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Antigenic variation of Anaplasma marginale by expression of MSP2 mosaics
1Department of Pathobiology, College of Veterinary Medicine, University of Florida, Gainesville, Florida 32611-0880, USA. barbeta@mail.vetmed.ufl.edu
Abstract:
Anaplasma marginale is a tick-borne pathogen, one of several closely related ehrlichial organisms that cause disease in animals and humans. These Ehrlichia species have complex life cycles that require, in addition to replication and development within the tick vector, evasion of the immune system in order to persist in the mammalian reservoir host. This complexity requires efficient use of the small ehrlichial genome. A. marginale and related ehrlichiae express immunoprotective, variable outer membrane proteins that have similar structures and are encoded by polymorphic multigene families. We show here that the major outer membrane protein of A. marginale, MSP2, is encoded on a polycistronic mRNA. The genomic expression site for this mRNA is polymorphic and encodes numerous amino acid sequence variants in bloodstream populations of A. marginale. A potential mechanism for persistence is segmental gene conversion of the expression site to link hypervariable msp2 sequences to the promoter and polycistron.
Insights
Anaplasma marginale, a tick-borne pathogen, uses a polycistronic mRNA to express variable outer membrane proteins (MSPs). Gene conversion may allow it to evade the host immune system for persistence.
Area of Science:
- Microbiology
- Immunology
- Veterinary Science
Background:
- Anaplasma marginale is a tick-borne pathogen causing disease in animals and humans.
- Ehrlichial organisms like A. marginale have complex life cycles involving tick vectors and mammalian hosts.
- Persistence in hosts requires immune system evasion, necessitating efficient genome utilization.
Purpose of the Study:
- To investigate the gene expression mechanism of the major outer membrane protein (MSP2) in Anaplasma marginale.
- To understand how A. marginale generates sequence diversity in MSP2 for immune evasion.
- To explore potential mechanisms for A. marginale persistence in mammalian hosts.
Main Methods:
- Analysis of the polycistronic mRNA encoding MSP2.
- Characterization of the polymorphic genomic expression site for MSP2.
- Investigation of sequence variation in MSP2 within A. marginale populations.
Main Results:
- MSP2 of A. marginale is encoded on a polycistronic mRNA.
- The genomic expression site for this mRNA is polymorphic, encoding numerous amino acid variants.
- Segmental gene conversion is proposed as a mechanism for linking hypervariable msp2 sequences to the promoter.
Conclusions:
- A. marginale utilizes a polycistronic mRNA for MSP2 expression.
- Genomic polymorphism and gene conversion are likely mechanisms for generating MSP2 diversity.
- These mechanisms contribute to immune evasion and persistence of A. marginale in reservoir hosts.