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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 -
Heliyon Mar 2024amoebic encephalitis (BAE) is a rare and severe parasitic infection of the central nervous system. Its delayed diagnosis and treatment are often due to the lack of...
amoebic encephalitis (BAE) is a rare and severe parasitic infection of the central nervous system. Its delayed diagnosis and treatment are often due to the lack of specific clinical manifestations and its poor prognosis. Reported mortality rates reach around 95%. The Balamuthia mandrillaris is also known as the "brain-eating amoeba." Recently, the use of metagenomic next-generation sequencing (mNGS) in clinical settings has led to an increase in BAE diagnoses. A case report detailing the use of mNGS to diagnose granulomatous encephalitis caused by the Baramsi amoeba has improved clinicians' understanding of this disease and helped reduce misdiagnoses and missed diagnoses.
PubMed: 38434374
DOI: 10.1016/j.heliyon.2024.e26905 -
Therapeutic Advances in Infectious... 2024Granulomatous amebic encephalitis, caused by the free-living amebae or species, is a rare and deadly infectious syndrome with a current mortality rate of >90%. Much... (Review)
Review
Granulomatous amebic encephalitis, caused by the free-living amebae or species, is a rare and deadly infectious syndrome with a current mortality rate of >90%. Much work remains to define the optimal treatment for these infections. Here, we provide a comprehensive overview of the supporting evidence behind antimicrobials currently recommended by the Centers for Disease Control and Prevention (CDC) with updated statistics on survival rates and medication usage from the CDC Free-Living Ameba Database. We also discuss promising treatments, especially the emerging therapeutic agent nitroxoline, and provide recommendations for the next steps in this area.
PubMed: 38312848
DOI: 10.1177/20499361241228340 -
Frontiers in Microbiology 2023The phenotypic screening of drugs against , a neuropathogenic amoeba, involves two simultaneous phases: an initial step to test amoebicidal activity followed by an assay...
INTRODUCTION
The phenotypic screening of drugs against , a neuropathogenic amoeba, involves two simultaneous phases: an initial step to test amoebicidal activity followed by an assay for cytotoxicity to host cells. The emergence of three-dimensional (3D) cell cultures has provided a more physiologically relevant model than traditional 2D cell culture for studying the pathogenicity of . However, the measurement of ATP, a critical indicator of cell viability, is complicated by the overgrowth of in coculture with host cells during drug screening, making it challenging to differentiate between amoebicidal activity and drug toxicity to human cells.
METHODS
To address this limitation, we introduce a novel assay that utilizes three-dimensional hanging spheroid plates (3DHSPs) to evaluate both activities simultaneously on a single platform.
RESULTS AND DISCUSSION
Our study showed that the incubation of neurospheroids with clinically isolated trophozoites resulted in a loss of neurospheroid integrity, while the ATP levels in the neurospheroids decreased over time, indicating decreased host cell viability. Conversely, ATP levels in isolated trophozoites increased, indicating active parasite metabolism. Our findings suggest that the 3DHSP-based assay can serve as an endpoint for the phenotypic screening of drugs against , providing a more efficient and accurate approach for evaluating both parasite cytotoxicity and viability.
PubMed: 37744897
DOI: 10.3389/fmicb.2023.1190530 -
Microorganisms Feb 2024Free-living amoebae (FLA) are widely distributed protozoa in both natural and artificial environments such as drinking water. In addition to the ability of all FLA to...
Free-living amoebae (FLA) are widely distributed protozoa in both natural and artificial environments such as drinking water. In addition to the ability of all FLA to transport various pathogenic microorganisms, certain species, such as spp. or , have intrinsic pathogenic abilities and cause severe cerebral infections. Previous work has shown an enrichment of FLA cysts in biofilm developed in upper levels of Drinking Water Storage Towers (DWSTs), suggesting that differences in densities of FLA cysts may play a role in their unequal distribution in the water column. To evaluate this hypothesis, a model of a water column was created for this study and used to analyze the vertical distribution of cysts of the FLA , , and from 0 to 23 weeks. Interestingly, our data showed that the cysts of both and were enriched in upper water levels during their aging. However, cysts were equally distributed in the water column during the entire study. These results show that, in addition to the role of water level variation in the DWST, some FLA cysts can become less dense during their aging, which contributes to their enrichment in upper water and therefore biofilm levels.
PubMed: 38543525
DOI: 10.3390/microorganisms12030474 -
Frontiers in Microbiology 2023[This corrects the article DOI: 10.3389/fmicb.2023.1149145.].
[This corrects the article DOI: 10.3389/fmicb.2023.1149145.].
PubMed: 37954236
DOI: 10.3389/fmicb.2023.1304196 -
ACS Infectious Diseases Nov 2023Pathogenic free-living amoebae (pFLA) can cause life-threatening central nervous system (CNS) infections and warrant the investigation of new chemical agents to combat...
Pathogenic free-living amoebae (pFLA) can cause life-threatening central nervous system (CNS) infections and warrant the investigation of new chemical agents to combat the rise of infection from these pathogens. glucokinase (Glck), a key metabolic enzyme involved in generating glucose-6-phosphate, was previously identified as a potential target due to its limited sequence similarity with human Glck (Glck). Herein, we used our previously demonstrated multifragment kinetic target-guided synthesis (KTGS) screening strategy to identify inhibitors against pFLA glucokinases. Unlike the majority of previous KTGS reports, our current study implements a "shotgun" approach, where fragments were not biased by predetermined binding potentials. The study resulted in the identification of 12 inhibitors against 3 pFLA glucokinase enzymes─Glck, Glck (Glck), and Glck (Glck). This work demonstrates the utility of KTGS to identify small-molecule binders for biological targets where resolved X-ray crystal structures are not readily accessible.
Topics: Humans; Amoeba; Glucokinase; Naegleria fowleri; Balamuthia mandrillaris; Acanthamoeba castellanii
PubMed: 37820055
DOI: 10.1021/acsinfecdis.3c00284 -
Infection, Genetics and Evolution :... Apr 2024Balamuthia amoebic encephalitis (BAE), caused by Balamuthia mandrillaris, is a rare and life-threatening infectious disease with no specific and effective treatments...
INTRODUCTION
Balamuthia amoebic encephalitis (BAE), caused by Balamuthia mandrillaris, is a rare and life-threatening infectious disease with no specific and effective treatments available. The diagnosis of BAE at an early stage is difficult because of the non-specific clinical manifestations and neuroimaging.
CASE DESCRIPTION
A 52-year-old male patient, who had no previous history of skin lesions, presented to the emergency department with an acute headache, walking difficulties, and disturbance of consciousness. The patient underwent a series of examinations, including regular cerebrospinal fluid (CSF) studies and magnetic resonance imaging, and tuberculous meningoencephalitis was suspected. Despite being treated with anti-TB drugs, no clinical improvement was observed in the patient. Following corticosteroid therapy, the patient developed a rapid deterioration in consciousness with dilated pupils. Metagenomic next-generation sequencing (mNGS) revealed an unexpected central nervous system (CNS) amoebic infection, and the patient died soon after the confirmed diagnosis.
CONCLUSION
This study highlights the application of mNGS for the diagnosis of patients with suspected encephalitis or meningitis, especially those caused by rare opportunistic infections.
Topics: Male; Humans; Middle Aged; Infectious Encephalitis; Encephalitis; Balamuthia mandrillaris; Central Nervous System Protozoal Infections; Amebiasis; High-Throughput Nucleotide Sequencing
PubMed: 38382768
DOI: 10.1016/j.meegid.2024.105570 -
Radiology Case Reports May 2024We presented a case of a 66-year-old female whose initial symptom was headache without obvious inducement. The patient's condition progressed rapidly to a semi-coma...
We presented a case of a 66-year-old female whose initial symptom was headache without obvious inducement. The patient's condition progressed rapidly to a semi-coma state after symptomatic treatment. The F-FDG PET/CT scan revealed circular FDG hypermetabolism and central metabolic defect of the pons and left frontal lobe lesions. The combination of clinical findings, MRI, and Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid led to the diagnosis of Balamuthia mandrillaris encephalitis. The patient died 5 days after discharge.
PubMed: 38425772
DOI: 10.1016/j.radcr.2024.02.021