Pharmacogenomics of Cytauxzoon felis cytochrome b: implications for atovaquone and azithromycin therapy in domestic cats with cytauxzoonosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Schreeg ME
PROVIDER: S-EPMC3754644 | biostudies-literature | 2013 Sep
REPOSITORIES: biostudies-literature
Publications
Pharmacogenomics of Cytauxzoon felis cytochrome b: implications for atovaquone and azithromycin therapy in domestic cats with cytauxzoonosis.
Schreeg Megan E ME Marr Henry S HS Tarigo Jaime J Cohn Leah A LA Levy Michael G MG Birkenheuer Adam J AJ
Journal of clinical microbiology 20130619 9
Cytauxzoon felis, an emerging virulent protozoan parasite that infects domestic cats, is treated with atovaquone and azithromycin (A&A). Atovaquone targets parasite cytochrome b. We characterized the C. felis cytochrome b gene (cytb) in cats with cytauxzoonosis and found a cytb genotype that was associated with survival in A&A-treated cats. ...[more]
Similar Datasets
Project description:Background: Atovaquone and azithromycin (A&A) with supportive care improve survival rates in cats with cytauxzoonosis. Resistance to atovaquone via parasite cytochrome b gene (cytb) mutations occurs in other Apicomplexan protozoans but is not described in Cytauxzoon felis.Objective: To serially characterize the C. felis cytb sequences from a cat that remained persistently infected after A&A treatment.Animal: A cat with naturally occurring C. felis infection.Methods: Case report of the anemic cat persistently infected with C. felis before, during and after A&A treatment. Cytauxzoon felis cytb genes were amplified and sequenced before, during and after A&A treatment.Results: Cytauxzoon felis was detected before, during and after A&A treatment including samples collected 570?days after treatment. After A&A treatment, the cat's anemia improved slightly. Cytb sequencing revealed only wild-type cytb methionine (M128) in samples collected before treatment. In samples collected after treatment, the cytb coded for isoleucine (M128I) and valine (M128I) at 2- and 4-months after treatment. These M128I and M128V mutations persisted even after a repeat treatment course with a higher dose atovaquone combined with the standard dose of azithromycin.Conclusions and clinical importance: This report documents C. felis atovaquone resistance associated with M128 cytb mutations. This study suggests parasites with mutations of cytb M128 can be selected and impart resistance to A&A treatment even with higher atovaquone dosing.
| S-EPMC7694809 | biostudies-literature
Project description:Cytauxzoonosis is an emerging infectious disease that affects wild felids as well as the domestic cat; it is caused by the apicomplexan protozoan parasites belonging to the genus Cytauxzoon. Cytauxzoonfelis is the species of major concern, whose transmission occurs via the bite of an infected tick. Cytauxzoonosis of the domestic cat has historically been considered uniformly fatal, with a short course of illness, and most domestic cats die within 9 to 15 days postinfection. However, increasing evidence of domestic cats surviving C. felis infection suggests the existence of different strains with various levels of pathogenicity. Although wild felids are considered natural reservoirs for this parasite, a number of studies suggest that domestic cats that have survived nonlethal infections may serve as an additional reservoir. The current article comprehensively reviews the parasite and its life cycle, geographic distribution, genetic variability, and pathogenesis, as well as host immunology and the diagnosis, treatment, and prevention of infection in the domestic cat. This information should provide a basis for better understanding the parasite as well as the pathogenesis of the disease.
| S-EPMC5608878 | biostudies-literature
Project description:We performed a molecular survey for Cytauxzoon felis infection in 311 domestic cats in Yunnan Province, China, in 2016 and found a prevalence of 21.5%. C. felis infection in domestic and wild cats in other provinces should be investigated to determine parasite prevalence and genetic diversity among cats throughout China.
| S-EPMC6346479 | biostudies-literature
Project description:Cytauxzoon felis is a hemoprotozoal tick-transmitted pathogen of felids. Felids that survive acute disease often remain infected and serve as reservoirs for subsequent tick transmission to other susceptible felines. States adjacent to Kansas have identified C. felis-domestic cat carriers while statewide awareness and concern of cytauxzoonosis have increased. The objective of this study was to determine the prevalence of C. felis-carriers in the eastern Kansas domestic cat population using a sensitive quantitative PCR assay targeting the C. felis Cox3 mitochondrial gene. An overall C. felis infection prevalence of 25.8% was determined for asymptomatic domestic cats in eastern Kansas. Significantly more C. felis-carrier cats were identified in spring and fall, suggesting a seasonal fluctuation of survivors. Additionally, a greater percentage of feral and owned cats were positive for C. felis compared to rescue/rescinded cats. This study demonstrates that C. felis-domestic cat carriers are common among cats that spend at least a portion of time outdoors in eastern Kansas, and that more cats likely survive cytauxzoonosis than expected. Understanding the role of domestic cat carriers of C. felis is essential in developing cytauxzoonosis mitigation strategies, including recommending year-round use of acaricide products for all cats that spend any time outdoors.
| S-EPMC7594093 | biostudies-literature
Project description:Cytauxzoon felis is a virulent, tick-transmitted, protozoan parasite that infects felines. Cytauxzoonosis was previously thought to be uniformly fatal in domestic cats. Treatment combining atovaquone and azithromycin (A&A) has been associated with survival rates of over 60%. Atovaquone, a ubiquinone analogue, targets C. felis cytochrome b (cytb), of which 30 unique genotypes have been identified. The C. felis cytb genotype cytb1 is associated with increased survival rates in cats treated with A&A. The purpose of this study was to design a PCR panel that could distinguish C. felis cytb1 from other cytochrome b genotypes. Primer pairs were designed to span five different nucleotide positions at which single-nucleotide polymorphisms in the C. felis cytb gene had been identified. Through the use of high-resolution melt analysis, this panel was predicted to distinguish cytb1 from other cytb genotypes. Assays were validated using samples from 69 cats with cytauxzoonosis for which the C. felis cytb genotypes had been characterized previously. The PCR panel identified C. felis cytb1 with 100% sensitivity and 98.2% specificity. High-resolution melt analysis can rapidly provide prognostic information for clients considering A&A treatment in cats with cytauxzoonosis.
| S-EPMC4508407 | biostudies-literature
Project description:Case series summaryA 5-month-old male intact domestic shorthair (DSH) cat (cat 1), a 1-year-old male neutered DSH cat (cat 2) and a 1.5-year-old female spayed DSH cat (cat 3) were submitted for gross necropsy after acute death, with the clinical suspicion of cytauxzoonosis. All three cats displayed signs of rapidly progressive clinical deterioration, including lethargy, anorexia, and hyper- or hypothermia. Cat 1 was euthanized owing to the grave prognosis for survival, whereas cats 2 and 3 were found dead 1–4 days after the onset of clinical signs. Remains were submitted to the Kansas State University Veterinary Diagnostic Laboratory for gross necropsy. In all three cats, general examination findings included icterus of the mucous membranes, multifocal pulmonary parenchymal hemorrhages, and splenic reddening and enlargement. Histologic examination revealed macrophages laden with protozoal schizonts diffusely distributed within blood vessels and vascular spaces of all affected organs, including the blood vessels of the uveal tract. The ciliary body within the anterior uveal tract was most affected.Relevance and novel informationThis is the first description of cytauxzoonosis affecting the eyes of infected cats. This report confirms involvement of ocular blood vessels similar to the classic lesions of the lungs, spleen and liver. In cats presenting with a history and clinical findings suggestive of cytauxzoonosis, complete ophthalmic examination is indicated to confirm or rule out ocular involvement.
| S-EPMC6293365 | biostudies-other
Project description:BackgroundCytauxzoon felis is a tick-transmitted apicomplexan that causes cytauxzoonosis in domestic cats (Felis catus). Even with intensive care, the mortality rate of acute cytauxzoonosis approaches 40% in domestic cats, while bobcats (Lynx rufus), the natural intermediate host of C. felis, remain clinically asymptomatic. However, multiple reports of domestic cats surviving acute disease without any treatment exist. One hypothesis for survival of these cats is infection with unique C. felis genotypes of lower pathogenicity. Prior studies have identified genetically distinct C. felis isolates containing polymorphisms within internal transcribed spacer regions (ITS) of the rRNA operon. However, these polymorphisms do not correlate with the clinical outcome of cytauxzoonosis, and so additional genetic markers are needed to test this hypothesis. We selected C. felis apical membrane antigen-1 (ama1) as a potential genetic marker of differential pathogenicity. AMA1 is a vaccine candidate for relatives of C. felis within Plasmodium spp.; however its historically high level of genetic polymorphism has resulted in escape from vaccine-induced immunity. While such diversity has hindered vaccine development, the expected polymorphism within the ama1 gene may be useful to evaluate population genetics.ResultsA 677 bp sequence of the C. felis ama1 gene was PCR-amplified from 84 domestic cats and 9 bobcats and demonstrated 99.9% sequence identity across all samples. A single nucleotide polymorphism (SNP) was identified in domestic cats and bobcats with evidence for co-infection with both genotypes identified in two domestic cats. The prevalence of the two genotypes varied with geographical distribution in domestic cats. Nucleotide diversity (π) and haplotype diversity (H) were calculated for C. felis ama1 and ama1 of related apicomplexans to assess genetic diversity. Based on these values (π = 0.00067 and H = 0.457), the diversity of the C. felis ama1 gene region analyzed is considerably lower than what is documented in related apicomplexans.ConclusionsIn surprising contrast to related apicomplexans, our results support that the sequence of the C. felis ama1 gene is highly conserved. While lack of genetic diversity limits utility of C. felis AMA1 as a genetic marker for clinical outcome, it supports further investigation as a vaccine candidate for cytauxzoonosis.
| S-EPMC6423858 | biostudies-literature
Project description:Cytauxzoon felis, a tick-borne hemoprotozoal pathogen of felids, causes an acute, often-fatal disease in domestic cats. While public awareness of the disease has increased, few studies have evaluated the incidence of acute cytauxzoonosis cases and their associated risk factors. The objective of this study was to retrospectively review records of cats diagnosed with acute cytauxzoonosis in eastern Kansas from 2006-2019 using clinic records and determine: (i) feline cytauxzoonosis risk factors; and (ii) if cytauxzoonosis case incidence is increasing. Although inter-annual variation of acute cytauxzoonosis diagnosis was observed in the eastern Kansas domestic cat population, the overall incidence trend remained largely unchanged over the 14-year case review period. In comparison to ill (C. felis-unrelated) control cases, more acute cytauxzoonosis cases were diagnosed in spring and summer, suggesting a seasonal fluctuation of infection, with samples most commonly submitted from ?1 year old, owned, male cats. Although cytauxzoonosis case submissions remained consistent over the broad study period, increasing tick vector and domestic cat reservoir populations may contribute to additional cytauxzoonosis case expansion in endemic areas. Investigating the incidence of acute cytauxzoonosis, patient risk factors, and ecological variables that influence disease transmission are important steps towards developing and communicating the need for effective cytauxzoonosis control strategies for high-risk cat populations.
| S-EPMC7767035 | biostudies-literature
Project description:BackgroundCytauxzoonosis is a disease of felids in North America caused by the tick-transmitted apicomplexan parasite Cytauxzoon felis. Cytauxzoonosis is particularly virulent for domestic cats, but no vaccine currently exists. The parasite cannot be cultivated in vitro, presenting a significant limitation for vaccine development.MethodsRecent sequencing of the C. felis genome has identified over 4300 putative protein-encoding genes. From this pool we constructed a protein microarray containing 673 putative C. felis proteins. This microarray was probed with sera from C. felis-infected and naïve cats to identify differentially reactive antigens which were incorporated into two expression library vaccines, one polyvalent and one monovalent. We assessed the efficacy of these vaccines to prevent of infection and/or disease in a tick-challenge model.ResultsProbing of the protein microarray resulted in identification of 30 differentially reactive C. felis antigens that were incorporated into the two expression library vaccines. However, expression library immunization failed to prevent infection or disease in cats challenged with C. felis.ConclusionsProtein microarray facilitated high-throughput identification of novel antigens, substantially increasing the pool of characterized C. felis antigens. These antigens should be considered for development of C. felis vaccines, diagnostics, and therapeutics.
| S-EPMC6310948 | biostudies-literature
Project description:The glaucomas are a group of diseases characterized by optic nerve damage that together represent a leading cause of blindness in the human population and in domestic animals. Here we report a mutation in LTBP2 that causes primary congenital glaucoma (PCG) in domestic cats. We identified a spontaneous form of PCG in cats and established a breeding colony segregating for PCG consistent with fully penetrant, autosomal recessive inheritance of the trait. Elevated intraocular pressure, globe enlargement and elongated ciliary processes were consistently observed in all affected cats by 8 weeks of age. Varying degrees of optic nerve damage resulted by 6 months of age. Although subtle lens zonular instability was a common feature in this cohort, pronounced ectopia lentis was identified in less than 10% of cats examined. Thus, glaucoma in this pedigree is attributed to histologically confirmed arrest in the early post-natal development of the aqueous humor outflow pathways in the anterior segment of the eyes of affected animals. Using a candidate gene approach, significant linage was established on cat chromosome B3 (LOD 18.38, q = 0.00) using tightly linked short tandem repeat (STR) loci to the candidate gene, LTBP2. A 4 base-pair insertion was identified in exon 8 of LTBP2 in affected individuals that generates a frame shift that completely alters the downstream open reading frame and eliminates functional domains. Thus, we describe the first spontaneous and highly penetrant non-rodent model of PCG, identifying a valuable animal model for primary glaucoma that closely resembles the human disease providing valuable insights into mechanisms underlying the disease and a valuable animal model for testing therapies.
2016-05-01 | GSE73263 | GEO