title: Evolution of diversity in epidemics revealed by analysis of the human bacterial pathogen group A Streptococcus.
abstract: Advancements in high-throughput, high-volume data generating techniques increasingly present us with opportunities to probe new areas of biology. In this work we assessed the extent to which four closely related and genetically representative strains of group A Streptococcus causing epidemic disease have differentiated from one another. Comparative genome sequencing, expression microarray analysis, and proteomic studies were used in parallel to assess strain variation. The extent of phenotypic differentiation was unexpectedly large. We found significant associations between genetic polymorphisms and alterations in gene expression allowing us to estimate the frequency with which specific types of polymorphisms alter gene transcription. We identified polymorphisms in the gene (ropB) encoding the RopB regulator that associate with altered transcription of speB and production of the SpeB protein, a critical secreted protease virulence factor. Although these four epidemic strains are closely related, a key discovery is that accumulation of modest genetic changes has rapidly resulted in significant strain phenotypic differentiation, including the extracellular proteome that contains multiple virulence factors. These data provide enhanced understanding of genetic events resulting in strain variation in bacterial epidemics.
authors.affiliation: Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital System, Houston, TX 77030, USA.
authors.forename: Ronan K
authors.initials: RK
authors.lastname: Carroll
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Beres
authors.forename: Izabela
authors.initials: I
authors.lastname: Sitkiewicz
authors.forename: Leif
authors.initials: L
authors.lastname: Peterson
authors.forename: Risë K
authors.initials: RK
authors.lastname: Matsunami
authors.forename: David A
authors.initials: DA
authors.lastname: Engler
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Flores
authors.forename: Paul
authors.initials: P
authors.lastname: Sumby
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D044822:Biodiversity; D005075:Biological Evolution; D005098:Exotoxins / Q000235:genetics*; D005786:Gene Expression Regulation; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D046228:Microarray Analysis; D010641:Phenotype; D011110:Polymorphism, Genetic; D040901:Proteomics; D013290:Streptococcal Infections / Q000453:epidemiology* / Q000235:genetics* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D005098:Exotoxins; C098249:RopB protein, Rhizobium leguminosarum; D037521:Virulence Factors; C027951:erythrogenic toxin