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PLoS Pathogens Jun 2024The bloodstream form of Trypanosoma brucei expresses large poly-N-acetyllactosamine (pNAL) chains on complex N-glycans of a subset of glycoproteins. It has been...
The bloodstream form of Trypanosoma brucei expresses large poly-N-acetyllactosamine (pNAL) chains on complex N-glycans of a subset of glycoproteins. It has been hypothesised that pNAL may be required for receptor-mediated endocytosis. African trypanosomes contain a unique family of glycosyltransferases, the GT67 family. Two of these, TbGT10 and TbGT8, have been shown to be involved in pNAL biosynthesis in bloodstream form Trypanosoma brucei, raising the possibility that deleting both enzymes simultaneously might abolish pNAL biosynthesis and provide clues to pNAL function and/or essentiality. In this paper, we describe the creation of a TbGT10 null mutant containing a single TbGT8 allele that can be excised upon the addition of rapamycin and, from that, a TbGT10 and TbGT8 double null mutant. These mutants were analysed by lectin blotting, glycopeptide methylation linkage analysis and flow cytometry. The data show that the mutants are defective, but not abrogated, in pNAL synthesis, suggesting that other GT67 family members can compensate to some degree for loss of TbGT10 and TbGT8. Despite there being residual pNAL synthesis in these mutants, certain glycoproteins appear to be particularly affected. These include the lysosomal CBP1B serine carboxypeptidase, cell surface ESAG2 and the ESAG6 subunit of the essential parasite transferrin receptor (TfR). The pNAL deficient TfR in the mutants continued to function normally with respect to protein stability, transferrin binding, receptor mediated endocytosis of transferrin and subcellular localisation. Further the pNAL deficient mutants were as viable as wild type parasites in vitro and in in vivo mouse infection experiments. Although we were able to reproduce the inhibition of transferrin uptake with high concentrations of pNAL structural analogues (N-acetylchito-oligosaccharides), this effect disappeared at lower concentrations that still inhibited tomato lectin uptake, i.e., at concentrations able to outcompete lectin-pNAL binding. Based on these findings, we recommend revision of the pNAL-dependent receptor mediated endocytosis hypothesis.
PubMed: 38935804
DOI: 10.1371/journal.ppat.1012333 -
PloS One 2024The economic impact of gastrointestinal (GI) nematode infections on livestock production is well documented worldwide. Increasing evidence supports the hypothesis that...
The economic impact of gastrointestinal (GI) nematode infections on livestock production is well documented worldwide. Increasing evidence supports the hypothesis that parasite colonization induces significant changes in the GI tract environment and, therefore, in the landscape where the microbiota and parasites occur. Understanding the interactions between bacterial and parasite populations in the digestive tract of livestock may be useful to design parasite control strategies based on microbiota modification. The aims of this work were to investigate the impact of the oxytetracycline-mediated manipulation of the gut microbial community on the composition of GI nematode populations in naturally infected sheep and to explore changes in the GI microbial communities after nematode population treatment with the anthelmintic compound monepantel. Extensive manipulation of the GI microbiota with a therapeutic dose of the long-acting oxytetracycline formulation did not induce significant changes in the GI nematode burden. The gut microbiota of treated animals returned to control levels 17 days after treatment, suggesting strong resilience of the sheep microbial community to antibiotic-mediated microbiota perturbation. A significant decrease of the bacterial Mycoplasmataceae family (Log2FC = -4, Padj = 0.001) and a marked increase of the Methanobacteriaceae family (Log2FC = 2.9, Padj = 0.018) were observed in the abomasum of sheep receiving the monepantel treatment. While a comprehensive evaluation of the interactions among GI mycoplasma, methanobacteria and nematode populations deserves further assessment, the bacteria-nematode population interactions should be included in future control programs in livestock production. Understanding how bacteria and parasites may influence each other in the GI tract environment may substantially contribute to the knowledge of the role of microbiota composition in nematode parasite establishment and the role of the parasites in the microbiota composition.
Topics: Animals; Sheep; Gastrointestinal Microbiome; Sheep Diseases; Nematode Infections; Nematoda; Oxytetracycline; Gastrointestinal Tract; Aminoacetonitrile; Bacteria
PubMed: 38935803
DOI: 10.1371/journal.pone.0306390 -
PLoS Pathogens Jun 2024The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes...
The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation, including the importance of phosphorylation, remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals crucial for malaria parasite development.
PubMed: 38935780
DOI: 10.1371/journal.ppat.1012360 -
ELife Jun 2024The Zanzibar archipelago of Tanzania has become a low-transmission area for . Despite being considered an area of pre-elimination for years, achieving elimination has...
BACKGROUND
The Zanzibar archipelago of Tanzania has become a low-transmission area for . Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania and continued local transmission.
METHODS
To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 isolates collected across Zanzibar and in Bagamoyo district on the coastal mainland from 2016 to 2018.
RESULTS
Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to the rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within , suggests ongoing low-level local transmission. We also identified highly related parasites across that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes.
CONCLUSIONS
Our data support importation as a main source of genetic diversity and contribution to the parasite population in Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive to malaria reemergence due to susceptible hosts and competent vectors.
FUNDING
This research was funded by the National Institutes of Health, grants R01AI121558, R01AI137395, R01AI155730, F30AI143172, and K24AI134990. Funding was also contributed from the Swedish Research Council, Erling-Persson Family Foundation, and the Yang Fund. RV acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 program supported by the European Union. RV also acknowledges funding by Community Jameel.
Topics: Tanzania; Plasmodium falciparum; Malaria, Falciparum; Humans; Genotype
PubMed: 38935423
DOI: 10.7554/eLife.90173 -
Indian Journal of Public Health Oct 2023The research paper explores the burden and associated factors of intestinal parasitic infections among pregnant women in Sikkim, India, categorized as neglected tropical...
The research paper explores the burden and associated factors of intestinal parasitic infections among pregnant women in Sikkim, India, categorized as neglected tropical diseases affecting 1.5 billion globally, with higher rates in tropical regions. These infections pose significant health risks, causing anemia, poor maternal-perinatal health, and perpetuating generational undernutrition and recurrent infections. A cross-sectional study of 100 pregnant women in Sikkim aimed to determine the burden of intestinal parasitosis and associated sociodemographic factors. It reported a lower prevalence compared to similar studies, with Giardia Lamblia as the dominant parasite. The study found a significant link between intestinal parasitosis and anemia. In conclusion, the paper recommends routine screening and deworming for pregnant women with low hemoglobin levels, emphasizing health education and awareness about intestinal parasitosis during pregnancy, especially in resource-limited settings. Adherence to India's National Guidelines for Deworming during pregnancy is crucial.
Topics: Humans; Female; India; Pregnancy; Cross-Sectional Studies; Adult; Intestinal Diseases, Parasitic; Young Adult; Tertiary Care Centers; Prevalence; Pregnancy Complications, Parasitic; Socioeconomic Factors; Anemia; Prenatal Care; Adolescent
PubMed: 38934813
DOI: 10.4103/ijph.ijph_1633_22 -
Infection and Drug Resistance 2024Persistent infections caused by (), which are resistant to antibiotic treatment, pose a growing global public health concern. Biofilm formation is known to be...
BACKGROUND
Persistent infections caused by (), which are resistant to antibiotic treatment, pose a growing global public health concern. Biofilm formation is known to be associated with persistent infections due to its role in enhancing antimicrobial resistance and the tolerance of many pathogenic bacteria.
OBJECTIVE
This study aims to evaluate the biofilm formation of clinical isolates of and its impact on antibiotic eradication.
METHODS
The thickness, morphology, and structure of biofilms derived from nine strains were examined using confocal laser scanning microscopy, scanning electron microscopy, and transmission electron microscopy. Subsequently, the susceptibility of both planktonic and biofilm bacteria was assessed through the determination of minimum inhibitory concentration and minimum biofilm eradication concentration for amoxicillin, clarithromycin, levofloxacin, and tetracycline.
RESULTS
The results revealed varying biofilm thicknesses and densities among the strains, characterised by the presence of numerous filaments intertwining and connecting bacterial cells. Additionally, several cases exhibited susceptibility based on MIC measurements but resistance according to MBEC measurements, with MBEC indicating a higher resistance rate. Pearson Correlation analysis demonstrated a positive correlation between biofilm thickness and MBEC results (0 < < 1), notably significant for amoxicillin ( = 0.801, = 0.009) and tetracycline ( = 0.696, = 0.037).
CONCLUSION
Different strains of exhibit variations in their capacity to release outer membrane vesicles (OMVs) and form biofilms. Biofilm formation can influence the effectiveness of amoxicillin and tetracycline in eradicating susceptible bacterial strains.
PubMed: 38933776
DOI: 10.2147/IDR.S468126 -
Veterinary Medicine International 2024Anaplasmosis, transmitted biologically and mechanically, is one of the most prevalent diseases responsible for high production costs worldwide. In this research, the...
Anaplasmosis, transmitted biologically and mechanically, is one of the most prevalent diseases responsible for high production costs worldwide. In this research, the prevalence and risk factors of anaplasmosis in Simmental cattle raised in the Peruvian Amazon were evaluated. 266 blood samples were collected from bovines of different categories such as calves male, calves females, heifers <1.3 years, heifers >1.3 years, steers, bulls, and cows from the districts of Omia and Molinopampa. The enzyme-linked immunosorbent assay (ELISA) technique was used to detect antibodies against . Of the 266 animals sampled, 67% were positive for A. marginale. A higher prevalence was determined in the district of Omia (99.3%), while in the district of Molinopampa, 28.7% was obtained. A prevalence of was recorded in females (67.7%) and in males (64.8%) ( > 0.05). There is a significant association of the disease with the category of cattle, verifying the highest prevalence of in calves male, heifer >1.3 years, and bull. The multiple correspondence analysis shows that San Mateo, Puma Marca, Mashuyacu, Primavera, and Los Olivos have a higher prevalence of anaplasmosis, associated with altitude of 1701-2000 m, spray baths and paddock rotation. Anaplasmosis is prevalent in Simmental cattle from the Peruvian Amazon, with a higher incidence in Omia and in females, considering May to August the critical months and the altitude less than 2000 meters above sea level.
PubMed: 38933691
DOI: 10.1155/2024/4634440 -
China CDC Weekly Jun 2024Traditional methods for determining radiation dose in nuclear medicine include the Monte Carlo method, the discrete ordinate method, and the point kernel integration...
INTRODUCTION
Traditional methods for determining radiation dose in nuclear medicine include the Monte Carlo method, the discrete ordinate method, and the point kernel integration method. This study presents a new mathematical model for predicting the radiation dose rate in the vicinity of nuclear medicine patients.
METHODS
A new algorithm was created by combining the physical model of "cylinder superposition" of the human body with integral analysis to assess the radiation dose rate in the vicinity of nuclear medicine patients.
RESULTS
The model accurately predicted radiation dose rates within distances of 0.1-3.0 m, with a deviation of less than 11% compared to observed rates. The model demonstrated greater accuracy at shorter distances from the radiation source, with a deviation of only 1.55% from observed values at 0.1 m.
DISCUSSION
The model proposed in this study effectively represents the spatial and temporal distribution of the radiation field around nuclear medicine patients and demonstrates good agreement with actual measurements. This model has the potential to serve as a radiation dose rate alert system in hospital environments.
PubMed: 38933663
DOI: 10.46234/ccdcw2024.108 -
China CDC Weekly Jun 2024Echinococcosis exhibits a global distribution. In China, the primary endemic area is the northwest region. In December 2023, we documented a case of echinococcosis in an...
WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?
Echinococcosis exhibits a global distribution. In China, the primary endemic area is the northwest region. In December 2023, we documented a case of echinococcosis in an individual lacking any travel or residential history in endemic regions.
WHAT IS ADDED BY THIS REPORT?
This is the first laboratory-confirmed case of hepatic echinococcosis reported in Guangdong Province, associated with the G7 genotype of (). The most probable mode of transmission is a local infection resulting from introduced from endemic regions.
WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?
As the circulation of agricultural products increases, it is essential to enhance the quarantine and management of livestock from epidemic areas to prevent and control the spread of echinococcosis to non-epidemic regions.
PubMed: 38933662
DOI: 10.46234/ccdcw2024.109 -
Antibody Therapeutics Apr 2024The recent discovery of public antibodies targeting -encoded repetitive interspersed families of polypeptides (RIFINs), which contain extracellular immunoglobulin-like... (Review)
Review
The recent discovery of public antibodies targeting -encoded repetitive interspersed families of polypeptides (RIFINs), which contain extracellular immunoglobulin-like domains from LAIR1 or LILRB1, constitutes a significant step forward in comprehending the reactivity of the parasite. These antibodies arise from unique B cell clones and demonstrate extensive cross-reactivity through their interaction with RIFINs. LAIR1 and LILRBs are specialized type I transmembrane glycoproteins, classified as immune inhibitory receptors, restricted to primates and mainly found on hematopoietic cells. They are instrumental in modulating interactions within the tumor microenvironment and across the immune system, and are increasingly recognized as important in anti-cancer immunotherapy and pathogen defense. The presence of LAIR1/LILRB1-containing antibodies offers new insights into malaria parasite evasion strategies and the immune system's response. Additionally, the innovative method of integrating extra exons into the antibody switch region is a noteworthy advancement, enriching the strategies for the generation of a varied array of bispecific and multispecific antibodies.
PubMed: 38933531
DOI: 10.1093/abt/tbae008