Cytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle
Abstract
Human babesiosis is an emerging tick-borne malaria-like illness caused by Babesia parasites following their development in erythrocytes. Here, we show that a mutation in the Babesia microti mitochondrial cytochrome b (Cytb) that confers resistance to the antibabesial drug ELQ-502 decreases parasite fitness in the arthropod vector. Interestingly, whereas the mutant allele does not affect B. microti fitness during the mammalian blood phase of the parasite life cycle and is genetically stable as parasite burden increases, ELQ-502–resistant mutant parasites developing in the tick vector are genetically unstable with a high rate of the wild-type allele emerging during the nymphal stage. Furthermore, we show that B. microti parasites with this mutation are transmitted from the tick to the host, raising the possibility that the frequency of Cytb resistance mutations may be decreased by passage through the tick vector, but could persist in the environment if present when ticks feed.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 17, 2021
- Source ID
- 10.1093/infdis/jiab321
Entities
People
- Anasuya C. Pal
- Choukri Ben Mamoun
- Isaline Renard
- J Stone Doggett
- Joy E. Chiu
- Michael K. Riscoe
- P. Holland Alday
- Santosh George
- Sukanya Narasimhan
Organizations
- National Institutes of Health
- Steven & Alexandra Cohen Foundation
- United States Department of Defense
- United States Department of Veterans Affairs
- Veterans Affairs Medical Center (Oregon)
- Yale University