Genome Sequence of a Nephritogenic and Highly Transformable M49 Strain ofStreptococcus pyogenes

Abstract

The 1,815,783-bp genome of a serotype M49 strain of Streptococcus pyogenes (group A streptococcus [GAS]), strain NZ131, has been determined. This GAS strain (FCT type 3; emm pattern E), originally isolated from a case of acute post-streptococcal glomerulonephritis, is unusually competent for electrotransformation and has been used extensively as a model organism for both basic genetic and pathogenesis investigations. As with the previously sequenced S. pyogenes genomes, three unique prophages are a major source of genetic diversity. Two clustered regularly interspaced short palindromic repeat (CRISPR) regions were present in the genome, providing genetic information on previous prophage encounters. A unique cluster of genes was found in the pathogenicity island-like emm region that included a novel Nudix hydrolase, and, further, this cluster appears to be specific for serotype M49 and M82 strains. Nudix hydrolases eliminate potentially hazardous materials or prevent the unbalanced accumulation of normal metabolites; in bacteria, these enzymes may play a role in host cell invasion. Since M49 S. pyogenes strains have been known to be associated with skin infections, the Nudix hydrolase and its associated genes may have a role in facilitating survival in an environment that is more variable and unpredictable than the uniform warmth and moisture of the throat. The genome of NZ131 continues to shed light upon the evolutionary history of this human pathogen. Apparent horizontal transfer of genetic material has led to the existence of highly variable virulence-associated regions that are marked by multiple rearrangements and genetic diversification while other regions, even those associated with virulence, vary little between genomes. The genome regions that encode surface gene products that will interact with host targets or aid in immune avoidance are the ones that display the most sequence diversity. Thus, while natural selection favors stability in much of the genome, it favors diversity in these regions. Group A streptococcus ([GAS] Streptococcus pyogenes)causes a wide range of human diseases ranging from uncomplicated pharyngitis to life-threatening invasive disease. Acute post-streptococcal glomerulonephritis (APSGN) is one of the nonsuppurative sequelae that can occur following a GAS infection; the other common postinfection sequelae are rheumatic heart disease. Worldwide, it is estimated that approximately 470,000 cases of APSGN occur annually (23). Children and young adults are affected most commonly, with males having twice the incidence as females (74). By the 1940s, evidence was found that streptococcal skin infections were associated with APSGN, and these infections usually did not cause rheumatic fever, leading to the hypothesis that certain GAS strains were "rheumatogenic" while others were "nephritogenic" (41, 72). Further, divergent seasonal patterns of peak incidence exist separating nephritogenic and rheumatogenic GAS, with APSGN cases peaking in the late summer simultaneously with skin infections w...

Insights from Genomics on Post-Infectious Streptococcal Glomerulonephritis

“…Strain NZ131 has 1,699 predicted open reading frames (ORFs) that use 1,548,919 bases so that 85.3% of the genomic DNA is used as coding sequences. The base composition of the ORFs is 39.18% G+C while the composition of the total genome is 38.57%; both values are similar to the composition seen in the other completed GAS genomes (McShan et al, 2008). The MGCS10565 genome has a 42.59% G+C content, and its genome has 1,961 predicted ORFs, which require 85% of the genome (Beres et al, 2008).…”

“…zooepidemicus MGCS10565 (group C) were completely sequenced in independent efforts in 2008 (Beres et al, 2008;McShan et al, 2008). Both of these isolates were originally isolated from cases of human glomerulonephritis (Beres et al, 2008;McShan et al, 2008); additionally, NZ131 has been also studied intensively in over thirty published studies (McShan et al, 2008).…”

Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences

“…ICEs (25). Common GAS prophage-encoded virulence factors include pyrogenic toxin superantigens, extracellular DNases, and a secreted phospholipase A2 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). GAS ICE-encoded antimicrobial agents typically include those mediating resistance to tetracycline or macrolides (34).…”

Analysis of CRISPR in Streptococcus mutans suggests frequent occurrence of acquired immunity against infection by M102-like bacteriophages

“…1b). The first repeat is identical to a CRISPR repeat present in the genome of Streptococcus pyogenes M49 (McShan et al, 2008). It is a member of repeat cluster 3 (Kunin et al, 2007), associated with subtype Dvulg cas genes (Haft et al, 2005).…”