title: Differences in virulence repertoire and cell invasive potential of group A Streptococcus emm1-2 in comparison to emm1 genotype.
abstract: Group A streptococcus (GAS, Streptococcus pyogenes) type emm1 is widely associated with streptococcal invasive disease. This type is prevalent worldwide but is rare in India. Instead, emm1-2 type which is closely related to emm1 but is a distinct type is more prevalent. Although emm1 has been well characterized, information available on emm1-2 is rare. In this study we present a comparative study of both types. DNA microarray analysis showed segregation of emm1 and emm1-2 isolates into two distinct clusters. Out of 229 arrayed genes, 83-87% were present, 6-9% absent and 4-8% genes were ambiguous in emm1 isolates. emm1-2 strains harboured only 68-77%, 11-13% were absent and 10-20% ambiguous genes. Fourteen genes, present in all emm1, were completely absent in the emm1-2 isolates. sfb1 is a gene which encodes for Streptococcal fibronectin binding adhesin and invasin which has restricted distribution among different emm types of GAS. A variant of sfb1 (sfb1-2) was the only gene which was present in all emm1-2 isolates, but absent from all emm1 strains. Sfb1 and Sfb1-2 differ in sequences in the aromatic domain and the proline rich repeat region, whereas the fibronectin binding region was conserved and exhibited similar fibronectin binding activity. The presence of Sfb1-2 in emm1-2 strains was concomitant with significantly higher fibronectin-binding and invasion efficiency of HEp-2 cells when compared to emm1 isolates. The role of Sfb1-2 in invasion was confirmed by latex bead assay. emm1-2 isolates follow membrane ruffling mechanism during invasion and intracellularly follow classical endocytic pathway. Further studies are required to understand the correlation between the presence of emm1-2 isolates and the disease pattern in North India.
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany; Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address: vivekgenetics@gmail.com.
authors.forename: Vivek
authors.initials: V
authors.lastname: Sagar
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Rene
authors.initials: R
authors.lastname: Bergmann
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Nerlich
authors.affiliation: Bacterial Pathogenesis Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia and Inflammation and Healing Research Cluster, School of Health and Sport Sciences, University of the Sunshine Coast, Sippy Downs, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: McMillan
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: D Patric
authors.initials: DP
authors.lastname: Nitsche-Schmitz
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Fulde
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Talay
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.affiliation: National Institute of Health, Hamilton, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Hoe
authors.affiliation: Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Chakraborti
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Gursharan S
authors.initials: GS
authors.lastname: Chhatwal
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016000:Cluster Analysis; D005838:Genotype; D006801:Humans; D007194:India; D046228:Microarray Analysis; D020411:Oligonucleotide Array Sequence Analysis; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000254:growth & development*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; C099983:Emm2 protein, Streptococcus pyogenes; D037521:Virulence Factors; C014689:streptococcal M protein
keywords: Group A streptococcus; Invasion; Sfb1-2; Streptococcus pyogenes; emm1; emm1-2