Evolutionary Origin and Emergence of a Highly Successful Clone of Serotype M1 Group AStreptococcusInvolved Multiple Horizontal Gene Transfer Events

Abstract

To better understand the molecular events involved in the origin of new pathogenic bacteria, we studied the evolution of a highly virulent clone of serotype M1 group A Streptococcus (GAS). Genomic, DNA-DNA microarray, and single-nucleotide polymorphism analyses indicated that this clone evolved through a series of horizontal gene transfer events that involved (1) the acquisition of prophages encoding streptococcal pyrogenic exotoxin A and extracellular DNases and (2) the reciprocal recombination of a 36-kb chromosomal region encoding the extracellular toxins NAD+-glycohydrolase (NADase) and streptolysin O (SLO). These gene transfer events were associated with significantly increased production of SLO and NADase. Virtual identity in the 36-kb region present in contemporary serotype M1 and M12 isolates suggests that a serotype M12 strain served as the donor of this region. Multiple horizontal gene transfer events were a crucial factor in the evolutionary origin and emergence of a very abundant contemporary clone of serotype M1 GAS.

A novel coiled-coil repeat variant in a class of bacterial cytoskeletal proteins

“…It is very rich in alanine (23%) and charged residues: 19% glutamate and 14% arginine (but only 4% aspartate and 3% lysine). This composition is somewhat similar to the much shorter, heptad-based, surface-expressed streptococcal M-proteins (Sumby et al, 2005;Fischetti, 1989), although the latter contain more leucine (12% compared to Scy's 7%).…”

Toward a Genome-Wide Systems Biology Analysis of Host-Pathogen Interactions in Group A Streptococcus

“…Virtually all GAS prophages encode one or two proven or putative extracellular virulence factors such as pyrogenic toxin superantigens (PTSAgs), DNAses, novel phospholipase A 2 (SlaA), efflux pump responsible for resistance to macrolide antibiotics, and a novel cell wall-anchored protein hypothesized to be an adhesin. [23][24][25][26][27][28][29] Many of these prophage-associated virulence factor genes were unknown before their discovery by GAS genome sequencing projects. Additional specific discoveries revealed by the genome sequencing projects are described below.…”

“…28,46 This study was greatly facilitated by the availability of the genome sequence of one serotype M1 GAS organism (strain SF370). 22 Inasmuch as strain SF370 is genetically distinct from the great majority of strains responsible for contemporary infections caused by M1 strains, and is less virulent, we hypothesized that acquisition of novel genetic elements had created an unusually successful clone of serotype M1.…”

“…Several expression microarray studies have examined GAS, and extensive new information has been obtained about the nature and extent of changes in the pathogen's transcriptome in response to various perturbations. 28,[51][52][53][54][55][56] This global approach to understanding pathogenesis was facilitated by the information obtained from GAS genome sequencing projects, as described above. Initial studies used conventional spotted microarrays and focused on in vitro analysis, but more recently a custom Affymetrix high-density oligonucleotide array has been used for ex vivo and in vivo studies.…”

“…[22][23][24][25][26][27][28] The availability of genome sequences of M protein serotypes causing distinct diseases has yielded a tremendous amount of new information important for a systems biology approach to pathogenesis research.…”