Current issues in heartworm chemotherapy
Several issues that affect prevention and treatment of heartworm infections require more intensive research. The incidence of heartworm infection in the USA is increasing, but the factors that underlie this trend remain incompletely understood. The contributions of climate change, vector range expansion, client compliance and resistance to macrocyclic lactones (ML) are likely interrelated and require investigation. Molecular-level research has not yet identified the causative mechanisms...
Beyond overlap in kinetoplastid interactomes
Independent protein-protein interaction networks in kinetoplastid parasites show little overlap, often interpreted as biological divergence. We argue that this pattern largely reflects fragmented sampling. Integrating interactomes from Trypanosoma brucei, Trypanosoma cruzi, and Leishmania donovani improves functional coverage and interpretability while preserving lineage-specific assemblies, providing a framework for hypothesis generation across species.
Comparative performance of structural aligners in functional domain annotation
Accurate protein domain annotation is essential for inferring protein function, and databases such as Pfam provide sequence-derived signatures for thousands of domain families. Because protein structure is more evolutionarily conserved than sequence, structure-based searches can detect homologous relationships even at low sequence identity (typically below 30%), where pairwise sequence aligners often lose sensitivity. Here, we leverage AlphaFold-derived structures of Pfam domain instances to...
Interpreting Microbiome Signatures with MicrobiomeNet
MicrobiomeNet (https://microbiomenet.com) is a web-based platform developed to provide functional insights into microbiome signatures using genome-scale metabolic models (GEMs). It currently hosts 12,400 GEMs and around 6 million microbial signatures. Users can start by searching microbes, metabolites, genes, or enzymes, and perform common tasks such as to characterize the metabolic capacity for a given microbe, to explore known microbial associations, as well as to understand potential...
Etiologies of community-acquired febrile illness identified by TaqMan Array Card qPCR on blood samples: a systematic review and meta-analysis
Community-acquired febrile illness presents a significant diagnostic challenge. The TaqMan Array Card (TAC) enables simultaneous detection of many bacterial, viral, parasitic, and fungal pathogens. This systematic review aimed to characterize the etiologies of community-acquired fever diagnosed by TAC directly on blood specimens. A systematic search of PubMed, Scopus, Embase, and Web of Science (from inception to January 2026 in English) identified studies using TAC to detect pathogens directly...
Genomic Characterization of <em>Salmonella</em> Isolates Causing Infections in Children with Sickle Cell Disease in Dakar, Senegal
Salmonella is a major bacterial pathogen in low-income countries, where it circulates among humans, animals, and the environment. Children with sickle cell disease (SCD) are particularly vulnerable to severe Salmonella infections. This study aimed to characterize Salmonella isolates causing infections in Senegalese children with SCD. Using antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatic analysis, we investigated antibiotic resistance, serovar diversity, and...
Current Applications and Immunological Considerations of <em>Salmonella enterica</em> Serovar Typhimurium as a Vaccine Vector
Live attenuated Salmonella enterica serovar Typhimurium has been investigated for decades as an orally delivered vaccine vector due to its ability to target the intestinal mucosa and engage both innate and adaptive immune responses. In humans, S. Typhimurium infection is largely restricted to the gastrointestinal tract, distinguishing it from Salmonella Typhi and providing a rationale for its use in mucosal vaccine strategies. In this review, we discuss the biological features of S. Typhimurium...
Stunning Intricacies of RNA Editing Complexes RECC, RESC, and REH2C: Functional Organization, Developmental Regulation, and Evolutionary History in Kinetoplastid Protists
RNA metabolism in kinetoplastid protists (Kinetoplastea), including trypanosomes and Leishmania, involves unique post-transcriptional mitochondrial RNA editing that creates translatable mRNAs through uridine (U) insertions and deletions (U-indels) directed by antisense guide RNAs (gRNAs). Like other biological processes that require specific RNA targeting, this system faces several challenges beyond coordinating its many components: assembling mRNA-gRNA hybrids, recognizing hundreds of sites,...
Development of a quantitative self-assessment tool for hospital antimicrobial stewardship and infection control programs: a step towards standardizing clinical studies
CONCLUSION: This quantitative scoring scheme represents a promising step towards standardizing assessments of AMS and IPC programs in high-income settings, enabling external comparisons and supporting future clinical studies. Further validation is needed to refine its predictive validity and ensure its utility in diverse healthcare settings.
Metabolomic analysis of macrocyclic lactone susceptible and resistant isolates of Dirofilaria immitis
Resistance to macrocyclic lactone (ML) preventives in the canine heartworm Dirofilaria immitis is an emerging concern worldwide. Although ML-resistant isolates of D. immitis are genetically distinct from wildtype populations, little is known about their drug resistance mechanisms. To address this gap, we used untargeted metabolomics to characterize and compare the excreted/secreted metabolic profile of drug-susceptible Missouri (MO) and -resistant JYD-34 isolates in the presence or not of...
Telomere-to-telomere assembly detects genomic diversity in Canadian strains of Borrelia burgdorferi
Borrelia burgdorferi, the bacteria causing Lyme disease, has a complex genome comprising a linear chromosome and multiple linear and circular plasmids. The atypical hairpin telomeres and the highly paralogous plasmids complicate genome assembly. We develop a genome assembly pipeline using both long and short reads to overcome these challenges. Using long reads, we assemble the hairpin telomeres of the linear replicons, an lp28-1a plasmid subtype, and circular plasmids of nine B. burgdorferi...
Multiomic analysis of clonal development reveals new regulators of leukemic cell growth
Mechanisms driving the increase in cell growth in developing leukemia are not fully understood. We focused on epigenomic regulation of this process by analyzing the changes of chromatin marks and gene expression in leukemic cell clones as they progressed toward increased proliferation in a mouse model of acute myeloid leukemia (AML). This progression was characterized by gradual modulation of chromatin states and gene expression across the genome, with a surprising preferential trend of...
Ultra-rapid nanoplasmonic colorimetry in microfluidics for antimicrobial susceptibility testing directly from specimens
Antimicrobial susceptibility testing (AST) technologies that rapidly identify pathogenic bacteria and their resistance phenotypes are critical in addressing the antimicrobial resistance crisis, enabling timely and precise antibiotic treatment decisions. We present a modular automated platform based on nanoplasmonic colorimetry in microfluidics for parallel bacterial identification and phenotypic profiling of AST (QolorPhAST), achieving an eightfold enhancement in detection rapidity. QolorPhAST...
Enzyme Assays for Phosphoinositide Kinases and Phosphatases and Inhibitor Screens
In vitro enzyme assays provide sensitive and quantitative approaches to studying activity, identifying substrates or performing inhibitor analysis. These approaches can help to study enzymes that regulate different cellular processes in an organism. In addition, enzyme assays can be used to screen protein inhibitors to identify novel drug candidates. In eukaryotes, phosphatidylinositol kinase and phosphatase are enzymes that regulate the level of phosphorylated phosphatidylinositol, which...
Improving the tuberculosis infection care cascade among migrants in Canada: a cost-effectiveness modelling study
BACKGROUND: Tuberculosis elimination requires expanded use of preventive treatment. However, adherence to the tuberculosis infection cascade of care is often an issue, notably in vulnerable groups such as migrants. We aimed to assess a person-centred approach to tuberculosis screening and treatment using facilitators, comparing strategies for tuberculosis prevention among new migrants to Canada.
GeoSentinel Analysis of Travelers' Diarrhea Antimicrobial Resistance Patterns
CONCLUSIONS AND RELEVANCE: In this cross-sectional study of travelers' diarrhea antimicrobial resistance patterns, there was marked variability of nonsusceptibility to 2 major classes of antibiotics commonly used for treating travelers' diarrhea among global regions. Antimicrobial susceptibility from culture should be obtained when possible, including after pathogen detection by culture-independent methods. These findings may help inform strategies for self-treatment and clinician management of...
How the One Health approach can make effective the World Health Organization's recommendations on integrated management of childhood illnesses: Case of community-based home management of malaria in the <em>Ferlo</em> of Matam, Senegal
CONCLUSION: Thus, CBHM-Ferlo strategy improved the care of childhood illness in Matam in 2024, and above all highlights the added value of One Health and transdisciplinary approaches.
Development and evaluation of quadruplex droplet digital PCR assay for rapid detection of molecular markers associated with macrocyclic lactone resistance and susceptibility in Dirofilaria immitis
Due to climate change and human interventions, there has been an increase in D. immitis infections, underscoring the necessity for monitoring the spread and extent of resistance. In our prior research, we introduced a rapid test utilizing four predominant SNP markers at loci 15709 (SNP1), 30575 (SNP2), 21554 (SNP3), and 9400 (SNP7) linked to ML resistance. Our findings highlighted SNP1 and SNP2 as potent predictive markers, offering suitability for the rapid detection and monitoring of drug...
Topically administered macrocyclic lactone products, including eprinomectin, demonstrate comparable neurological safety in cats based on pharmacovigilance data
CONCLUSIONS: An evaluation of pharmacovigilance data from 2 different sources revealed no evidence of greater proportional reporting for neurological AEs specific to the use of eprinomectin-containing products in cats than for other MLs or emodepside.
