Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks - PubMed (original) (raw)

Comparative Study

. 2002 Apr 2;99(7):4668-73.

doi: 10.1073/pnas.062526099. Epub 2002 Mar 26.

Kent D Barbian, Jamie J Van Gompel, Laura M Smoot, Michael S Chaussee, Gail L Sylva, Daniel E Sturdevant, Stacy M Ricklefs, Stephen F Porcella, Larye D Parkins, Stephen B Beres, David S Campbell, Todd M Smith, Qing Zhang, Vivek Kapur, Judy A Daly, L George Veasy, James M Musser

Affiliations

Comparative Study

Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks

James C Smoot et al. Proc Natl Acad Sci U S A. 2002.

Abstract

Acute rheumatic fever (ARF), a sequelae of group A Streptococcus (GAS) infection, is the most common cause of preventable childhood heart disease worldwide. The molecular basis of ARF and the subsequent rheumatic heart disease are poorly understood. Serotype M18 GAS strains have been associated for decades with ARF outbreaks in the U.S. As a first step toward gaining new insight into ARF pathogenesis, we sequenced the genome of strain MGAS8232, a serotype M18 organism isolated from a patient with ARF. The genome is a circular chromosome of 1,895,017 bp, and it shares 1.7 Mb of closely related genetic material with strain SF370 (a sequenced serotype M1 strain). Strain MGAS8232 has 178 ORFs absent in SF370. Phages, phage-like elements, and insertion sequences are the major sources of variation between the genomes. The genomes of strain MGAS8232 and SF370 encode many of the same proven or putative virulence factors. Importantly, strain MGAS8232 has genes encoding many additional secreted proteins involved in human-GAS interactions, including streptococcal pyrogenic exotoxin A (scarlet fever toxin) and two uncharacterized pyrogenic exotoxin homologues, all phage-associated. DNA microarray analysis of 36 serotype M18 strains from diverse localities showed that most regions of variation were phages or phage-like elements. Two epidemics of ARF occurring 12 years apart in Salt Lake City, UT, were caused by serotype M18 strains that were genetically identical, or nearly so. Our analysis provides a critical foundation for accelerated research into ARF pathogenesis and a molecular framework to study the plasticity of GAS genomes.

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Figures

Figure 1

Figure 1

Atlas of the chromosome of serotype M18 strain MGAS8232. Arrowheads in the outermost ring depict the position and orientation of all transposase genes or gene fragments identified in the genome. Transposase genes are color coded to represent the transposase family with the closest BLASTP match (red, IS_1239_; black, IS_904A_; olive, IS_1562_; gray blue, tnpA; green, IS 861; light blue, Streptococcus salvarius transposase). The middle three rings show the position and orientation of the six RNA operons (light blue, clockwise; pink, counterclockwise) and ORFs (blue, clockwise; yellow, counterclockwise) identified in the genome. The innermost ring shows the location and name of the phage sequences (orange) identified in the genome.

Figure 2

Figure 2

Dot plot of a

cross_match

comparison of strains MGAS8232 and SF370 genome sequences.

cross_match

was run with default parameters except the minimum match was set to 100. Deflections of segments along either axis indicate insertions of DNA sequence. Segments not aligning on the diagonal line represent sequences that are similar but located in different portions of the genomes. The color of the segments shows the similarity between the nucleotide sequences (green, 72–76%; forest green, 76–80%; light blue, 80–84%; dark blue, 84–88%; maroon, 88–92%; pink, 92–96%; red, 96–100%).

Figure 3

Figure 3

Subset of 223 strain-specific ORFs identified by DNA microarray analysis of 36 serotype M18 strains of GAS. All ORFs had a test/control ratio that either was below the threshold value of 0.7 (yellow) or above the threshold of 1.5 (blue) in at least 1 of 36 strains (black, ORFs with test/control values between the threshold ratios). ORFs are sorted in MGAS8232 genomic order (clockwise from oriC). Strains are numbered 1–36 as they are listed in Table 2. Phage-associated ORFs are identified with a black vertical bar at the phage region. Other ORFs that showed a “gene difference” represent potential transposase genes, transcription regulators, carbohydrate and metal transport genes, and hypothetical genes.

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