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, 40 (5), 1805-10

Molecular Analysis of Group A Streptococcus Type emm18 Isolates Temporally Associated With Acute Rheumatic Fever Outbreaks in Salt Lake City, Utah

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Molecular Analysis of Group A Streptococcus Type emm18 Isolates Temporally Associated With Acute Rheumatic Fever Outbreaks in Salt Lake City, Utah

James C Smoot et al. J Clin Microbiol.

Abstract

Acute rheumatic fever (ARF) and subsequent rheumatic heart disease are rare but serious sequelae of group A Streptococcus (GAS) infections in most western countries. Salt Lake City (SLC), Utah, and the surrounding intermountain region experienced a resurgence of ARF in 1985 which has persisted. The largest numbers of cases were encountered in 1985-1986 and in 1997-1998. Organisms with a mucoid colony phenotype when grown on blood agar plates were temporally associated with the higher incidence of ARF. To develop an understanding of the molecular population genetic structure of GAS strains associated with ARF in the SLC region, 964 mucoid and nonmucoid pharyngeal isolates recovered in SLC from 1984 to 1999 were studied by sequencing the emm gene. Isolates with an emm18 allele were further characterized by sequencing the spa, covR, and covS genes. Peak periods of ARF were associated with GAS isolates possessing an emm18 allele encoding the protein found in serotype M18 isolates. Among the serotype M18 isolates, the difference in the number of C repeats produced three size variants. Variation was limited in spa, a gene that encodes a streptococcal protective antigen, and covR and covS, genes that encode a two-component regulatory system that, when inactivated, results in a mucoid phenotype and enhanced virulence in mouse infection models. Pulsed-field gel electrophoresis showed a single restriction profile for serotype M18 organisms isolated during both peak periods of ARF. In SLC, the incidence of ARF coresurged with the occurrence of GAS serotype M18 isolates that have very restricted genetic variation.

Figures

FIG. 1.
FIG. 1.
Cases of ARF diagnosed in Salt Lake City Utah from 1960 through 1999.
FIG. 2.
FIG. 2.
Distribution of mucoid and nonmucoid GAS isolates in Salt Lake City from 1984 through 1991 and 1997 through 1999. (A) Mucoid GAS isolates from this collection were dominated by serotype M18 strains during peak incidences of ARF. The frequencies of GAS isolates with the emm18 allele are shown separately (blue bars) for each year. Stacked bars show the frequencies of all other emm types within a given year. The inset is the color code for all remaining emm types presenting a mucoid phenotype identified. Sample sizes are given for each year. (B) Three-dimensional plot showing the distributions of nonmucoid GAS isolates from this collection from 1984 through 1994. The inset is the color code for the years during which isolates were sampled. Samples were normalized across years during which isolates were sampled.
FIG. 3.
FIG. 3.
Distribution of GAS isolates collected at IHC clinics in greater Utah during 1998 and 1999. (A) Mucoid GAS isolates from this collection were dominated by isolates with the emm18 allele. The inset is the frequency distributions for all remaining emm types presenting a mucoid phenotype identified (NT, nontypeable). (B) The distribution of emm types among nonmucoid GAS isolates was more uniform during the same period.
FIG. 4.
FIG. 4.
emm18 size variants within the GAS M18 isolate population in Salt Lake City. (A) Agarose gel showing the three size variants of emm18 PCR fragments with sizes of 825 bp (lane c), 950 bp (lane a), and 1,075 bp (lane b); the unmarked lane on the left contained a 100-bp DNA size marker. (B) Molecular characterization of emm18 size variants discovered that a 126-bp repeat region was responsible for the variation in gene size. The sequence of the repeated region in emm18 that is responsible for the observed size variation is shown (inset), with flanking 19-bp fragments presented in boldface.

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