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macro- (global) epidemiologic questions
(21)
. Direct comparison against the
current gold standard, MLST analysis, suggests that
spa
typing is predictive
of the
S. aureus
genotype, and its resolution approaches the discrimination of
PFGE
(21,30,31,32,33)
.
Although the exact biological function of protein A is not well understood,
there are no examples in the literature of a naturally occurring protein A-
negative
S. aureus
strain. While the inactivation of protein A does not appear
to affect the strain's “fitness,” it is noteworthy that as a result of their in-
frame organization, the size and content of the repeat units appear to have
biological restrictions. Among the non-synonymous changes, the overall amino
acid composition of the repeat region appears to be maintained, suggesting
that the substitutions are not under strong selective pressures (
see
Fig. 2
).
This observation is further supported by the d
S
/d
N
value, which is the ratio of
the number of synonymous substitutions per potential synonymous site to the
number of non-synonymous substitutions per potential non-synonymous site.
Analysis of 38
spa
repeats showed a d
S
/d
N
value of 6.4, where a ratio of <1
indicates positive selection pressure, a value of 1 indicates neutral evolution,
Fig. 2. Sequence content of
spa
repeats at nucleotide and amino acid levels.
Repeats differing at the nucleotide level may be identical at the amino acid level.
Identical codons are depicted using the same colors; equivalent codons corresponding
to synonymous mutations are colored with similar hues. The translated sequence reveals
a conserved octapeptide motif comprised almost exclusively of charged amino acids
and is suggestive of a surface-exposed loop region with repeating turns. Repeats T1-Z1
bear a single codon insertion between positions 1 and 2; most common
spa
types begin
with one of these repeats, such that the initial repeat is usually 27-bp in length (vs.
24-bp).
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