Strain Composition of the EhrlichiaAnaplasma marginalewithin Persistently Infected Cattle, a Mammalian Reservoir for Tick Transmission

Abstract

Tick-borne ehrlichial pathogens of animals and humans require a mammalian reservoir of infection from which ticks acquire the organism for subsequent transmission. In the present study, we examined the strain structure of Anaplasma marginale, a genogroup II ehrlichial pathogen, in both an acute outbreak and in persistently infected cattle that serve as a reservoir for tick transmission. Using the msp1␣ genotype as a stable strain marker, only a single genotype was detected in a disease outbreak in a previously uninfected herd. In contrast, a diverse set of genotypes was detected in a persistently infected reservoir herd within a region where A. marginale is endemic. Genotypic diversity did not appear to be rapidly generated within an individual animal, because only a single genotype, identical to that of the inoculating strain, was detected at time points up to 2 years after experimental infection, and only a single identical genotype was found in repeat sampling of individual naturally infected cattle. Similarly, only a single genotype, identical to that of the experimentally inoculated St. Maries or South Idaho strain, was identified in the bloodmeal taken by Dermacentor andersoni ticks, in the midgut and salivary glands of the infected ticks, and in the blood of acutely infected cattle following tick transmission. The results show that mammalian reservoirs harbor genetically heterogeneous A. marginale and suggest that different genotypes are maintained by transmission within the reservoir population.

Superinfection as a driver of genomic diversification in antigenically variant pathogens

“…Strain A, which encodes the same allelic variant repertoire as the endemic strain, is not able to establish infection in the population because of the presence of existing immunity against a broad array of the shared antigenic variants. This strain A model is supported by studies within endemic regions where A. marginale strains encoding the same allelic msp2 repertoire do not superinfect (20,21). In contrast, strain B, which encodes a different set of alleles, can evade preexisting immunity and establish infection within the population as the proportion of strain B-susceptible animals is large.…”

“…In contrast, strain B (yellow circles), encoding a unique variant repertoire, will establish infection in the population as the existing persistently infected animals also represent a susceptible population and transmission results in strain superinfection (green circles). The assumptions of the model regarding infection prevalence within endemic regions, equal quantitative transmissibility of strains, and the resistance to superinfection of genetically similar strains are based on both field and experimental studies of A. marginale transmission (20,21,26).…”

Complete genome sequencing of Anaplasma marginale reveals that the surface is skewed to two superfamilies of outer membrane proteins

“…Msp1␣ is a single copy gene and exhibits strain differences caused by a variable number and sequence of tandem repeats units of 86-89 bp in length (47). These repeats have been designated by letters, and the St. Maries strain msp1␣ contains three repeats with the designation JBB (47). Interestingly, MSP1a has no canonical signal peptide, although it has been demonstrated to be surface exposed (48).…”

“…MSP1 is a surface exposed heteromeric complex consisting of MSP1a and MSP1b. Msp1␣ is a single copy gene and exhibits strain differences caused by a variable number and sequence of tandem repeats units of 86-89 bp in length (47). These repeats have been designated by letters, and the St. Maries strain msp1␣ contains three repeats with the designation JBB (47).…”

Anaplasma marginale msp1 α Genotypes Evolved under Positive Selection Pressure but Are Not Markers for Geographic Isolates

“…However, recent data support the existence of genetic heterogeneity in the structures of the msp1␣ sequences of isolates recovered from infected animals within a state (9) and even in a single herd of cattle in an area of endemicity (23), thus questioning the use of msp1␣ sequences to identify geographic isolates of A. marginale. Although single msp1␣ genotypes have been identified in individual cattle that were naturally or experimentally infected and sampled at different stages of infection (4,23), a finding that we demonstrated could be explained by infection exclusion of A. marginale isolates in infected cattle (10), these findings suggest a rapid evolution of msp1␣ sequences, resulting in the maintenance of A. marginale genotypes in the population through different transmission events (9,10,23).…”