EUKARYOTIC CELL, Apr. 2010, p. 619–625
Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Vol. 9, No. 4
Multilocus Sequence Type Analysis Reveals both Clonality and
Recombination in Populations of Candida glabrata Bloodstream
Isolates from U.S. Surveillance Studies?†
Timothy J. Lott, Joa ˜o P. Frade, and Shawn R. Lockhart*
Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
Received 5 January 2010/Accepted 21 February 2010
The human commensal yeast Candida glabrata is becoming increasingly important as an agent of nosocomial
bloodstream infection. However, relatively little is known concerning the genetics and population structure of
this species. We have analyzed 230 incident bloodstream isolates from previous and current population-based
surveillance studies by using multilocus sequence typing (MLST). Our results show that in the U.S. cities of
Atlanta, GA; Baltimore, MD; and San Francisco, CA during three time periods spanning 1992 to 2009, five
populations of C. glabrata bloodstream isolates are defined by a relatively small number of sequence types.
There is little genetic differentiation in the different C. glabrata populations. We also show that there has been
a significant temporal shift in the prevalence of one major subtype in Atlanta. Our results support the concept
that both recombination and clonality play a role in the population structure of this species.
In the most recently available survey of nosocomial blood-
stream infections, Candida species were the fourth most com-
mon organism, surpassed only by Staphylococcus and Entero-
coccus species (24). Although Candida albicans remains the
most commonly isolated Candida species worldwide, the inci-
dence of Candida glabrata infection has been increasing
steadily so that it is now the second most common cause of
Candida infection in the United States (14). C. glabrata is
considered a normal component of the human epithelial flora
but is capable of causing serious systemic infections in suscep-
tible hosts. This increase in the relative proportion of infec-
tions due to C. glabrata has come during the period of the
introduction and prophylactic use of azole antifungal drugs
(21) and may be a reflection of the decreased susceptibility of
C. glabrata to these azole antifungal drugs (7, 15). Many ques-
tions regarding the epidemiology of C. glabrata infections have
a direct impact on public health and still remain unanswered.
Is the decreased susceptibility due to a small number of clones
expanding in a population, or are all isolates capable of devel-
oping resistance to azole drugs? Are some isolates more viru-
lent than others and therefore more prevalent in a population?
Can we monitor the expansion of clonal isolates that may be
more virulent or have increased drug resistance? A better
understanding of the population genetics of C. glabrata may
allow us to answer some of these questions.
Many DNA fingerprinting methods have been developed for
the investigation of the population genetics of Candida species
(19). Two of the most important aspects of a typing system are
reproducibility between laboratories and the ability to archive
strain types. Multilocus sequence typing (MLST) has been
developed as a typing system which allows highly reproducible
strain discrimination as well as the development of genotypic
strain archives that can be stored digitally for both prospective
and retrospective analysis of isolates (13, 22). An MLST system
which utilizes six housekeeping genes on six separate chromo-
somes was developed for C. glabrata (4), and an online archive
of sequence types (STs) was established (http://cglabrata.mlst
.net). Several studies utilizing this typing system have described
the molecular population structure of both regional and world-
wide collections of C. glabrata isolates (4, 5, 11, 12).
During the past 2 decades, the Centers for Disease Control
and Prevention (CDC) and our partners have undertaken
three active, population-based surveillance studies in order to
determine the incidence of candidemia, the distribution of
species causing bloodstream infection, and the prevalence of
antifungal drug resistance (8, 10). In each case, two major
metropolitan areas were included: San Francisco, CA, and
Atlanta, GA (1992 to 1993); Baltimore, MD, and the state of
Connecticut (1998 to 2000); and Atlanta, GA, and Baltimore,
MD (2008 to 2010). Population-based surveillance is unique in
that it includes the total population of a particular geographic
area and avoids the biases associated with single or select
institutional studies. During each of the surveillance studies,
incident bloodstream isolates from all hospitals within each
defined geographic area were collected and identified to the
species level. While C. glabrata isolates comprised a smaller
percentage of the isolates in the 1992-to-1993 and 1998-to-
2000 surveillance studies (8, 10), they represent almost a third
of the isolates collected during the current surveillance (N.
Iqbal and S. Lockhart, unpublished observations).
In the present work, we have characterized by MLST anal-
ysis 230 isolates of C. glabrata from five populations (excluding
Connecticut) separated both geographically and temporally.
This unique collection of isolates allowed an analysis of the
changing population genetics of this organism. We identified
31 unique STs and showed the maintenance of a major ST both
geographically and temporally that is unique to the United
* Corresponding author. Mailing address: Mycotic Diseases Branch,
Centers for Disease Control and Prevention, 1600 Clifton Rd., Mail-
stop G-11, Atlanta, GA 30333. Phone: (404) 639-2569. Fax: (404)
639-3546. E-mail: firstname.lastname@example.org.
† Supplemental material for this article may be found at http://ec
?Published ahead of print on 26 February 2010.
States. An analysis of the relatedness of specific C. glabrata
populations and a strong indication for recombination within
and between populations are provided.
MATERIALS AND METHODS
Isolates. A total of 230 available incident C. glabrata bloodstream isolates from
two previous population-based surveillance studies of metropolitan Atlanta, GA;
Baltimore City and County, MD; and metropolitan San Francisco, CA (8, 10)
and from an ongoing, population-based surveillance in metropolitan Atlanta and
Baltimore City and County (2) were used in this study. For San Francisco and
Atlanta from 1992 to 1993, all of the available isolates from each city were
surveyed, comprising 64% of all cases of C. glabrata detected in that surveillance.
For Baltimore from 1998 to 2000, 50 isolates were randomly chosen from 168
available, representing approximately 18% of all cases of C. glabrata detected
during the surveillance. For Atlanta and Baltimore in 2008, all of the available
isolates were chosen from Atlanta and Baltimore until more than 50 isolates
from each population had been surveyed. A complete listing of strains and STs
are given in Table S1 in the supplemental material.
Prior to use, all isolates were stored in glycerol at ?70°C. Isolates were
identified as C. glabrata by conventional biochemical means and by Luminex
assay (K. Etienne and S. A. Balajee, submitted for publication) and were con-
firmed by positive MLST results. The closely related species Candida nivariensis
and Candida bracarensis were ruled out because type isolates of these species
could not be amplified with the C. glabrata MLST primer set.
DNA extraction, PCR amplification, and sequencing. After passage of each
isolate twice on Sabouraud dextrose agar plates, DNA was extracted using the
Mo Bio microbial DNA isolation kit (Mo Bio Laboratories, Inc., Carlsbad, CA)
according to the manufacturer’s instructions. The oligonucleotide primers used
for MLST analysis were those described by Dodgson and coworkers (4). PCRs
were performed in a 25-?l volume containing 10 ng of genomic DNA, 0.2 ?M
each primer, Roche Taq DNA polymerase, and Taq PCR master mix as de-
scribed by the manufacturer (Roche Diagnostics, Indianapolis, IN). Reaction
conditions were as previously described for each individual primer set (4). PCR
products were purified using ExoSap-It as described by the manufacturer (USB,
Cleveland, OH). Sequencing reactions were performed using BigDye terminator
technology (ABI, Foster City, CA) with an ABI Prism 3730 DNA sequencer. All
loci were sequenced in both forward and reverse directions with the same
primers as those used for the PCRs.
Data analysis. Nucleotide sequences were determined by alignment of forward
and reverse sequences by using Sequencher 4.7 software (Genecodes Inc., Ann
Arbor, MI), and polymorphisms were confirmed by visual examination of the
sequence traces. Sequences were then compared to the C. glabrata MLST data-
base (http://cglabrata.mlst.net) to assign allele numbers and STs.
Population genetic analysis. For population analysis, alleles for each strain
were assigned alphabetic equivalents, and strains were grouped by populations
and analyzed by Popgene v1.3 (http://www.ualberta.ca/?fyeh/index.htm) under
the criteria of haploid, codominant markers. Wright’s fixation index (FST) values
were calculated using the formula FST? Ht ? Hs/Ht (23), and using values of
Hs and Ht from Nei’s analysis of gene diversity. FSTvalues of ?0.05 generally
indicate little interpopulation variance, and can range from 0 for identical pop-
ulations to 1 for populations sharing no alleles in common (9). Values of genetic
identity and distance used Nei’s unbiased measurements (17). Nei’s unbiased
genetic pairwise identity value calculates genetic diversity between populations
across all loci simultaneously, with the assumption that differences arise due to
both mutation and genetic drift. Distance values are given on a logarithmic scale,
where values approaching 1 indicate complete divergence and negative numbers
indicate no divergence. The likelihood-based tree was generated using a neigh-
bor-joining algorithm in the HyPhy software package (16). Bootstrap values were
calculated using the Mega 4.1 software package (20). The population-based trees
were constructed using PHYLIP 3.5 (6). The Index of Association (IA) and
rBarD were calculated using Multilocus 1.3b (1). Two-locus linkage disequilib-
rium (LD) was calculated using POPGENE v1.3 (http://www.ualberta.ca/?fyeh).
General attributes of population profiles as determined by
MLST. A total of 230 incident bloodstream isolates from pop-
ulation-based surveillance in the United States were typed
using MLST. Five populations of isolates were analyzed. Pop-
ulation 1 consisted of 38 isolates collected in San Francisco
from 1992 to 1993; population 2 consisted of 26 isolates col-
lected in the metro Atlanta area from 1992 to 1993 from 25
hospitals; population 3 consisted of 50 isolates collected in
Baltimore City and County from 1998 to 2000 from 14 hospi-
tals; population 4 consisted of 63 isolates collected in metro
Atlanta in 2008 from 25 hospitals; population 5 consisted of 53
isolates collected in Baltimore City and County in 2008 from 15
hospitals. The six sequenced loci resulted in 3,345 combined
base pairs. All of the analyzed nucleotides were within open
reading frames, so no insertions or deletions were expected or
detected. We observed no indications of heterozygosity for any
of the six loci in any of the strains. A total of 127 nucleotide
sites (3.8%) across all six genes combined were found to be
polymorphic. For six isolates, STs were comprised of new com-
binations of previously identified alleles (4). One isolate in the
1998 Baltimore collection (CAS99-0115) was found to have
both a new mutation and a different combination of polymor-
phisms in the NMT1 locus. This new mutation consisted of a
T3C second position nonsynonymous transition (Ile3Thr) at
nucleotide position 872. For the TRP1 locus, there were new
combinations of previously described polymorphisms and a
new mutation, an A3T second position nonsynonymous trans-
version (Asp3Val) at nucleotide position 427. For all popu-
lations, the most informative site was NMT1, with 18 alleles in
the total collection, and the least informative site was UGP1,
with only seven alleles.
MLST analysis resulted in the delineation of 31 STs from
these 230 isolates. Sixteen (52%) of the STs were represented
by single isolates, but this number represents only 7% of the
total number of isolates. The most diverse population was that
from Baltimore from 1998 to 2000, with 17 STs, and the pop-
ulation with the lowest ratio of STs to isolates was that from
Atlanta from 1992 to 1993, with one unique ST for every 2.4
isolates genotyped (Table 1).
We observed eight new STs that were not in the C. glabrata
MLST database. One strain from the 1998 Baltimore collec-
tion, CAS99-0437, contained new alleles in five of the six loci,
FKS1, NMT1, TRP1, UGP1, and URA3. In all but the TRP1
locus, the new alleles were derived from new combinations of
previously characterized polymorphisms.
STs 16, 19, and 3 were the most abundant, and each ap-
peared in all five of the study populations. These three STs
TABLE 1. Ratio of unique STs to the number of isolates in
subdivided populations and percentage of population in
the three major STs
No. of isolates (%)
38111:3.51 (3)10 (26)6 (16)
26111:2.41 (4)4 (15)5 (19)
5017 1:2.96 (12)8 (16) 7 (14)
aRatio of the number of STs to the number of isolates.
620LOTT ET AL.EUKARYOT. CELL
together represented 51% of the entire study population. They
represented 38% and 83% of the isolates from the 1992-to-
1993 and 2008 Atlanta populations, respectively; 42% and 41%
of the isolates from the 1998-to-2000 and 2008 Baltimore pop-
ulations, respectively; and 45% of the isolates from the 1992-
to-1993 San Francisco population (Table 1). Neighbor-joining
trees were constructed for each population based on the con-
catenated sequences of the given genotypes (clone corrected)
and are shown in Fig. 1. The frequencies of the corresponding
STs are indicated by the diameters of the terminal circles. It
can be seen that the overall topologies are similar, with the
possible exception of the Georgia 2008 population (Fig. 1B). In
this case, the tree topology is more polarized due to the inclu-
sion of STs 80, 81, and 82, which are newly described in this
study and are unique to that population.
Temporal changes in population structure. Because candi-
demia surveillance took place in both Atlanta and Baltimore
over two different time periods, 15 years apart for Atlanta and
10 years apart for Baltimore, temporal changes in the C. gla-
brata populations could be observed. The single statistically
significant change that was observed between current and past
populations was an increase in ST16 in Atlanta during the 2008
surveillance compared to the earlier (1992) surveillance period
(P ? 0.013; Fisher’s exact test). ST16 represented approxi-
mately 40% of the 2008 Atlanta survey compared to only 4%
from 1992 to 1993. An increase was also observed for ST3,
although it was not statistically significant.
The temporal changes in genetic diversity in the populations
between the previous and current surveillance studies are pri-
marily due to the gain and loss of STs represented by single
FIG. 1. Neighbor-joining trees for each population in this study showing the abundance of each genotype in the population. (A) Atlanta, 1992;
(B) Atlanta, 2008; (C) Baltimore, 1998; (D) Baltimore, 2008; (E) San Francisco, 1992. Circles represent the percentage of each population of a
given ST. Major STs ST3, ST16, and ST19 are shaded in gray or black.
VOL. 9, 2010 MLST OF C. GLABRATA ISOLATES FROM THE UNITED STATES621
isolates. In Baltimore from 1998 to 2000, there were 17 STs
comprised of 55 different combined alleles. In 2008, nine of
these STs were lost, and an additional five were gained. How-
ever, there was a net loss of 11 alleles in the population. In
Atlanta from 1992 to 1993, there were 11 STs comprised of 45
alleles. In 2008, the number of isolates in the population had
more than doubled, but the number of STs climbed to only 14,
with a loss of five STs, a gain of eight STs, and a net loss of four
Geographic changes in population structure. Only two STs
represented by more than one isolate were unique to a partic-
ular region. Six isolates from Baltimore were ST18, and two
isolates from Atlanta were ST24. There were no STs which
were unique to San Francisco. A total of 12 and 8 STs were
found to be unique to the Baltimore and Atlanta populations,
respectively. Further analysis revealed that for all six loci, there
were 30 and 13 alleles that were unique to the Baltimore and
Atlanta populations, respectively, and that these alleles were
evenly divided across the loci. Locus NMT1 had the highest
number, with 11 unshared alleles. In addition, we observed that
there were ?20 individual polymorphisms that were unshared
between groups and that these were divided approximately
evenly between the two populations.
Measures of genetic distance between populations. In order
to assess genetic diversity among the populations, Wright’s
fixation index (FST) and Nei’s genetic distance (DN) values
were calculated for each locus for all pairwise combinations of
the five populations (Table 2). FSTmeasures the diversity be-
tween populations at an individual locus. The two population
pairs that differ geographically but not temporally, San Fran-
cisco and Atlanta from 1992 to 1993 and Atlanta and Balti-
more 2008, showed little difference in their population struc-
ture, as indicated by their low FSTvalues, and had average FST
values that were lower than the overall mean (Table 2). The
two temporally isolated Baltimore populations had the lowest
FSTvalues of all the pairwise comparisons, an indication that
there was little genetic diversity between the two populations
when measured at the level of individual loci. For the two
temporally separated Atlanta populations, the FSTvalues were
higher than the overall average, which may be a reflection of
the shift in major STs within these populations. The pairwise
populations with the highest mean FSTvalues in all of the
comparisons were San Francisco in 1992 compared to Atlanta
in 2008, which reflected the large temporal and geographic
distance between these two populations. Overall, however,
very few of the FSTvalues were found to be significantly above
0.05, normally considered to be the cutoff between little and
moderate differentiation (9), indicating that the allelic identity
between populations was higher than the identity within pop-
Nei’s genetic identity values were calculated pairwise among
all populations. Again, the values suggested that when all loci
are considered simultaneously, the five populations are rela-
tively undifferentiated. As similarly seen using FSTvalues, the
1992-to-1993 Atlanta population was the most divergent from
the other populations, the largest value was for the populations
with the greatest geographic and temporal isolation (San Fran-
cisco 1992 and Atlanta 2008), and the two Baltimore popula-
tions were the most similar (Table 2).
Analysis of recombination. To determine the extent of
clonality and recombination in the different populations, we
used three different tests of linkage disequilibrium (LD): two
measures of association (IAand rBarD) and a two-locus LD
test by the use of all pairwise allelic combinations. Since clonal
reproduction can mask the effects of recombination, we pre-
pared two data sets. One included all strains of each ST, and
the other included the clone-corrected data of each ST from
which identical genotypes were removed (haplotypes only).
For the two-locus LD test, all five populations and the total
combined population gave similar results. Considering that
each locus had between four and eight alleles, there were
approximately 1,300 total pairwise comparisons. As seen in
Table 3, a large majority of combinations showed significant
LD (P ? 0.05), thus contradicting the null hypothesis of re-
In the association tests, the Index of Association (IA) and
rBarD are expected to be zero if populations are freely recom-
bining and greater than zero if there is association between
alleles (clonality). The rBarD statistic takes into consideration
the number of loci tested and is considered a more robust
measure of association (1). For the uncorrected populations,
both IAand rBarD tests rejected the null hypothesis of recom-
TABLE 2. FSTand Nei’s distance values for subdivided populationsa
FKS LEU2NMT TRPUGP URA3
Atlanta (1992) vs San Francisco (1992)
Atlanta (1992) vs Baltimore (1998)
Atlanta (1992) vs Atlanta (2008)
Atlanta (1992) vs Baltimore (2008)
San Francisco (1992) vs Baltimore (1998)
San Francisco (1992) vs Atlanta (2008)
San Francisco (1992) vs Baltimore (2008)
Baltimore (1998) vs Atlanta (2008)
Baltimore (1998) vs Baltimore (2008)
Atlanta (2008) vs Baltimore (2008)
All populations 230 0.03270.04570.03250.03600.0447 0.0466 0.0397
aFST? (Ht ? Hs)/Ht.
bn ? population size.
cDN, Nei’s unbiased measure of genetic distance.
622LOTT ET AL.EUKARYOT. CELL
bination in all five cases as well as the total isolates considered
to be a single population. For the clone-corrected populations,
all but the 1992 Atlanta population could be rejected at a P
value of ?0.01. The 1992 Atlanta population had a probability
for both IAand rBarD of 0.05.
Combined analysis of the populations. A neighbor-joining
tree was constructed to show the genetic relationship among
the 31 observed STs in our combined populations (Fig. 2). All
seven of the groups defined by Dodgson and coworkers (4, 5)
from two global population studies of C. glabrata isolates were
identified in our collection, and the isolates themselves showed
a high degree of diversity. Bootstrap values were high among
paired isolates but dropped off considerably when larger
groups were compared (data not shown). Our analysis supports
previous findings (4) that group III partitions into subgroups A
and B and that group II is better resolved than are groups I
and IV (4).
The present study was undertaken as part of a long-term
prospective surveillance to determine species distribution and
drug resistance profiles in hospital-associated Candida blood-
stream infections (8, 10). Isolates studied were all incident
bloodstream isolates collected from residents of each surveil-
lance area. From a total of 230 isolates, representing the se-
quencing of ?7.7 ? 105base pairs, we observed only two
new mutations, both nonsynonymous polymorphisms. We de-
scribed six additional isolates as new STs resulting from new
combinations of existing alleles.
A number of interesting observations have resulted from this
analysis. For these selected U.S. isolates, the uncovering of
new polymorphisms (by definition, new alleles) may be increas-
ingly proportional to the number of isolates examined, suggest-
ing a finite number of alleles in the population. The definition
of an allele as a discrete set of polymorphisms as described by
Dodgson et al. (4) is strongly supported, with little evidence of
homoplasy in the creation of allelic combinations. There is
evidence from our analysis for recombination in this species.
Because alleles and STs are shared among all populations in
this study, this implies that recombination has, or is, occurring
among our defined populations. Earlier studies have suggested
that such recombination is sexual (meiotic) recombination (3,
5). As in earlier work (4), our data supports the concept that
these six unlinked loci are representative of the genome as a
whole and reflect the underlying mechanisms creating diversity
and differentiation in this species.
We have also provided evidence that there is a clonal com-
ponent to the population, such as the increasing proportion of
ST16 in Atlanta and the overall abundance both temporally
and geographically of ST16, ST19, and ST3. The temporal
stability of some STs suggests that at least some isolates with
identical STs may be related by descent. More specifically, the
isolates in the major STs may be clonally related. Both the IA
and linkage association analyses support this concept, even
when populations were clone corrected. Our findings are in
agreement with other published work (4) and are supported by
the knowledge that these MLST loci are physically unlinked
(18). Additionally, we have reanalyzed IAand rBarD for a
subpopulation of 20 isolates containing groups I, IV, V, VI,
and VII. As seen in Fig. 2, this large middle group of STs are
lacking in bootstrap support for the branch nodes. The IAand
rBarD values for the clone-corrected subpopulation were
found to be 0.598 and 0.135, respectively. Although still below
the level of statistical significance for recombination (P ?
FIG. 2. Neighbor-joining dendrogram for the 31 STs identified in
this study. Major groups previously identified (4) are indicated. Hori-
zontal bar indicates percent divergence. Bootstrap values above 60%
are indicated at nodes (replicates ? 1,000).
TABLE 3. Multilocus LD analyses in each of the
Value for all
114 0.311 0.075
All isolates 23031 3.01b
aNormalized LD. The number of significant (P ? 0.05) linkage disequilibria
from all possible pairwise combinations of all alleles.
bP ? 0.01.
VOL. 9, 2010 MLST OF C. GLABRATA ISOLATES FROM THE UNITED STATES623
0.02), these values are less than those for the the combined
population as a whole (Table 3). We interpret this as suggest-
ing that some subpopulations may be recombining at low, but
From a population standpoint, we have observed slight dif-
ferences in the overall abundance of individual STs among
geographic groups, primarily among minor STs, although fre-
quency shifts in the major STs were also found. This is consis-
tent with other observations which have shown FSTvalues
between cities and countries to be generally smaller than those
between continents (3). Our data showing that the C. glabrata
population in three large U.S. cities consists of a relatively
small number of major STs are consistent with the previous
study of U.S. isolates, in which the same and other major STs
were observed (4). For example, STs 3 and 10 have been shown
to be major STs worldwide (4). Some of the major STs in other
collections do not appear in ours, while one of the major STs
observed in this study, ST16, appears to be restricted to the
United States (4, 11, 12). In addition, we observed a large
temporal increase in the frequency of ST16 in Atlanta. Taken
collectively, this suggests that STs may vary, or drift, between
major and minor types over distance and time. The abundance
of a particular ST in a geographic locale may be a reflection of
the adaptation of a specific ST to a geographic niche, while the
general drift in the temporal and geographic populations may
reflect the ability of isolates of C. glabrata to adapt to new
The low FSTand genetic distance values among the popu-
lations are, in part, a reflection of the relative abundance in
each population of the three major STs, ST19, ST16, and ST3,
which account for an average of 50% of the isolates across all
populations. The amount of diversity within a population
ranged from one unique ST for every 2.4 isolates in Atlanta
from 1992 to 1993 to one unique ST for every 4.8 patients in
Baltimore in 2008. Two other studies of ST diversity of C.
glabrata isolates have been recently published. Odds and co-
workers (12) identified 27 STs from 50 patients in a 1-year
study of Candida isolates from Scotland, for a ratio of one
unique ST for every 1.9 isolates. Lin and coworkers (11) iden-
tified 15 STs from 37 patients in a single hospital in Taiwan
over 2 years, for a ratio of one unique ST for every 2.5 isolates.
Ratios from both of these previous studies indicate a higher
degree of diversity in these populations in terms of STs than we
have found. However, ST is not indicative of overall allelic
diversity within a population. Because neither dendrograms
nor individual STs were provided in either of the previous
studies, it is not possible to tell whether the ST diversity is a
reflection of overall diversity or whether it reflects a diverse
population of closely related isolates. The populations ob-
served in the other studies were also not bound by the con-
straints of case patient residency in a defined geographic
There is an intriguing correlation between genetic distance
measures and incidence rates in the Atlanta and Baltimore
populations. When the two Baltimore populations were com-
pared temporally, they were shown to be highly similar genet-
ically. The incidence rate of C. glabrata in Baltimore from 1998
to 2000 was 6.6/100,000 (8). Preliminary analysis showed that
this rate dropped only slightly in 2008 to 6.3/100,000 (2). In
contrast, the largest amount of genetic diversity was seen be-
tween the two Atlanta populations when they were compared
temporally. The incidence rate of C. glabrata in Atlanta from
1992 to 1993 was only 0.96/100,000 (10). Preliminary analysis
showed that in 2008 the incidence rate in Atlanta was 3.9/
100,000 (2). It is interesting to note that the large change in the
C. glabrata population structure in Atlanta also correlated with
an increased incidence rate. While there are multiple factors
that contribute to an increased incidence rate, it is reasonable
to speculate that changes in the population structure of the
organism, perhaps to better fill an available niche, played a
contributing role. Knowledge of the population genetic struc-
ture of the various C. glabrata populations within the ongoing
candidemia surveillance will contribute significantly to our fur-
ther analysis of incidence rates, patient outcomes, and antifun-
gal resistance within these populations. Research to better
understand these relationships is ongoing.
We acknowledge the significant contributions of the following mem-
bers of the CDC Candidemia Surveillance Group: Angela Ahlquist,
Monica Farley, Lee Harrison, Wendy Baughman, Betsy Siegel, Rose-
mary Hollick, Kizee Etienne, Eszter Deak, Joyce Peterson, Naureen
Iqbal, Lauren Smith, and Tom Chiller. We thank the staff of all the
institutions that contributed isolates to this study. We thank Arun
Balajee for critical reading of the manuscript. We also acknowledge
the members of the DFBMD core sequencing laboratory at the Cen-
ters for Disease Control and Prevention for their technical assistance.
The findings and conclusions of this article are those of the authors
and do not necessarily represent the views of the Centers for Disease
Control and Prevention.
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