mucormycosis due to Lichtheimia species between 2009 and 2018, with an analysis of risk factors and epidemiological and clinical data. RESULTS: In addition to our Lichtheimia ornata case, 44 cases of human Lichtheimia were analyzed. Lichtheimia predominated in Europe (68.2%), followed by Asia (16%), and Africa (9%). The most common underlying condition was hematological malignancy (36.3%), followed by trauma/major surgery (27.3%), while diabetes mellitus was rare (11.4%). Site of infection was mostly skin and soft tissues (45.5%) and lung (25%), while relatively few cases were disseminated (13.6%) or rhinocerebral (11.4%). Mortality (36.4%) was mainly due to disseminated and rhinocerebral infections. CONCLUSION: In contrast to Rhizopus, the most common agent of mucormycosis recorded in patients with diabetes mellitus, Lichtheimia infections were primarily associated with hematological malignancies and major skin barrier damage. Given the fact that classical rhinocerebral mucormycosis remains difficult to treat, independent of causative species, timely application of amphotericin B accessory to debridement may be required for patient survival.

В сообщении представлены морфологические свойства двух модельных мукоромицетов − Rhizopus oryzae РКПГ F-1537 и Lichtheimia corymbifera РКПГ F-1601, которые применяют в опытах по воспроизведению мукормикоза на лабораторных животных. Оба штамма прошли процедуру экспертной видовой идентификации методом таргетного ДНК-секвенирования по региону внутреннего транскрибируемого спейсера (ITS) и D1/D2-домену рибосомальной РНК большой субъединицы. Результаты исследования включают описания макрои микроморфологического строения культур избранных штаммов, где особое внимание уделено наблюдению интактных посевов в проходящем свете, в том числе с помощью стереомикроскопа. У L. corymbifera более подробно, нежели это отражено в современных атласах и руководствах, определили варианты строения субстратного мицелия, видоизменения ризоидов, а также формы ветвления спорангиеносцев. Наблюдаемый штамм R. oryzae проявил морфологические свойства, характерные для вида. В статье также представлены краткие сведения об истории изучения морфологии и идентификации этих двух видов и группы мукоромицетов в целом., In the present communication the authors described the morphological properties of two model mucoromycetes − Rhizopus oryzae RCPF F-1537 and Lichtheimia corymbifera RCPF F-1601, which are used in experiments for the reproduction of mucormycosis in laboratory animals. Both strains were passed the procedure of expert species identification by targeted DNA sequencing of internal transcribed spacer (ITS) and the D1/D2 domain of large subunit ribosomal RNA. The results of the study include descriptions of the macroand micromorphological structure of cultures of selected strains, where special attention is paid to the observation of intact passages in transmitted light, including stereomicroscopy. In L. corymbifera, in more details than are reflected in modern atlases and manuals, we determined the structure of the substrate mycelium, the modification of rhizoids, as well as the branching forms of sporangiophores. The observed R. oryzae strain exhibited morphological properties characteristic of the species. The article although provides brief information about the history of the study of morphology and the identification of these two species and the group of mucoromycetes in general, including domestic and foreign sources.

C 2002 по 2020 гг. в регистр проспективно включили 83 взрослых больных «доказанным» и «вероятным» мукормикозом (EORTC/MSGERC, 2019). Наиболее частыми фоновыми заболеваниями мукормикоза были онкогематологические заболевания (67%). Возбудители мукормикоза: Rhizopus spp. (28%), Lichtheimia corуmbifera (22%), Mucor spp. (18%), Rhizomucor pusillus (12%), Rhizomucor spp. (8%), Rhizopus microsporus (6%), Rhizopus arrhizus (2%), Rhizomucor variabilis (2%), Rhizopus stoloniter (2%). Поражение легких выявили у 65% пациентов. Антимикотическую терапию применяли у 76% больных, хирургическое лечение - у 52%. Общая выживаемость пациентов в течение 12 недель составила 63%., In 2002-2020 years in prospective study were included 83 adult patients with «proven» and «probable» mucormycosis (EORTC/MSGERC, 2019). The most frequent underlying conditions were hematological diseases (67%). The etiology agents were: Rhizopus spp. (28%), Lichtheimia corуmbifera (22%), Mucor spp. (18%), Rhizomucor pusillus (12%), Rhizomucor spp. (8%), Rhizopus microsporus (6%), Rhizopus arrhizus (2%), Rhizopus oryzae (2%), Rhizopus stoloniter (2%). Pulmonary mucormycosis was main clinical form in 65% of patients. Antifungal therapy was used in 76% patients, surgery - 52%. 12 weeks overall survival was 63%.

A 7-month-old female Japanese Black calf developed elongated, nodular mass measuring 30 × 16 cm extended from the retropharyngeal region to mid lateral neck region. Histological examination revealed granulomatous lymphangitis with non-septate fungal hyphae recognized throughout the lesions. Fungal culture, DNA sequencing and molecular phylogenetic tree analysis confirmed the sequence of Lichtheimia corymbifera. The lymphogenous route was speculated to be the main route of fungal spread leading to the characteristic nodular appearance of this case. Keywords: Bovine, Lichtheimia corymbifera, Lymphogenous route, Mucormycosis