Evolution of Transcription Regulatory Genes Is Linked to Niche Specialization in the Bacterial Pathogen Streptococcus pyogenes

Abstract

Streptococcus pyogenes is a highly prevalent bacterial pathogen, most often giving rise to superficial infections at the throat or skin of its human host. Three genotype-defined subpopulations of strains exhibiting strong tropisms for either the throat or skin (specialists) or having no obvious tissue site preference (generalists) are recognized. Since the microenvironments at the throat and skin are distinct, the signal transduction pathways leading to the control of gene expression may also differ for throat versus skin strains of S. pyogenes. Two loci (mga and rofA/nra) encoding global regulators of virulence gene expression are positioned 300 kb apart on the genome; each contains alleles forming two major sequence clusters of ϳ25 to 30% divergence that are under balancing selection. Strong linkage disequilibrium is observed between sequence clusters of the transcription regulatory loci and the subpopulations of throat and skin specialists, against a background of high recombination rates among housekeeping genes. A taxonomically distinct commensal species (Streptococcus dysgalactiae subspecies equisimilus) shares highly homologous rof alleles. The findings provide strong support for a mechanism underlying niche specialization that involves orthologous replacement of regulatory genes following interspecies horizontal transfer, although the directionality of gene exchange remains unknown.

Deriving Group A Streptococcus Typing Information from Short-Read Whole-Genome Sequencing Data

“…We identified a few discrepancies between our results and previously found patterns of genes in GAS strains (16). Namely, some of the GAS emm types (emm73 and emm105) described in previous reports (16) as containing gene nra were found in this study to instead contain gene rofA, while type emm29 strains were found here to contain gene nra and not gene rofA as had been reported previously (16). Finally we used SRST2 to reveal whether the GAS strains possessed the mga1 or mga2 alleles of the mga gene directly from the short-read WGS data (see Table S1 in the supplemental material).…”

“…Overall and despite the presence of these ambiguities, our data showed strong correlations between emm types and MLST STs for the vast majority of the isolates (see Table S1 in the supplemental material), which probably is a reflection of the clonal nature of the GAS strains circulating in Ontario. We also used SRST2 to determine the presence or absence in our strains of markers associated with host-tissue tropism in GAS (14,16,17), including genes sof, nra, and rofA (see Table S1 in the supplemental material). We identified a few discrepancies between our results and previously found patterns of genes in GAS strains (16).…”

“…We also used SRST2 to determine the presence or absence in our strains of markers associated with host-tissue tropism in GAS (14,16,17), including genes sof, nra, and rofA (see Table S1 in the supplemental material). We identified a few discrepancies between our results and previously found patterns of genes in GAS strains (16). Namely, some of the GAS emm types (emm73 and emm105) described in previous reports (16) as containing gene nra were found in this study to instead contain gene rofA, while type emm29 strains were found here to contain gene nra and not gene rofA as had been reported previously (16).…”

“…It has been suspected that at least one of the sequences present in the CDC emm database may correspond to mrp or enn in a minority of strains (15). Together with the presence and/or absence of other markers such as nra and rofA, which encode regulators of pili expression, pili genes themselves, and sof, encoding a serum opacity factor, emm chromosomal arrangements have been used as putative predictors of host-tissue tropism for GAS strains (14,16,17). Multilocus sequence typing (MLST) schemes have also been developed and used to type GAS isolates (18,19).…”

Domains Required for Transcriptional Activation Show Conservation in the Mga Family of Virulence Gene Regulators

“…Furthermore, two mga alleles have been described within the GAS (mga-1 and mga-2) based upon the ability to hybridize to an oligonucleotide probe (12) and are associated with different gene patterns at the mga locus and tissue tropism of the serotype (11). The Mga proteins produced from the two alleles are most divergent within the C-terminal end of the protein (2), showing a maximal amino acid divergence of 20.7% (3). Despite the divergence, both mga alleles have been shown to be functionally equivalent in an mga-1 deletion strain (2).…”