Abstract:
:Anaplasma marginale subsp. centrale was the first vaccine used to protect against a rickettsial disease and is still in widespread use a century later. As its use preceded development of either cryopreservation or cell culture, the vaccine strain was maintained for decades by sequential passage among donor animals, excluding the natural tick-borne transmission cycle that provides a selective pressure or population "bottleneck." We demonstrated that the vaccine strain is genetically heterogeneous at 46 chromosomal loci and that heterogeneity was maintained upon inoculation into recipient animals. The number of variants per site ranged from 2 to 11 with a mean of 2.8/locus and a mode and median of 2/locus; variants included single-nucleotide polymorphisms, insertions/deletions, polynucleotide tracts, and different numbers of perfect repeats. The genetic heterogeneity is highly unlikely to be a result of strain contamination based on analysis using a panel of eight gene markers with a high power for strain discrimination. In contrast, heterogeneity appears to be a result of genetic drift in the absence of the restriction of tick passage. Heterogeneity could be reduced following tick passage, and the reduced heterogeneity could be maintained in sequential intravenous and tick-borne passages. The reduction in vaccine strain heterogeneity following tick passage did not confer an enhanced transmission phenotype, indicating that a stochastically determined population bottleneck was likely responsible as opposed to a positive selective pressure. These findings demonstrate the plasticity of an otherwise highly constrained genome and highlight the role of natural transmission cycles in shaping and maintaining the bacterial genome.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Herndon DR,Ueti MW,Reif KE,Noh SM,Brayton KA,Agnes JT,Palmer GHdoi
10.1128/IAI.00199-13subject
Has Abstractpub_date
2013-05-01 00:00:00pages
1852-8issue
5eissn
0019-9567issn
1098-5522pii
IAI.00199-13journal_volume
81pub_type
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journal_title:Infection and immunity
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