Mucor Research Articles

Epidemiological Trends of Mucormycosis in Europe, Comparison with Other Continents.

Mucormycosis is an invasive fungal infection, caused by fungi of the order Mucorales, and it is associated with high morbidity and mortality. The epidemiology of mucormycosis is evolving. The incidence, underlying risk factors, clinical presentation, as well as the responsible mucoralean agents, vary by geographic region. The estimated incidence in developed countries ranges from less than 0.06 to 0.3 cases per 100,000 population per year, while in India, it reaches approximately 14 cases per 100,000 population per year, which is about 80 times higher. In European countries the estimated incidence ranges from less than 0.04 to 0.12 per 100,000 population per year. Diabetes mellitus (DM) is the leading underlying disease globally. In Europe, hematological malignancies are the most common risk factor for mucormycosis, while in Asia diabetes predominates. The rhino-cerebral form of mucormycosis is most commonly seen in patients with DM, whereas pulmonary mucormycosis in patients with hematological malignancies and transplants. The most common species globally is Rhizopus arrhizus, whereas new emerging species only occasionally cause infection in Europe. However, vigilance is required, as they may raise concerns-especially in light of climate change- due to their potential to cause serious infections in both immunocompetent and immunosuppressed individuals.

Orbital apex syndrome in a man with rhino-ocular cerebral mucormycosis: a case report

BackgroundOrbital apex syndrome is a symptom complex of visual loss and ophthalmoplegia resulting from a disease involving the orbital apex. It can be caused by inflammation, infection, and malignancies. Mucormycosis is an infection caused by filamentous saprophytes of the order Mucorales. It is ubiquitous, and the infection can occur from ingesting contaminated food, inhaling spores, or injecting the disrupted skin or wounds. It is mainly a disease of the immunocompromised, affecting patients with poorly controlled diabetes, organ transplant recipients, and patients with hematological malignancies. We present the case of a man with orbital apex syndrome resulting from rapidly spreading rhino-ocular cerebral mucormycosis, who had a poor outcome despite an aggressive combined medical and surgical treatment. This is an unusual cause of orbital apex syndrome.Case presentationA 46-year-old Bangladeshi man presented to the emergency department with a history of toothache and pain in the left eye. On examination, the patient had a left-sided periorbital edema, ptosis, and proptosis. He had complete ophthalmoplegia and absent direct pupillary response in the left eye. Magnetic resonance imaging of the brain and orbit showed bilateral ethmoidal, left frontal, maxillary, and sphenoidal sinusitis with left orbital cellulitis. His left orbit was surgically decompressed and histology confirmed mucormycosis. Despite aggressive treatment, the patient had only a partial improvement in his symptoms.ConclusionsMucormycosis is a rare disease that can easily be misdiagnosed, leading to delayed treatment and disease dissemination. Clinicians must be suspicious of mucormycosis in patients presenting with multiple cranial nerve palsy.

Venous intestinal ischemia of fungal origin as a cause of intestinal obstruction in immunocompromised patients: case report and literature review

BackgroundMucormycosis is a highly lethal opportunistic fungal disease caused by ubiquitous molds of the order Mucorales, with Rhizopus, Lichtheimia and Mucor being the most common genera. This rare disease primarily affects immunocompromised patients, with presentations ranging from rhino-orbito-cerebral infections to disseminated mucormycosis with angioinvasion, leading to thrombosis and tissue infarction. Gastrointestinal mucormycosis is the least common clinical presentation and is believed to be secondary to spore ingestion. It can involve multiple components of the gastrointestinal tract, such as the stomach, liver, ileum, and colon, with nonspecific manifestations, including pain, nausea, vomiting, and abdominal distension. The initial clinical presentation may even manifest as gastrointestinal bleeding due to gastric ulceration or intestinal perforation.Case presentationHere we present the case of a 48-year-old male patient with a 9-year history of human immunodeficiency virus (HIV) infection who was hospitalized in the context of febrile neutropenia and whose acute respiratory infection was documented; therefore, antibiotic treatment was initiated. However, due to persistent febrile peaks and peripheral blood showing documentation of multilineage cytopenias, a bone marrow biopsy was performed, compatible with presenting features of marrow myelodysplasia. During hospitalization, the patient presented left flank abdominal pain, and an abdominal computed tomography (CT) scan revealed signs of intussusception of a small bowel loop at the distal jejunum level, leading to intestinal obstruction with ischemic progression, requiring ileectomy (60 cm). Histopathological analysis of the resected intestine revealed severe transmural ischemic changes associated with venous thrombosis due to fungal structures, with histochemical studies demonstrating the presence of zygomycete (Mucor) fungal structures, leading to the initiation of treatment with amphotericin B. However, despite treatment, the patient experienced progressive clinical deterioration with persistent fever and ventilatory failure, with follow-up tests showing absolute neutropenia and blood cultures positive for yeast, leading to death 52 days after admission.ConclusionsThe diagnosis of intestinal mucormycosis may be delayed due to the lack of specificity of the signs and symptoms. Pathologists as well as histopathological studies are essential for timely treatment.

Recent Advances in Diagnostic Approaches for Mucormycosis.

Mucormycosis, an invasive fungal infection caused by members of the order Mucorales, often progresses fulminantly if not recognized in a timely manner. This comprehensive review discusses the latest developments in diagnostic approaches for mucormycosis, from traditional histopathology and culture-based methods to advanced and emerging techniques such as molecular assays, imaging, serology, and metabolomics. We discuss challenges in the diagnosis of mucormycosis and emphasize the importance of rapid and accurate identification of this life-threatening infection.

Clinical Test Comparison for Improved Diagnosis of Mucormycosis

Abstract Mucormycosis is a rapidly progressive and invasive fungal infection caused by members of the order Mucorales. Proper treatment relies on a timely diagnosis. However, traditional fungal culture takes several days to weeks and has low sensitivity for recovering Mucorales, as these organisms are sensitive to specimen preparation, including tissue homogenization, and low storage temperatures. More rapid and sensitive diagnostic methods are needed to promptly detect infection. Our laboratory previously developed a real-time PCR assay that detects the most common genera associated with mucormycosis to help improve diagnosis. The assay was analytically validated for a variety of specimen types including serum, tissue (both fresh and FFPE), respiratory secretions and body fluids. Little is known about the agreement between our laboratory developed PCR and other detection methods such as culture or sequencing. We reviewed 6 years of laboratory data to assess overall PCR positivity rate, positivity rate across sample types, and agreement with culture and/or pan-fungal sequencing. We also calculated turnaround time to results to gauge the diagnostic value of Mucorales PCR. Test comparisons with fungal culture and/or pan-fungal sequencing were performed if testing was ordered within 30 days of each other. In our study, we reviewed 3,804 total PCR orders for 2,195 patients. The overall positivity rate of Mucorales PCR orders was 3.81% and varied among different sample types, with fresh tissue and body fluid having the highest positivity rates (18.11% total tissue (33.3% lung tissue) and 10.94% all body fluid (12.5% pleural fluid)) and sputum and CSF having the lowest positivity rates (<1% positivity for both). In a cohort of 428 patients with fungal culture and/or sequencing also performed, 29 patients tested positive for Mucorales by at least one method. PCR detected Mucorales on average 7.83 days sooner than fungal culture (average time to positive result: 3.65 vs. 11.47 days). In patients with culture- or sequencing-confirmed Mucorales infection, PCR had a 100% agreement when comparing shared samples from the same source and collection time. Mucorales PCR was also able to detect infection in 10 (34.5%) other patients who were culture-negative for Mucorales. Our findings suggest that PCR could be a valuable diagnostic tool for suspected mucormycosis, especially tissue invasive disease. PCR increased case detection by 34.5% with a faster turnaround time than culture with lesser cost than sequencing. The main limitation of our study was lack of access to patient information to assess pretest probability of Mucormycosis.

Angioinvasive Rhino-Orbital-Cerebral Mucormycosis in a Patient with Type 2 Diabetes Mellitus: A Complex and Lethal Cause of Stroke

Rhino-orbital-cerebral mucormycosis is a rapidly progressive and often fatal fungal infection caused by molds of the order Mucorales, particularly affecting immunocompromised individuals. This infection is notorious for its angioinvasive properties, enabling the fungi to invade blood vessels and leading to tissue necrosis. We report the clinical course of a 59-year-old Caucasian man with poorly controlled type 2 diabetes (HbA1c 16.8%) who presented with unilateral headache, left-sided facial numbness, and incomplete left ocular motor paresis. Initial presentation raised suspicion of orbital phlegmon, leading to antibiotic and later corticosteroid pulse therapy, which worsened the patient’s condition. Subsequent imaging demonstrated extensive inflammatory changes, including wall irregularities of the left intracranial internal carotid artery, accompanied by ocular protrusion and periorbital enhancement. New palatal lesions indicated mucormycosis, which was confirmed by molecular analysis of a palatal biopsy, leading to Amphotericin B treatment. Pre-surgery imaging revealed a malignant middle cerebral artery infarction, and the patient died 16 days after symptom onset and 12 days after initial presentation under palliative care due to a poor prognosis. This case of angioinvasive mucormycosis underscores the severe and often fatal course of rhino-orbital-cerebral mucormycosis in an immunocompromised individual. The rapid progression from initially vague and unspecific symptoms to extensive vascular involvement and stroke highlights the critical need for early and accurate diagnosis, as well as prompt intervention to prevent further disease progression. Additionally, this case also illustrates the potential risks associated with corticosteroid therapy in the presence of undiagnosed fungal infections, which can exacerbate the condition and lead to serious complications. Clinicians should maintain a high index of suspicion for mucormycosis in similar clinical scenarios, prioritizing adequate antifungal treatment and careful monitoring to improve patient outcomes. Early interdisciplinary collaboration is essential for the effective management of such complex cases.

A-273 Rapid, Portable Invasive Fungal Infection Diagnostic and Candida Antimicrobial Susceptibility Testing

Abstract Background Traumatic wounds are associated with a higher risk of invasive fungal infections (IFI), which lead to a significant increase in amputation or death. Actionable treatment decisions are hampered because true infections can be difficult to differentiate from external wound contaminates, and tissue biopsy and quantification of fungal load is required to determine if treatment is necessary, which currently takes several days. GeneCapture is developing the CAPTURE 60-minute, portable infection identification platform to detect infectious levels of common fungi including the genera Aspergillus, Fusarium, and Scedosporium, the family Herpotrichiellaceae, and the order Mucorales. The company is also pursuing rapid identification and antimicrobial susceptibility testing for Candida species from multiple infection types. Methods This study seeks to determine the Limit of Detection (LoD), sensitivity and specificity of the CAPTURE ID assay for fungal pathogens. Since tissue biopsy samples must be used to assess the presence of IFI in wounds, GeneCapture has developed a manual process for the crude homogenization of muscle tissue to allow this matrix to be used as the starting sample for the ID assay. Mock samples were tested for inclusivity and exclusivity on a series of IFI ID panels against multiple strains of the included fungi, against fungi not yet specifically detected on the panel, and against bacteria that commonly infect wounds. While the LoD for yeasts may be determined in CFU/mL, there is no similar, easy-to-define metric for molds. GeneCapture has developed a quantitative PCR method to detect the single copy beta-tubulin gene to roughly correlate fungal dry mass and nuclei number to assay signal for molds cultured in Potato Dextrose Broth. Determining beta-tubulin copy numbers for extracts from mock samples then allowed detection of the progression of IFI over the course of infection. Lastly, antimicrobial susceptibility testing (AST) was performed on two species of Candida to validate utilizing GeneCapture’s rapid phenotypic AST method for fungal infections. Results To date, the CAPTURE ID panel has been tested against 27 included or excluded strains of fungi or bacteria with 97% sensitivity and 100% specificity. The current LoD for mold organisms varies from approximately 1,000 nuclei for Aspergillus species, to 100,000 nuclei for Fusarium species. Additional work to understand this range is underway. Lastly, we have correctly determined the susceptibility of Candida species using our novel approach within 4-6 hours. Conclusions GeneCapture’s ID and AST technology offer a unique solution to address the increasing prevalence of fungal infections. Our platform can identify the most common fungal components in a wound within 60 minutes of receiving a tissue biopsy sample. Candida infections occur across multiple matrices and rapidly identifying the species of Candida and then determining its phenotypic susceptibility profile will have a large impact on treating these difficult pathogens.

Soil-Inhabiting microscopic fungi of the foothill forests of Bu Gia Map National Park (Vietnam)

The information about species composition and conformation characteristics of microfungi’s complexes in the soil and leaf litter of specially protected natural areas of Vietnam. The mycological examinations of the Bu Zia Map National Park were carried out for the first time. List of species that was found by dilution plate method from 60 samples includes 88 species of microscopic fungi belonging to 42 genera and 15 types of sterile forms. 13 species of them were not observed previously for Vietnam. Mucoromycota was represented by only two species that related to the order Mucorales. Basisiomycota was represented by only one species. The most of identified fungi belongs to Ascomycota, domitant part of them is anamorphic. The leading orders are Eurotiales (42 species) and Hypocreales (17 species). Among the anamorphic forms there is a lot of different species Aspergillus and Penicillium. In soil from dipterocarp forest were identified 36 species microscopic fungi from 19 genera and eight sterile forms were isolated. There are three species were included in the group of dominants: Aspergillus tubingensis, Penicillium ochrochloron, Trichoderma harzianum. On a forest with Lagerstroemia sp. (Lythraceae) was found 47 species from 24 genera and 4 sterile forms were isolated. In the palm tropical forest area with Arenga westerhoutii (Arecaceae) 44 species of micromycetes from 27 genera and 5 sterile forms were isolated. The number of typical (dominant and frequent) species is very large, especially for the complex of micromycetes of the soil. Purpureocillium lilacinum and Trichoderma harzianum were also present. Rare tropical fungi have been found, such as Heterocephalum taiense, Chaetomella circinoseta and C. raphigera – soil fungi that are usually isolated from tropical soils and plants. Endocalyx melanoxanthus that has a tropical distribution and is associated with palm trees was found in Vietnam for the first time. The micromycete Thielaviopsis radicicola which is a rather serious pathogen of palm was found in the soil in a forest area with a predominance of Lagerstroemia sp. Complexes of micromycetes of the studied forest areas are divided into groups according to the types of habitats studied and by the types of different substrates. The complexes of micromycetes that were found in the soil and on the litter of the Lagerstroemia forest are very different. The degree of study of the species composition for all habitats is not very high: from 56 to 78%. Further studies of this group are promising and may lead to the identification of new species.

Diagnostic Challenges of Mucormycosis in a Patient with Diabetes: A Case Report

Mucormycosis is a rare and life-threatening fungal infection that predominantly affects immunocompromised individuals, particularly those with poorly controlled diabetes mellitus. Achieving an accurate diagnosis remains a significant challenge in clinical practice. We report a case of mucormycosis in a 25-year-old woman who presented with an altered mental status and a 5 × 2 cm necrotic lesion on the left nasal septum, characterized by indistinct borders, during admission. Prolonged diagnostic investigations ultimately led to the identification of nasal mucormycosis attributable to Rhizomucor pusillus, a rare species within the Mucorales order, which complicates the diagnostic process. Unfortunately, the patient's clinical condition rapidly deteriorated, resulting in her demise prior to the administration of systemic antifungal therapy. Although the comprehensive evaluations facilitated the identification of the causative agent, the time required for this process did not favor the patient's prognosis. The atypical symptoms, swift progression, and infrequent occurrence of mucormycosis underscore the critical importance of its timely and accurate diagnosis to ensure favorable patient outcomes. Proper identification of the pathogen and immediate administration of therapeutic interventions can considerably enhance the likelihood of patient recovery and survival.

New lineages of RNA viruses from clinical isolates of Rhizopus microsporus revealed by fragmented and primer-ligated dsRNA sequencing (FLDS) analysis.

Rhizopus microsporus is a species in the order Mucorales that is known to cause mucormycosis, but it is poorly understood as a host of viruses. Here, we examined 25 clinical strains of R. microsporus for viral infection with a conventional double-stranded RNA (dsRNA) assay using agarose gel electrophoresis (AGE) and the recently established fragmented and primer-ligated dsRNA sequencing (FLDS) protocol. By AGE, five virus-infected strains were detected. Then, full-length genomic sequences of 12 novel RNA viruses were revealed by FLDS, which were related to the families Mitoviridae, Narnaviridae, and Endornaviridae, ill-defined groups of single-stranded RNA (ssRNA) viruses with similarity to the established families Virgaviridae and Phasmaviridae, and the proposed family "Ambiguiviridae." All the characterized viruses, except a potential phasmavirid with a negative-sense RNA genome, had positive-sense RNA genomes. One virus belonged to a previously established species within the family Mitoviridae, whereas the other 11 viruses represented new species or even new genera. These results show that the fungal pathogen R. microsporus harbors diverse RNA viruses and extend our understanding of the diversity of RNA viruses in the fungal order Mucorales, division Mucoromycota. Identifying RNA viruses from clinical isolates of R. microsporus may expand the repertoire of natural therapeutic agents for mucormycosis in the future.IMPORTANCEThe diversity of mycoviruses in fungal hosts in the division Mucoromycota has been underestimated, mainly within the species Rhizopus microsporus. Only five positive-sense RNA genomes had previously been discovered in this species. Because current sequencing methods poorly complete the termini of genomes, we used fragmented and primer-ligated double-stranded RNA sequencing to acquire the full-length genomes. Eleven novel mycoviruses were detected in this study, including the first negative-sense RNA genome reported in R. microsporus. Our findings extend the understanding of the viral diversity in clinical strains of Mucoromycota, may provide insights into the pathogenesis and ecology of this fungus, and may offer therapeutic options.

A global perspective of the changing epidemiology of invasive fungal disease and real-world experience with the use of isavuconazole.

Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.

Characterisation of the spatio-temporal localisation of a pan-Mucorales specific antigen during germination and immunohistochemistry.

Mucormycosis is an aggressive, invasive fungal infection caused by moulds in the order Mucorales. Early diagnosis is key to improving patient prognosis, yet relies on insensitive culture or non-specific histopathology. A pan-Mucorales specific monoclonal antibody (mAb), TG11, was recently developed. Here, we investigate the spatio-temporal localisation of the antigen and specificity of the mAb for immunohistochemistry. We use immunofluorescence (IF) microscopy to assess antigen localisation in eleven Mucorales species of clinical importance and live imaging of Rhizopus arrhizus germination. Immunogold transmission electron microscopy (immunoTEM) reveals the sub-cellular location of mAb TG11 binding. Finally, we perform immunohistochemistry of R. arrhizus in an ex vivo murine lung infection model alongside lung infection by Aspergillus fumigatus. IF revealed TG11 antigen production at the emerging hyphal tip and along the length of growing hyphae in all Mucorales except Sakasenea. Timelapse imaging revealed early antigen exposure during spore germination and along the growing hypha. ImmunoTEM confirmed mAb TG11 binding to the hyphal cell wall only. The TG11 mAb specifically stained Mucorales but not Aspergillus hyphae in infected murine lung tissue. TG11 detects early hyphal growth and has valuable potential for diagnosing mucormycosis by enhancing discriminatory detection of Mucorales in tissue.

Mucormycosis: An infection caused by a black fungus

The filamentous fungus that causes Mucormycosis is a newly discovered angiogenic infection that is found in large quantities and is a member of the Zygomycete class's Mucorales order. In patients undergoing hematopoietic and allogeneic stem cell transplantation, after candidiasis and aspergillosis, mucormycosis has become the third most common invasive mycosis. Breathing in sporangiospores is a daily need. The remarkably low frequency of Mucorales members in nasal mucus indicates that airborne contamination is either minimal or mucociliary transport removes spores from airway mucus. In this review research, new approaches to assessing the relationships among the host, the fungus, and antifungal drugs are provided. Aerosols and other novel delivery methods might also aid in the treatment of mucormycosis.

The underlying factors of occurrence of Mucormycosis in post-COVID-19 patients – A meta-analysis of case histories

Mucormycosis is a life-threatening fungal infection caused by fungi of the order Mucorales. It usually affects people with weakened immune systems, such as those with uncontrolled diabetes, acquired immunodeficiency syndrome, iatrogenic immunosuppression, and hematological malignancies, as well as individuals who have had organ transplants. The type of mucormycosis a person suffers from is often determined by their underlying conditions. The most common types are rhino-cerebral mucormycosis, pulmonary mucormycosis, cutaneous mucormycosis, cerebral mucormycosis, gastrointestinal mucormycosis, and disseminated mucormycosis. The incidence of mucormycosis has been increasing over the years, with an overall mortality rate of 54%. Recent cases have shown a correlation between COVID-19 and mucormycosis. Using anti-inflammatory drugs to combat the cytokine storm associated with COVID-19 can weaken the immune system, making individuals more susceptible to opportunistic fungal infections like mucormycosis. Underlying health conditions further exacerbate the condition. This study reviewing 198 cases of mucormycosis and conducting a meta-analysis found that post-COVID-19 patients most commonly developed rhino-orbital-cerebral mucormycosis, followed by pulmonary and gastrointestinal mucormycosis. The study also identified diabetes as the most common underlying factor contributing to the development of mucormycosis in post-COVID-19 patients, followed by hypertension and obesity. The study also examined the influence of age, affected organs, and the use of certain drugs on the development of mucormycosis. Age was found to be a significant factor in the infection. This meta-analysis is one of the first to compare post-COVID mucormycosis cases with those from the pre-COVID era. The hope is that this study and analysis will help identify the determinants of mucormycosis in post-COVID patients and aid the scientific community in finding a solution to this problem.

Myo5B plays a significant role in the hyphal growth and virulence of the human pathogenic fungus Mucor lusitanicus.

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.

Construction of the RNAi plasmids to suppress the expression of chitin synthase-encoding genes (<i>chs</i>) in fungus <i>Mucor lusitanicus</i>

Mucormycosis is an emerging fungal infection caused by many species belonging to the order Mucorales. The lack of effective therapies to treat this disease is due to our limited understanding of its pathogenesis. Chitin is one of the fungal-specific components of the cell wall. In fungi, chitin synthase and chitin deacetylase are the key enzymes involved in chitin biogenesis. The RNAi mechanisms have been well-studied in the fungus Mucor-lusitanicus, a model organism for mucormycosis studies. The RNAi technique has been previously applied to study gene function. In this study, two chitin synthase-encoding genes (chs1 and chs2) were identified using transcriptomic data. Approximately 1 kb of DNA fragments of the target genes were amplified and cloned into the pMAT1812 vector to generate the corresponding RNAi plasmids. Initial screening by colony PCR identified 3/10 and 1/10 potential colonies that might contain the RNAi plasmids. One plasmid for each clone was selected and named pAT63 and pAT64, corresponding to the chs1 and chs2 genes, respectively. The validation of these recombinant RNAi plasmids using different restriction enzymes (NotI - PvuII and SalI - PstI for plasmids pAT63 and pAT64, respectively) showed the expected results. The DNA sequencing of the plasmids pAT63 and pAT64 using specific primers validated the results of the screening process. These RNAi plasmids can be used to suppress the expression of the target genes. The silencing mechanism of the target genes will be triggered by the expression of the RNAi plasmids. This approach allows us to study the function of the chitin synthase-encoding genes in this fungus.

Mucormycosis in Diabetes

Abstract Fungal infections are a major health challenge especially in immunocompromised patients. Mucormycosis, a severe, frequently fatal fungal infection, has a unique predisposition to infect patients with diabetes. The infection is caused by organisms belonging to the order Mucorales, among which Rhizopus species are the most common. Uncontrolled diabetes complicated by diabetic ketoacidosis is one of the major risk factors for upsurge in mucormycosis cases. The defense mechanisms, involving macrophages and neutrophils for phagocytosis, are compromised in diabetes. In 2 cases of rhino-orbital-cerebral mucormycosis with underlying diabetes, we observed a marked immune imbalance, with elevated Th17 and diminished T regulatory cells. Recovery of CD4+CD25+ T cells after treatment indicated a favorable phenotype outcome; though high circulating CD4+CD161+ can be detrimental to the patient predisposing to future relapse(s). Mucorale specific T cells contributing to human immune responses against the fungi can be investigated to identify a surrogate diagnostic marker of invasive mucormycosis.

Fungal Infection in Upper Gastrointestinal Tract

Mycoses refer to infectious diseases caused by fungi. Fungal infections are rare and mainly occur as opportunistic infections in immunocompromised patients. Candida species are the most common cause of mycosis; however, members of the order Mucorales or genus <i>Aspergillus</i> may also cause serious fungal infections in immunocompromised hosts. Fungal infections of the gastrointestinal (GI) tract can be asymptomatic or may present with abdominal pain, bloating, diarrhea, or GI bleeding. Although rare, thorough understanding of fungal infections of the upper GI tract encountered in real-world clinical settings can enable early diagnosis and prompt initiation of treatment to improve patient prognosis.

Mucormycosis: A sweet enemy, case series

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.

An Atypical Presentation of Pulmonary Mucormycosis

Abstract Mucormycosis is a life-threatening invasive fungal infection caused by fungi belonging to mucorales order. Manifestations vary from localized disease to disseminated infection. Various types of mucormycosis are rhino-orbito-cerebral, pulmonary, cutaneous, gastrointestinal, renal, and disseminated. Pulmonary form is more common in patients with solid organ transplant and post hematopoietic stem cell transplantation. Multimodality treatment is used in the form of aggressive antifungals, surgery where possible, and control of underlying disease/factors. Here, we present an unusual presentation of pulmonary mucormycosis successfully managed with liposomal amphotericin B and surgical lobectomy.