-
Frontiers in Cellular and Infection... 2021Glycolytic enzymes play a crucial role in the anaerobic glycolysis of apicomplexan parasites for energy generation. Consequently, they are considered as potential...
Glycolytic enzymes play a crucial role in the anaerobic glycolysis of apicomplexan parasites for energy generation. Consequently, they are considered as potential targets for new drug development. Previous studies revealed that lactate dehydrogenase (LDH), a glycolytic enzyme, is a potential drug target in different parasites, such as , , , and . Herein, in order to investigate the structural basis of LDH in spp., we determined the crystal structure of apo (Bo) LDH at 2.67-Å resolution in the space group 1. A five-peptide insertion appears in the active pocket loop of BoLDH to create a larger catalytic pocket, like other protozoa (except for LDH) and unlike its mammalian counterparts, and the absence of this extra insertion inactivates BoLDH. Without ligands, the apo BoLDH takes R-state (relaxed) with the active-site loop open. This feature is obviously different from that of allosteric LDHs in T-state (tense) with the active-site loop open. Compared with allosteric LDHs, the extra salt bridges and hydrogen bonds make the subunit interfaces of BoLDH more stable, and that results in the absence of T-state. Interestingly, BoLDH differs significantly from BmLDH, as it exhibits the ability to adapt quickly to the synthetic co-factor APAD. In addition, the enzymatic activity of BoLDH was inhibited non-competitively by polyphenolic gossypol with a value of 4.25 μM, indicating that BoLDH is sensitive to the inhibition of gossypol and possibly to its new derivative compounds. The current work provides the structural basis of BoLDH for the first time and suggests further investigation on the LDH structure of other spp. That knowledge would indeed facilitate the screening and designing of new LDH inhibitors to control the intracellular proliferation of spp.
Topics: Animals; Babesia; Babesia microti; Catalytic Domain; Cryptosporidiosis; Cryptosporidium
PubMed: 35071043
DOI: 10.3389/fcimb.2021.790101 -
International Journal For Parasitology Feb 2019Babesia parasites infect a diverse range of vertebrate hosts, from penguins to pigs. Recently, the emergence of zoonotic Babesia infection has been increasing, and the... (Review)
Review
Babesia parasites infect a diverse range of vertebrate hosts, from penguins to pigs. Recently, the emergence of zoonotic Babesia infection has been increasing, and the list of species reported to infect humans continues to grow. Babesiosis represents a burgeoning veterinary and medical threat, and the need for novel therapeutic drugs to effectively target this diverse group of parasites is pressing. Here, we review the current culture systems that exist to study and manipulate Babesia parasites, and identify the scope and methods for target discovery and validation to identify novel, potent anti-babesial inhibitors. Challenges exist including difficulties in the culture systems of important zoonotic parasites, and there is a lack of integrated morphological and molecular data. While molecular approaches in several Babesia spp. has become a reality, the ability to rapidly identify and validate drug targets is hindered by a lack of sophisticated genetic tools to probe parasite biology. The minimal genome size and haploid nature of blood-stage Babesia parasites presents an opportunity to adapt techniques from related systems and characterise the druggable genomic space in a high-throughput way. The considerable diversity of parasites within the genus suggests the existence of highly divergent biology and polymorphism that could present a formidable barrier to the development of a pan-babesiacidal therapeutic strategy.
Topics: Antiprotozoal Agents; Babesia; Drug Development; Drug Discovery; Genetics, Microbial; Humans
PubMed: 30391230
DOI: 10.1016/j.ijpara.2018.09.005 -
Parasites & Vectors Apr 2020For most of the 20th century the causative agent of canine babesiosis, wherever it occurred in the world, was commonly referred to as Babesia canis. Early research, from... (Review)
Review
For most of the 20th century the causative agent of canine babesiosis, wherever it occurred in the world, was commonly referred to as Babesia canis. Early research, from the 1890s to the 1930s, had shown that there were three distinctly different vector-specific parasite entities occurring in specific geographical regions, that host response to infection ranged from subclinical to acute, and that immunity to one stock of the parasite did not necessarily protect against infection with other stocks. This substantial body of knowledge was overlooked or ignored for 50 years. In this review the first records and descriptions of the disease in four geographical regions were traced: sub-Saharan Africa, Europe, North Africa and Asia. Research leading to identification of the specific tick vector species involved is documented. Evidence is given of the growing realisation that there were substantial biological differences between stocks originating from different geographical regions. Etymological provenance for Babesia vogeli is proposed.
Topics: Africa South of the Sahara; Africa, Northern; Animals; Asia; Babesia; Babesiosis; Disease Vectors; Dog Diseases; Dogs; Europe
PubMed: 32312292
DOI: 10.1186/s13071-020-04062-w -
Parasites & Vectors Apr 2021Migratory birds can cross geographical and environmental barriers and are thereby able to facilitate transmission of tick-borne pathogens both as carriers of infected...
BACKGROUND
Migratory birds can cross geographical and environmental barriers and are thereby able to facilitate transmission of tick-borne pathogens both as carriers of infected ticks and as reservoirs of pathogenic microorganisms. Ixodes ricinus is one of the most abundant tick species in the Northern Hemisphere and a main vector of several Babesia species, some which pose a potential threat to human and animal health. At present only two cases of overt babesiosis in humans have so far been reported in Sweden. To better understand the potential role of birds as disseminators of zoonotic Babesia protozoan parasites, we investigated the presence of Babesia species in ticks removed from migratory birds.
METHODS
Ticks were collected from birds captured at Ottenby Bird Observatory, south-eastern Sweden, from March to November 2009. Ticks were molecularly identified to species, and morphologically to developmental stage, and the presence of Babesia protozoan parasites was determined by real-time PCR.
RESULTS
In total, 4601 migratory birds of 65 species were examined for tick infestation. Ticks removed from these birds have previously been investigated for the presence of Borrelia bacteria and the tick-borne encephalitis virus. In the present study, a total of 1102 ticks were available for molecular analysis of Babesia protozoan parasites. We found that 2.4% of the ticks examined, all I. ricinus, were positive for mammal-associated Babesia species. Out of all Babesia-positive samples, Babesia venatorum was the most prevalent (58%) species, followed by Babesia microti (38%) and Babesia capreoli (4.0%). B. venatorum and B. capreoli were detected in I. ricinus larvae, whereas B. microti was only present in I. ricinus nymphs. This supports the view that the two first-mentioned species are vertically (transovarially) transmitted in the tick population, in contrast to B. microti. The largest number of Babesia-infected ticks was removed from the common redstart (Phoenicurus phoenicurus) and European robin (Erithacus rubecula).
CONCLUSIONS
This study reveals that Babesia protozoan parasites are present in ticks infesting migratory birds in south-eastern Sweden, which could potentially lead to the dissemination of these tick-borne microorganisms into new areas, thus posing a threat to humans and other mammals.
Topics: Animal Migration; Animals; Babesia; Babesiosis; Female; Ixodes; Larva; Nymph; Passeriformes; Sweden; Tick Infestations; Zoonoses
PubMed: 33794970
DOI: 10.1186/s13071-021-04684-8 -
The Veterinary Record Jan 2020
Topics: Animals; Babesia; Babesiosis; United Kingdom
PubMed: 31974184
DOI: 10.1136/vr.m219 -
Emerging Microbes & Infections 2019Human babesiosis is an important tick-borne infectious disease. We investigated human babesiosis in the Gansu province and found that it is prevalent in this area with a...
Human babesiosis is an important tick-borne infectious disease. We investigated human babesiosis in the Gansu province and found that it is prevalent in this area with a prevalence of 1.3%. Results of gene sequencings indicate that 1.3% of patients were positive for . This initial report of human infections in Gansu Province should raise awareness of human babesiosis.
Topics: Adult; Animals; Babesia; Babesiosis; Bites and Stings; Female; Humans; Male; Middle Aged; Phylogeny; Tibet; Ticks
PubMed: 31244397
DOI: 10.1080/22221751.2019.1635431 -
Ticks and Tick-borne Diseases Feb 2016Babesiosis is an emerging tick-transmitted zoonosis in large parts of the world. In Sweden, the occurrence and diversity of Babesia species is largely unknown. In order...
Babesiosis is an emerging tick-transmitted zoonosis in large parts of the world. In Sweden, the occurrence and diversity of Babesia species is largely unknown. In order to estimate the exposure to Babesia from infected ticks, we collected questing Ixodes ricinus from several sites across southern Sweden during two consecutive field seasons and investigated the occurrence of Babesia species. We report for the first time the occurrence of the zoonotic species Babesia venatorum in Swedish ticks, with a prevalence of 1%. We also detected B. microti (prevalence 3.2%) and B. divergens (prevalence 0.2%). The incidence of Babesia in questing ticks is substantially lower than that of several other tick-borne diseases in Sweden. Nevertheless, babesiosis should not be neglected as a possible diagnosis following tick bites in humans and animals in Sweden.
Topics: Animals; Babesia; DNA, Protozoan; Host-Parasite Interactions; Ixodes; Larva; Nymph; Species Specificity; Sweden
PubMed: 26277447
DOI: 10.1016/j.ttbdis.2015.07.016 -
Polski Merkuriusz Lekarski : Organ... Jun 2020Lifelong withdrawal from the donor population of those who have been diagnosed with babesiosis must be used for transmission prevention.
UNLABELLED
Lifelong withdrawal from the donor population of those who have been diagnosed with babesiosis must be used for transmission prevention.
AIM
The aim of the study was a detection of Babesia antibodies level with the usage of experimental Babesia divergens whole-cell slide antigen and commercial B. microti immunofluorescence assay substrate slide (Fuller Laboratories, USA).
MATERIALS AND METHODS
Experimental B. divergens whole-cell slide antigen in addition to commercial B. microti IFA substrate slide was used to create a diagnostic kit for serum Babesia antibodies level detecting, as well as for a babesiosis serodiagnosis clinical trial of different origins blood samples (patients with Lyme disease, rheumatoid arthritis and toxoplasmosis; human blood donors; cattle).
RESULTS
Antibodies to B. divergens (5.4%) and B. microti (2.3%) were detected with higher (p <0.05) frequency at Lyme disease patients (16.7%) than at blood donors (1.7%). Diagnostically significant IgG titres (= 1:128) were found in 13.3% of blood samples from Lyme disease patients and 1.7% from blood donors. Specific IgM were also found in 13.3% blood samples from Lyme disease patients. Among blood samples from Lyme disease patients, in which diagnostically significant titres of Babesia antibodies were detected (16.7%), 60% of them were represented by IgG and IgM (rA= 0.63), and in 40% only one of them reached diagnostically significant titre. Conclusions. Advantages of babesiosis IFA diagnostics.
CONCLUSIONS
Advantages of babesiosis IFA diagnostics are combined with its significant disadvantages (principle of evaluation, low sensitivity in the initial period of the disease, probability of false positives, absence of validated test systems and research protocols for B. divergens and B. divergens-like species).
Topics: Animals; Babesia; Babesia microti; Babesiosis; Cattle; Humans; Immunoassay; Lyme Disease
PubMed: 32564041
DOI: No ID Found -
Parasites & Vectors Aug 2021Babesia species are intraerythrocytic Apicomplexan parasites that infect a wide range of vertebrate hosts. These pathogens are typically transmitted either by tick...
BACKGROUND
Babesia species are intraerythrocytic Apicomplexan parasites that infect a wide range of vertebrate hosts. These pathogens are typically transmitted either by tick vectors or by direct blood-to-blood contact, and may cause life-threatening clinical disease, such as thrombocytopenia, hemolytic anemia and acute renal failure, in canine hosts. While Babesia vogeli and Babesia gibsoni infections have both been reported in Oklahoma, reports of Babesia conradae infections have been limited to California.
METHODS
Four separate kennels of coyote-hunting dogs were identified in Oklahoma after the kennels had consulted with Oklahoma State University Boren Veterinary Medical Teaching Hospital (antemortem cases) or the Oklahoma Animal Disease Diagnostic Lab (postmortem cases). Upon owner consent, every accessible dog from each of the four kennels was briefly examined for ectoparasites, particularly ticks, and whole blood samples were collected in EDTA tubes. Clinically ill dogs were examined by a practicing veterinarian, and clinical signs included anorexia, vomiting, lethargy, fever and anemia. DNA was extracted from each blood sample, and a nested PCR was performed using general apicomplexan primers for the partial 18S rRNA gene. PCR products were electrophoresed in agarose matrix, and appropriately sized amplicons were sequenced. Sequences were compared to reference 18S rRNA gene sequences available in GenBank, and samples with > 98% homology to B. conradae (GenBank: AF158702) were considered positive. Babesia conradae-positive dogs were then treated with atovaquone (13.5 mg/kg three times per day) and azithromycin (10 mg/kg once daily) for 10 days and retested at 30 and 60 days post-treatment by PCR.
RESULTS
Of 40 dogs tested, 15 (37.5%) were positive for B. conradae with 98-99% sequence homology to B. conradae from California. All positive cases were coyote-hunting Greyhounds. Ectoparasites were not identified on any of the dogs at the time of blood collection. Treatment of clinically ill dogs with atovaquone and azithromycin resulted in complete clinical recovery in all treated dogs with negative follow-up PCR at 30 and 60 days post-treatment.
CONCLUSIONS
Collectively, this study (i) documents the occurrence of B. conradae in Oklahoma, (ii) highlights this pathogen as a differential to be considered when clinical signs are present, (iii) supports the use of atovaquone and azithromycin as effective treatment in these cases and (iv) demonstrates chronic subclinical carrier dogs serving as potential reservoirs of B. conradae infection to naïve dogs.
Topics: Animals; Babesia; Babesiosis; Coyotes; Disease Reservoirs; Dog Diseases; Dogs; Female; Male; Oklahoma; RNA, Ribosomal, 18S; Working Dogs
PubMed: 34391445
DOI: 10.1186/s13071-021-04897-x -
Veterinary Parasitology May 2006Small piroplasms as a cause of canine babesiosis in southern California were first documented in 1990. Initially these piroplasms were considered to be Babesia gibsoni,... (Review)
Review
Small piroplasms as a cause of canine babesiosis in southern California were first documented in 1990. Initially these piroplasms were considered to be Babesia gibsoni, the only small Babesia parasite known to infect dogs at that time. In the following decade, the use of molecular analysis made it clear that small canine Babesia in fact are comprised of at least three distinct species, and the isolates from dogs in southern California were not B. gibsoni. Molecular, antigenic, and morphological characteristics of the southern California species of canine piroplasm supported naming it as a distinct species, Babesia conradae. The renaming of this species prompted this literature review of small canine piroplasms in California in order to clarify clinical, diagnostic, epidemiological, and molecular characteristics of B. conradae in comparison to other small canine piroplasms. Clinical symptoms of B. conradae are similar to those of B. gibsoni; however, B. conradae infections may be more pathogenic, resulting in higher parasitaemia and more pronounced anaemia when compared with B. gibsoni-infected dogs. The immunofluorescent antibody test is the most commonly used test to diagnose B. conradae. It is important to specify which small Babesia species to test for since there is little serological cross reactivity between the small canine Babesia antigens or cross-detection in the newer molecular tests. Molecular characterization of B. conradae, based principally on the 18S small subunit rRNA gene, and recently the second internal transcribed spacer region, demonstrate that B. conradae is most closely related to piroplasms recovered from humans and animals in the western United States.
Topics: Animals; Babesia; Babesiosis; California; Dog Diseases; Dogs
PubMed: 16522352
DOI: 10.1016/j.vetpar.2006.01.045