Dataset Information

Cytauxzoon felis cytochrome b gene mutation associated with atovaquone and azithromycin treatment.

ABSTRACT: 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.

SUBMITTER: Hartley AN

PROVIDER: S-EPMC7694809 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Cytauxzoon felis cytochrome b gene mutation associated with atovaquone and azithromycin treatment.

Hartley Ashley N AN Marr Henry S HS Birkenheuer Adam J AJ

Journal of veterinary internal medicine 20201104 6

<h4>Background</h4>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.<h4>Objective</h4>To serially characterize the C. felis cytb sequences from a cat that remained persistently infected after A&A treatment.<h4>Animal</h4>A cat with naturally occurring C. felis infection.<h4>Methods</h4>C ...[more]

PMID: 33146909

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Project description:Cytauxzoon felis is a tick-borne hemoprotozoan parasite that causes life-threatening disease in domestic cats in the United States. Currently, the platforms for C. felis research are limited to natural or experimental infection of domestic cats. This study aims to develop an alternative model by infecting Amblyomma americanum ticks with C. felis via direct injection. Amblyomma americanum adults were injected with C. felis-infected feline erythrocytes through two routes: directly into the digestive tract through the anal pore (IA injection), or percutaneously into the tick hemocoel (IH injection). RNAscope® in situ hybridization (ISH) was used to visualize the parasites within the ticks at different time points after injection. Four months after injection, ticks were divided into 3 infestation groups based on injection methods and inoculum type and fed on 3 naïve cats to assess the ticks' ability to transmit C. felis. Prior to the transmission challenge, selected ticks from each infestation group were tested for C. felis RNA via reverse transcription-PCR (RT-PCR). In both IA- and IH-injected ticks, ISH signals were observed in ticks up to 3 weeks after injection. The number of hybridization signals notably decreased over time, and no signals were detected by 4 months after injection. Prior to the transmission challenge, 37-57% of the sampled ticks were positive for C. felis RNA via RT-PCR. While the majority of injected ticks successfully attached and fed to repletion on all 3 cats during the transmission challenge, none of the cats became infected with C. felis. These results suggest that injected C. felis remained alive in ticks but was unable to progress to infective sporozoites after injection. It is unclear why this infection technique had been successful for other closely related tick-borne hemoprotozoa and not for C. felis. This outcome may be associated with uncharacterized differences in the C. felis life cycle, the lack of the feeding or molting in our model or absence of gametocytes in the inoculum. Nonetheless, our study demonstrated the potential of using ticks as an alternative model to study C. felis. Future improvement of a tick model for C. felis should consider other tick species for the injection model or utilize infection methods that more closely emulate the natural infection process.

Dataset Information

Cytauxzoon felis cytochrome b gene mutation associated with atovaquone and azithromycin treatment.

Publications

Cytauxzoon felis cytochrome b gene mutation associated with atovaquone and azithromycin treatment.

Similar Datasets

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