Plasminogen binding by group A streptococcal isolates from a region of hyperendemicity for streptococcal skin infection and a high incidence of invasive infection.
Reports of resurgence in invasive group A streptococcal (GAS) infections come mainly from affluent populations with infrequent exposure to GAS. In the Northern Territory (NT) of Australia, high incidence of invasive GAS disease is secondary to endemic skin infection, serotype M1 clones are rare in invasive infection, the diversity and level of exposure to GAS strains are high, and no particular strains dominate. Expression of a plasminogen-binding GAS M-like protein (PAM) has been associated with skin infection in isolates elsewhere (D. Bessen, C. M. Sotir, T. M. Readdy, and S. K. Hollingshead, J. Infect. Dis. 173:896-900, 1996), and subversion of the host plasminogen system by GAS is thought to contribute to invasion in animal models. Here, we describe the relationship between plasminogen-binding capacity of GAS isolates, PAM genotype, and invasive capacity in 29 GAS isolates belonging to 25 distinct strains from the NT. In the presence of fibrinogen and streptokinase, invasive isolates bound more plasminogen than isolates from uncomplicated infections (P < or = 0.004). Only PAM-positive isolates bound substantial levels of plasminogen by a fibrinogen-streptokinase-independent pathway (direct binding). Despite considerable amino acid sequence variation within the A1 repeat region of PAM where the plasminogen-binding domain maps, the critical lysine residue was conserved.
McKay
Fiona C
FC
Department of Biological Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia.
McArthur
Jason D
JD
Sanderson-Smith
Martina L
ML
Gardam
Sandra
S
Currie
Bart J
BJ
Sriprakash
Kadaba S
KS
Fagan
Peter K
PK
Towers
Rebecca J
RJ
Batzloff
Michael R
MR
Chhatwal
Gursharan S
GS
Ranson
Marie
M
Walker
Mark J
MJ
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D019353:Endemic Diseases; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D015994:Incidence; D008969:Molecular Sequence Data; D015876:Northern Territory / Q000453:epidemiology; D010958:Plasminogen / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D017192:Skin Diseases, Bacterial / Q000453:epidemiology* / Q000382:microbiology; D013290:Streptococcal Infections / Q000453:epidemiology* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000302:isolation & purification* / Q000378:metabolism
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; C084529:plasminogen-binding protein, bacteria; C014689:streptococcal M protein; D005340:Fibrinogen; D010958:Plasminogen