Independence ofAnaplasma marginaleStrains with High and Low Transmission Efficiencies in the Tick Vector following Simultaneous Acquisition by Feeding on a Superinfected Mammalian Reservoir Host

Abstract

Strain superinfection occurs when a second pathogen strain infects a host already carrying a primary strain. Anaplasma marginale superinfection occurs when the second strain carries a variant repertoire different from that of the primary strain, and the epidemiologic consequences depend on the relative efficiencies of tick-borne transmission of the two strains. Following strain superinfection in the reservoir host, we tested whether the presence of two A. marginale (sensu lato) strains that differed in transmission efficiency altered the transmission phenotypes in comparison to those for single-strain infections. Dermacentor andersoni ticks were fed on animals superinfected with the Anaplasma marginale subsp. centrale vaccine strain (low transmission efficiency) and the A. marginale St. Maries strain (high transmission efficiency). Within ticks that acquired both strains, the St. Maries strain had a competitive advantage and replicated to significantly higher levels than the vaccine strain. The St. Maries strain was subsequently transmitted to naïve hosts by ticks previously fed either on superinfected animals or on animals singly infected with the St. Maries strain, consistent with the predicted transmission phenotype of this strain and the lack of interference due to the presence of a competing low-efficiency strain. The vaccine strain was not transmitted by either singly infected or coinfected ticks, consistent with the predicted transmission phenotype and the lack of enhancement due to the presence of a high-efficiency strain. These results support the idea that the strain predominance in regions of endemicity is mediated by the intrinsic transmission efficiency of specific strains regardless of occurrence of superinfection.Strain superinfection occurs when a second pathogen strain infects a host already persistently infected with a primary strain. Superinfection has epidemiologic and pathogenic relevance for pathogens ranging from small-genome RNA viruses, such as human immunodeficiency virus and hepatitis C virus, to complex parasites, such as Trypanosoma brucei (1,10,12,20,24,37). The epidemiologic consequences of superinfection depend on the subsequent fitness of the two strains for onward transmission to a new host. We address this question by studying transmission of Anaplasma marginale, a tick-borne bacterial pathogen which establishes persistent infection in mammalian reservoir hosts (domestic and wild ruminants) (21) and for which the basis for strain superinfection has recently been reported (8).A. marginale strain superinfection occurs when the second strain carries a repertoire of the antigenically variable outer membrane protein (designated major surface protein-2 [Msp2]) different from that of the primary strain, allowing the second strain to escape the immune response generated against the primary strain (8, 25). Once superinfection is established, both strains are maintained in the host, which serves as the reservoir for subsequent tick acquisition and transmission (18). Whether and how patho...

Expansion of Variant Diversity Associated with a High Prevalence of Pathogen Strain Superinfection under Conditions of Natural Transmission

“…This conclusion is supported by progressive analysis of variant composition: (i) animals with naturally acquired superinfection had a statistically significantly greater number of unique Msp2 sequences than animals either experimentally infected with single strains or infected with a single strain naturally, (ii) the greater number of unique sequences reflected a statistically significant increase in primary structural diversity in the superinfected animals, and (iii) the increase in primary structural diversity reflected increased combinations of the newly identified hypervariable microdomains. These findings under conditions of natural transmission are consistent with those from previous experimental studies in which A. marginale strain superinfection was established when the second strain differed in its msp2 allelic repertoire compared to the primary strain and the unique alleles were expressed by the second strain at the time of superinfection (16,18). The ability to detect all donor alleles and an oligoclonal repertoire of expressed variants using strains for which the complete allelic repertoire has been sequenced provides confidence that the technical approach captured the Msp2 diversity in the experimental infections.…”

Association of Pathogen Strain-Specific Gene Transcription and Transmission Efficiency Phenotype of Anaplasma marginale

“…A. marginale subsp. centrale (the Israel vaccine strain) is unique among the A. marginale strains described to date in that it colonizes the tick midgut and salivary gland but replicates at a significantly lower level in the salivary gland (9,25). The numbers of organisms in the salivary gland and saliva at the time of transmission are 10-fold and 30-fold less, respectively, than the numbers of organisms in a high-transmission-efficiency strain (25).…”

“…The numbers of organisms in the salivary gland and saliva at the time of transmission are 10-fold and 30-fold less, respectively, than the numbers of organisms in a high-transmission-efficiency strain (25). Transmission is correspondingly less efficient and requires Ͼ30-fold more ticks (9,25). This statistically and biologically significant transmission phenotype provides a model for linking gene content and expression with transmission efficiency.…”

Anaplasma marginale Superinfection Attributable to Pathogen Strains with Distinct Genomic Backgrounds

“…Genomic comparison of multiple strains revealed that although A. marginale has a "closed core" genome with essentially the same gene content among all strains, the repertoire of msp2 alleles is distinct (17,18). Importantly, strains with a distinct msp2 allelic repertoire have been shown experimentally to be capable of strain superinfection, in which a second strain establishes infection in an animal already infected with a primary strain (15,19,20). Superinfection requires that the second strain contain at least one unique msp2 allele and that this be expressed at superinfection (19,21).…”