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Scientific Reports Aug 2023Balamuthia mandrillaris is a pathogenic protozoan that causes a rare but almost always fatal infection of the central nervous system and, in some cases, cutaneous...
Balamuthia mandrillaris is a pathogenic protozoan that causes a rare but almost always fatal infection of the central nervous system and, in some cases, cutaneous lesions. Currently, the genomic data for this free-living amoeba include the description of several complete mitochondrial genomes. In contrast, two complete genomes with draft quality are available in GenBank, but none of these have a functional annotation. In the present study, the complete genome of B. mandrillaris isolated from a freshwater artificial lagoon was sequenced and assembled, obtaining an assembled genome with better assembly quality parameter values than the currently available genomes. Afterward, the genome mentioned earlier, along with strains V039 and 2046, were subjected to functional annotation. Finally, comparative genomics analysis was performed, and it was found that homologous genes in the core genome potentially involved in the virulence of Acanthamoeba spp. and Trypanosoma cruzi. Moreover, eleven of fifteen genes were identified in the three strains described as potential target genes to develop new treatment approaches for B. mandrillaris infections. These results describe proteins in this protozoan's complete genome and help prioritize which target genes could be used to develop new treatments.
Topics: Balamuthia mandrillaris; Virulence; Comparative Genomic Hybridization; Acanthamoeba; Genomics
PubMed: 37653073
DOI: 10.1038/s41598-023-41657-6 -
Antimicrobial Agents and Chemotherapy Jun 2022Infection with pathogenic free-living amoebae, including Naegleria fowleri, spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because...
Infection with pathogenic free-living amoebae, including Naegleria fowleri, spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because of catastrophic central nervous system involvement. Efficacious treatment options for these infections are lacking, and the mortality rate due to infection is high. Previously, we evaluated the N. fowleri glucokinase (Glck) as a potential target for therapeutic intervention, as glucose metabolism is critical for viability. Here, we extended these studies to the glucokinases from two other pathogenic free-living amoebae, including Acanthamoeba castellanii (Glck) and (Glck). While these enzymes are similar (49.3% identical at the amino acid level), they have distinct kinetic properties that distinguish them from each other. For ATP, Glck and Glck have apparent values of 472.5 and 41.0 μM, while Homo sapiens Glck (Glck) has a value of 310 μM. Both parasite enzymes also have a higher apparent affinity for glucose than the human counterpart, with apparent values of 45.9 μM (Glck) and 124 μM (Glck) compared to ~8 mM for Glck. Additionally, Glck and Glck differ from each other and other Glcks in their sensitivity to small molecule inhibitors, suggesting that inhibitors with pan-amoebic activity could be challenging to generate.
Topics: Acanthamoeba; Amebiasis; Amoeba; Balamuthia mandrillaris; Glucokinase; Humans; Naegleria fowleri
PubMed: 35604214
DOI: 10.1128/aac.02373-21 -
Infection and Drug Resistance 2023Central nervous system infection by is a rare and severe condition, which has a fatality rate of approximately 95% and often evades timely diagnosis due to its rarity...
Central nervous system infection by is a rare and severe condition, which has a fatality rate of approximately 95% and often evades timely diagnosis due to its rarity and non-specific clinical manifestations. Here, we report a case of encephalomyelomeningitis caused by in a male who presented with transient coma, nausea, and vomiting when working in a garbage dump. Initial magnetic resonance imaging (MRI) of the brain showed normal signals. Despite receiving steroids as well as antibacterial and antiviral treatment, he developed urinary and fecal dysfunction, inability to walk, and deterioration of consciousness. Both brain and spinal cord MRI revealed abnormal findings, and next-generation sequencing of the cerebrospinal fluid showed the presence of . A combination of fluconazole and albendazole was administered; however, the patient deteriorated gradually and died 30 days after the onset. We suggest the unbiased metagenomic sequencing of the affected tissues/CSF in patients with CNS infections that are difficult to diagnose or treat, and multiple tests at different stages of the disease may be required.
PubMed: 36756612
DOI: 10.2147/IDR.S400692 -
Journal of Pathology and Translational... Sep 2019We present the case of a 71-year-old man who was diagnosed with amoebic encephalitis caused by Balamuthia mandrillaris. He had rheumatic arthritis for 30 years and had...
We present the case of a 71-year-old man who was diagnosed with amoebic encephalitis caused by Balamuthia mandrillaris. He had rheumatic arthritis for 30 years and had undergone continuous treatment with immunosuppressants. First, he complained of partial spasm from the left thigh to the left upper limb. Magnetic resonance imaging revealed multifocal enhancing nodules in the cortical and subcortical area of both cerebral hemispheres, which were suggestive of brain metastases. However, the patient developed fever with stuporous mentality and an open biopsy was performed immediately. Microscopically, numerous amoebic trophozoites, measuring 20 to 25 µm in size, with nuclei containing one to four nucleoli and some scattered cysts having a double-layered wall were noted in the background of hemorrhagic necrosis. Based on the microscopic findings, amoebic encephalitis caused by Balamuthia mandrillaris was diagnosed. The patient died on the 10th day after being admitted at the hospital. The diagnosis of amoebic encephalitis in the early stage is difficult for clinicians. Moreover, most cases undergo rapid deterioration, resulting in fatal consequences. In this report, we present the first case of B. mandrillaris amoebic encephalitis with fatal progression in a Korean patient.
PubMed: 31121998
DOI: 10.4132/jptm.2019.05.14 -
Pathogens (Basel, Switzerland) Oct 2022Free-living amoebae (FLA) are protozoa widely distributed in the environment, found in a great diversity of terrestrial biomes. Some genera of FLA are linked to human... (Review)
Review
Free-living amoebae (FLA) are protozoa widely distributed in the environment, found in a great diversity of terrestrial biomes. Some genera of FLA are linked to human infections. The genus is currently classified into 23 genotypes (T1-T23), and of these some (T1, T2, T4, T5, T10, T12, and T18) are known to be capable of causing granulomatous amoebic encephalitis (GAE) mainly in immunocompromised patients while other genotypes (T2, T3, T4, T5, T6, T10, T11, T12, and T15) cause keratitis mainly in otherwise healthy patients. Meanwhile, is the causative agent of an acute infection called primary amoebic meningoencephalitis (PAM), while , like some genotypes, causes GAE, differing from the latter in the description of numerous cases in patients immunocompetent. Finally, other FLA related to the pathologies mentioned above have been reported; sp. is responsible for one case of amoebic encephalitis; has been found in cases of ocular damage, and its extraordinary capacity as endocytobiont for microorganisms of public health importance such as , and , among others. This review addressed issues related to epidemiology, updating their geographic distribution and cases reported in recent years for pathogenic FLA.
PubMed: 36297255
DOI: 10.3390/pathogens11101199 -
Frontiers in Neurology 2023Free-living amoebae (FLA) including spp., and can become pathogenic and cause severe cerebral infections, named primary amoebic meningoencephalitis (PAM),... (Review)
Review
BACKGROUND
Free-living amoebae (FLA) including spp., and can become pathogenic and cause severe cerebral infections, named primary amoebic meningoencephalitis (PAM), granulomatous amoebic encephalitis (GAE), and balamuthia amoebic encephalitis (BAE), respectively. FLA encephalitis has been reported across China, but the clinical data descriptions and analytical results of these different reports vary widely. Currently, no consensus treatment has been established. We conduct a systematic review to evaluate the exposure location, clinical symptoms, diagnosis, treatment, and prognosis of three FLA encephalitis and aim to reveal the differences between three FLA encephalitis in China.
METHODS
We used MEDLINE (PubMed interface), EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang database, and China Biology Medicine disc (CBMdisc) databases for literatures published and manually retrieve the hospital records of our hospital. The search time was up to August 30, 2022, with no language restrictions.
RESULTS
After excluding possible duplicate cases, a total of 48 patients of three FLA encephalitis were collected. One from the medical records of our hospital and 47 patients from 31 different studies. There were 11 patients of PAM, 10 patients of GAE, and 27 patients of BAE. The onset of PAM is mostly acute or subacute, and the clinical symptoms are acute and fulminant hemorrhagic meningoencephalitis. Most patients with GAE and BAE have an insidious onset and a chronic course. A total of 21 BAE patients (77.8%) had skin lesions before onset of symptoms. Additionally, 37 cases (77.1%) were diagnosed with FLA encephalitis before death. And there were 4 of PAM, 2 of GAE, and 10 of BAE diagnosed using next generation sequencing. No single agent can be proposed as the ideal therapy by itself. Only 6 cases were successfully treated.
CONCLUSIONS
This review provides an overview of the available data and studies of FLA encephalitis in China and identify some potential differences. FLA encephalitis is a rare but pathogenic infection, and physicians should early identify this encephalitis to improve survival.
PubMed: 36846140
DOI: 10.3389/fneur.2023.1100785 -
Parasites & Vectors Jun 2022Environmental protozoa need an adaptation mechanism to survive drastic changes in niches in the human body. In the brain parenchyma, Balamuthia mandrillaris...
BACKGROUND
Environmental protozoa need an adaptation mechanism to survive drastic changes in niches in the human body. In the brain parenchyma, Balamuthia mandrillaris trophozoites, which are causative agents of fatal brain damage, must acquire nutrients through the ingestion of surrounding cells. However, the mechanism deployed by the trophozoites for cellular uptake remains unknown.
METHODS
Amoebic ingestion of human neural cell components was investigated using a coculture system of clinically isolated B. mandrillaris trophozoites and human neuroblastoma SH-SY5Y cells. Cell-to-cell interactions were visualized in a three-dimensional manner using confocal and holotomographic microscopes.
RESULTS
The B. mandrillaris trophozoites first attached themselves to human neuroblastoma SH-SY5Y cells and then twisted themselves around the cytoplasmic bridge. Based on fluorescence-based cell tracking, the B. mandrillaris trophozoites then inserted invadopodia into the cytoplasm of the human cells. Subsequently, the human protein-enriched components were internalized into the trophozoites in the form of nonmembranous granules, whereas the human lipids were dispersed in the cytoplasm. Intervention of trogocytosis, a process involving nibbling on parts of the target cells, failed to inhibit this cellular uptake.
CONCLUSIONS
Human cell ingestion by B. mandrillaris trophozoites likely differs from trogocytosis, suggesting that a pathogen-specific strategy can be used to ameliorate brain damage.
Topics: Amebiasis; Animals; Balamuthia mandrillaris; Brain; Humans; Neuroblastoma; Trogocytosis; Trophozoites
PubMed: 35761411
DOI: 10.1186/s13071-022-05306-7 -
Epidemiology and Infection Jul 2015Balamuthia mandrillaris is an emerging cause of encephalitis in humans. The transmission dynamics are poorly understood due to the high fatality rate and the sporadic...
Balamuthia mandrillaris is an emerging cause of encephalitis in humans. The transmission dynamics are poorly understood due to the high fatality rate and the sporadic nature of cases. Seventy-two soil samples were collected from beaches and the banks of lagoons, rivers, ponds, mineral springs and streams from across Jamaica and assayed for the presence of B. mandrillaris. Seventy-nine sites were sampled and the mitochondrial 16S rDNA gene of B. mandrillaris was amplified and sequenced to confirm the presence of the amoeba. One isolate of B. mandrillaris was recovered from soil from mineral spring which hosts an informal therapeutic mud bath business. Although B. mandrillaris is less frequently isolated from soil than other free-living amoebae, rubbing mud containing the organism onto the skin increases the likelihood of exposure and infection. This first report on the isolation of B. mandrillaris in the Caribbean and its presence in soil where human contact is likely warrants further investigation using serological methods to elucidate exposure patterns.
Topics: Balamuthia mandrillaris; DNA, Mitochondrial; DNA, Ribosomal; Data Collection; Environmental Microbiology; Humans; Jamaica; Molecular Sequence Data; Mud Therapy; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 25335452
DOI: 10.1017/S0950268814002842 -
Emerging Microbes & Infections Dec 2020infection is a rare and fatal disease. We have recorded 28 cases of infection during the past 20 years. Eighteen patients (64%) were male and 10 (36%) were female....
infection is a rare and fatal disease. We have recorded 28 cases of infection during the past 20 years. Eighteen patients (64%) were male and 10 (36%) were female. Patient age ranged from 3 to 74 (mean, 27) years. Patient locations were distributed among 12 Provinces in China. Twenty-seven (96%) patients lived in rural areas, and 17 (61%) patients reported a history of trauma before the appearance of skin lesions. All cases presented with skin lesions as the primary symptom, and 16 (57%) cases developed encephalitis. Histopathology of skin lesions revealed granulomatous changes with histiocytes, lymphocytes, and plasma cells infiltration. Amebas were identified in all cases with immunohistochemical staining. Follow-up information was available in 27 (96%) cases. Fifteen (56%) patients died due to encephalitis and 12 (44%) were free of disease after treatment. Our results show that the clinical characteristics of infection in China are very different from those in the US. Infection of traumatized skin may play an important role in the pathogenesis of the disease in China. Encephalitis usually develops 3-4 years after skin lesions in Chinese cases. Patients with only skin lesions have a higher cure rate than patients with encephalitis.
Topics: Adolescent; Adult; Aged; Amebiasis; Balamuthia mandrillaris; Central Nervous System Protozoal Infections; Child; Child, Preschool; China; Female; Humans; Infectious Encephalitis; Male; Middle Aged; Mortality; Retrospective Studies; Rural Population; Skin Diseases, Parasitic; Young Adult
PubMed: 33048025
DOI: 10.1080/22221751.2020.1835447