Insights into the evolution, virulence and speciation of and through multiomics analyses.

Babesiosis, caused by protozoan parasites of the genus , is an emerging tick-borne disease of significance for both human and animal health. parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of new species underscores the ongoing risk of zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental changes.

efficacy of next-generation dihydrotriazines and biguanides against babesiosis and malaria parasites.

and pathogens, the causative agents of babesiosis and malaria, are vector-borne intraerythrocytic protozoan parasites, posing significant threats to both human and animal health. The widespread resistance exhibited by these pathogens to various classes of antiparasitic drugs underscores the need for the development of novel and more effective therapeutic strategies. Antifolates have long been recognized as attractive antiparasitic drugs as they target the folate pathway, which is essential for the biosynthesis of purines and pyrimidines, and thus is vital for the survival and proliferation of protozoan parasites.

Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi.

Fungal infections, a leading cause of mortality among eukaryotic pathogens, pose a growing global health threat due to the rise of drug-resistant strains. New therapeutic strategies are urgently needed to combat this challenge. The PCA pathway for biosynthesis of Co-enzyme A (CoA) and Acetyl-CoA (AcCoA) from vitamin B5 (pantothenic acid) has been validated as an excellent target for the development of new antimicrobials against fungi and protozoa.

A set of diagnostic tests for detection of active Babesia duncani infection.

Objectives: Human babesiosis is an emerging and potentially fatal tick-borne disease caused by intraerythrocytic parasites of the Babesia genus. Among these, Babesia duncani is particularly notable for causing severe and life-threatening illness in humans. Accurate diagnosis and effective disease management hinge on the detection of active B.

A Set of Diagnostic Tests for Detection of Active Infection.

Unlabelled: Human babesiosis is a rapidly emerging and potentially fatal tick-borne disease caused by intraerythrocytic apicomplexan parasites of the genus. Among the various species of that infect humans, has been found to cause severe and life-threatening infections. Detection of active infection is critical for accurate diagnosis and effective management of the disease.

Effectiveness of Two New Endochin-like Quinolones, ELQ-596 and ELQ-650, in Experimental Mouse Models of Human Babesiosis.

Endochin-like quinolones (ELQs) define a class of small molecule antimicrobials that target the mitochondrial electron transport chain of various human parasites by inhibiting their cytochrome bc complexes. The compounds have shown potent activity against a wide range of protozoan parasites, including the intraerythrocytic parasites and , the agents of human malaria and babesiosis, respectively. First-generation ELQ compounds were previously found to reduce infection by and in animal models of human babesiosis but achieved a radical cure only in combination with atovaquone and required further optimization to address pharmacological limitations.

Multiomics analysis reveals MO1 as a distinct species and provides insights into its evolution and virulence.

Babesiosis, caused by protozoan parasites of the genus , is an emerging tick-borne disease of significance for both human and animal health. parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of various species underscores the ongoing risk of new zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental shifts impacting the distribution and transmission dynamics of parasites, their vectors, and reservoir hosts.

Tafenoquine-Atovaquone Combination Achieves Radical Cure and Confers Sterile Immunity in Experimental Models of Human Babesiosis.

Human babesiosis is a potentially fatal tick-borne disease caused by intraerythrocytic Babesia parasites. The emergence of resistance to recommended therapies highlights the need for new and more effective treatments. Here we demonstrate that the 8-aminoquinoline antimalarial drug tafenoquine inhibits the growth of different Babesia species in vitro, is highly effective against Babesia microti and Babesia duncani in mice and protects animals from lethal infection caused by atovaquone-sensitive and -resistant B.

Babesia BdFE1 esterase is required for the anti-parasitic activity of the ACE inhibitor fosinopril.

Effective and safe therapies for the treatment of diseases caused by intraerythrocytic parasites are impeded by the rapid emergence of drug resistance and the lack of novel drug targets. One such disease is human babesiosis, which is a rapidly emerging tick-borne illness caused by Babesia parasites. In this study, we identified fosinopril, a phosphonate-containing, FDA-approved angiotensin converting enzyme (ACE) inhibitor commonly used as a prodrug for hypertension and heart failure, as a potent inhibitor of Babesia duncani parasite development within human erythrocytes.

Uncovering the role of Rad51 in homologous recombination-mediated antigenic diversification in the human malaria parasite .

The human malaria parasite maintains the chronicity of infections through antigenic variation, a well-coordinated immune evasion mechanism. The most prominent molecular determinant of antigenic variation in this parasite includes the members of the multigene family. Homologous recombination (HR)-mediated genomic rearrangements have been implicated to play a major role in gene diversification.

Babesia duncani multi-omics identifies virulence factors and drug targets.

Babesiosis is a malaria-like disease in humans and animals that is caused by Babesia species, which are tick-transmitted apicomplexan pathogens. Babesia duncani causes severe to lethal infection in humans, but despite the risk that this parasite poses as an emerging pathogen, little is known about its biology, metabolic requirements or pathogenesis. Unlike other apicomplexan parasites that infect red blood cells, B.

A Chimeric Peptide Inhibits Red Blood Cell Invasion by Plasmodium falciparum with Hundredfold Increased Efficacy.

Inhibiting the formation of a tight junction between two malaria parasite proteins, apical membrane antigen 1 and rhoptry neck protein 2, crucial for red blood cell invasion, prevents progression of the disease. In this work, we have used a unique approach to design a chimeric peptide, prepared by fusion of the best features of two peptide inhibitors, that has displayed parasite growth inhibition ex vivo with nanomolar IC , which is 100 times better than any of its parent peptides. Furthermore, to gain structural insights, we computationally modelled the hybrid peptide on its receptor.

Babesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo.

Human babesiosis is a malaria-like illness caused by tick-borne intraerythrocytic Babesia parasites of the Apicomplexa phylum. Whereas several species of Babesia can cause severe disease in humans, the ability to propagate Babesia duncani both in vitro in human erythrocytes and in mice makes it a unique pathogen to study Babesia biology and pathogenesis. Here we report an optimized B.

Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients.

Background: SARS-CoV-2 infection has, as of April 2021, affected >133 million people worldwide, causing >2.5 million deaths. Because the large majority of individuals infected with SARS-CoV-2 are asymptomatic, major concerns have been raised about possible long-term consequences of the infection.

Effective Therapy Targeting Cytochrome Prevents Erythrocytic Development and Protects from Lethal Infection.

An effective strategy to control blood-borne diseases and prevent outbreak recrudescence involves targeting conserved metabolic processes that are essential for pathogen viability. One such target for and , the infectious agents of malaria and babesiosis, respectively, is the mitochondrial cytochrome protein complex, which can be inhibited by endochin-like quinolones (ELQ) and atovaquone. We used the tick-transmitted and culturable blood-borne pathogen to evaluate the structure-activity relationship, safety, efficacy, and mode of action of ELQs.

Benzimidazolinone-Free Peptide -Aminoanilides for Chemical Protein Synthesis.

The thioester surrogate 3,4-diaminobenzoic acid (Dbz) facilitates the efficient synthesis of peptide thioesters by Fmoc chemistry solid phase peptide synthesis and the optional attachment of a solubility tag at the C-terminus. The protection of the partially deactivated -amine of Dbz is necessary to obtain contamination-free peptide synthesis. The reported carbamate protecting groups promote a serious side reaction, benzimidazolinone formation.

A small-molecule inhibitor of the DNA recombinase Rad51 from synergizes with the antimalarial drugs artemisinin and chloroquine.

Malaria parasites repair DNA double-strand breaks (DSBs) primarily through homologous recombination (HR). Here, because the unrepaired DSBs lead to the death of the unicellular parasite , we investigated its recombinase, PfRad51, as a potential drug target. Undertaking an screening approach, we identified a compound, B02, that docks to the predicted tertiary structure of PfRad51 with high affinity.