Affiliation:
1. W. M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA
2. Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China
3. Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA
Abstract
ABSTRACT
The first genome sequence of a group A
Streptococcus pyogenes
serotype M23 (
emm23
) strain (M23ND), isolated from an invasive human infection, has been completed. The genome of this opacity factor-negative (SOF
−
) strain is composed of a circular chromosome of 1,846,477 bp. Gene profiling showed that this strain contained six phage-encoded and 24 chromosomally inherited well-known virulence factors, as well as 11 pseudogenes. The bacterium has acquired four large prophage elements, ΦM23ND.1 to ΦM23ND.4, harboring genes encoding streptococcal superantigen (
ssa
), streptococcal pyrogenic exotoxins (
speC
,
speH
, and
speI
), and DNases (
spd1
and
spd3
), with phage integrase genes being present at one flank of each phage insertion, suggesting that the phages were integrated by horizontal gene transfer. Comparative analyses revealed unique large-scale genomic rearrangements that result in genomic rearrangements that differ from those of previously sequenced GAS strains. These rearrangements resulted in an imbalanced genomic architecture and translocations of chromosomal virulence genes. The
covS
sensor in M23ND was identified as a pseudogene, resulting in the attenuation of
speB
function and increased expression of the genes for the chromosomal virulence factors multiple-gene activator (
mga
), M protein (
emm23
), C5a peptidase (
scpA
), fibronectin-binding proteins (
sfbI
and
fbp54
), streptolysin O (
slo
), hyaluronic acid capsule (
hasA
), streptokinase (
ska
), and DNases (
spd
and
spd3
), which were verified by PCR. These genes are responsible for facilitating host epithelial cell binding and and/or immune evasion, thus further contributing to the virulence of M23ND. In conclusion, strain M23ND has become highly pathogenic as the result of a combination of multiple genetic factors, particularly gene composition and mutations, prophage integrations, unique genomic rearrangements, and regulated expression of critical virulence factors.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
20 articles.
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