title: Acquisition of the Sda1-encoding bacteriophage does not enhance virulence of the serotype M1 Streptococcus pyogenes strain SF370.
abstract: The resurgence of invasive disease caused by Streptococcus pyogenes (group A Streptococcus [GAS]) in the past 30 years has paralleled the emergence and global dissemination of the highly virulent M1T1 clone. The GAS M1T1 clone has diverged from the ancestral M1 serotype by horizontal acquisition of two unique bacteriophages, encoding the potent DNase Sda1/SdaD2 and the superantigen SpeA, respectively. The phage-encoded DNase promotes escape from neutrophil extracellular traps and is linked to enhanced virulence of the M1T1 clone. In this study, we successfully used in vitro lysogenic conversion to transfer the Sda1-encoding phage from the M1T1 clonal strain 5448 to the nonclonal M1 isolate SF370 and determined the impact of this horizontal gene transfer event on virulence. Although Sda1 was expressed in SF370 lysogens, no capacity of the phage-converted strain to survive human neutrophil killing, switch to a hyperinvasive covRS mutant form, or cause invasive lethal infection in a humanized plasminogen mouse model was observed. This work suggests that the hypervirulence of the M1T1 clone is due to the unique synergic effect of the M1T1 clone bacteriophage-specific virulence factor Sda1 acting in concert with the M1T1 clone-specific genetic scaffold.
authors.affiliation: School of Chemistry and Molecular Bioscience and Australian Infectious Diseases Research Centre, The University of Queensland, St. Lucia, QLD, Australia.
authors.forename: Carola
authors.initials: C
authors.lastname: Venturini
authors.forename: Cheryl-Lynn Y
authors.initials: CL
authors.lastname: Ong
authors.forename: Christine M
authors.initials: CM
authors.lastname: Gillen
authors.forename: Nouri L
authors.initials: NL
authors.lastname: Ben-Zakour
authors.forename: Peter G
authors.initials: PG
authors.lastname: Maamary
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: Scott A
authors.initials: SA
authors.lastname: Beatson
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Walker
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D003850:Deoxyribonuclease I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D017108:Streptococcus Phages / Q000235:genetics / Q000378:metabolism*; D013297:Streptococcus pyogenes / Q000472:pathogenicity* / Q000821:virology*; D014774:Virulence
chemical_list: D004269:DNA, Bacterial; D003850:Deoxyribonuclease I; C493845:Sda1 protein, Streptococcus pyogenes