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are both temporally and geographically restricted
(22)
. In these settings, the
primary objective is to identify common strains that are spreading within a larger
population (i.e., clonal spread) of unrelated isolates; consequently, the degree
of polymorphism among temporally restricted outbreak strains is expected to
be small. A number of studies have confirmed the validity and utility of
spa
typing for local epidemiological investigations
(23,24,25,26)
. However, as
spa
typing is a single-locus genotyping method, it was not clear whether it would be
amenable to long-term or global epidemiologic studies, such as understanding
the relatedness of strains isolated from distal regions, the nature and extent of
genetic variation within the species, and the phylogenetic relationships among
all strains
(21)
. In other words, a single-locus target may not accurately reflect
the relationships between distantly related isolates that have had substantial
time to diversify due to convergence and/or recombination events.
Staphylococcus aureus
is a heterogenous (polymorphic) species that was
recently reported to possess a clonal population structure
(27,28)
. It is thought
that this species diversifies largely by point mutations rather than undergoing
extensive recombination or horizontal transfer and displays a high degree
of linkage disequilibrium (non-random associations between genetic loci).
Therefore, to study global epidemiology and population genetics, a highly
discriminating marker that accumulates genetic variation relatively slowly is
required. Typically, multilocus enzyme electrophoresis (MLEE) is used to
discern amino acid changes in metabolic enzymes
(29)
; more recently, MLST,
an analogous method that compares sequence variation in numerous house-
keeping gene targets is used for such studies
(5)
. However, a single-locus
DNA sequence-based method that can simultaneously index micro- and macro-
variation by two independent mechanisms would offer a rapid and cost-effective
alternative.
A recent study reexamined a collection of 36 strains previously characterized
by DNA microarray analysis based on 90% of the annotated genome of the COL
strain
(21,28)
. Isolates were selected to be representative of the most abundant
lineages derived from over 2000 spatio-temporally diverse isolates shown by
MLEE to provide a likely population structure of
S. aureus
. The strains were
genotyped by sequencing VNTRs in
coa
and
spa
, as well as by PFGE analysis,
and the extent of genetic clustering was compared to the phylogenetic structure
generated by MLEE and DNA microarray data. The results revealed
spa
typing
to be highly discriminating in grouping strains based on sequence changes in
the repeat region, which appears to have a clock-speed in register with the
overall evolutionary clock of this species. That is, point mutations occur at
a lower rate (clock speed) than repeat number variation, and therefore, the
dual dynamics of slow point mutations in combination with faster changes
in repeat number enable
spa
typing to be used for both micro- (local) and
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