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Infection and Immunity, October 1998, p. 4593-4601, Vol. 66, No. 10
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Streptococcus pyogenes Serotype M1
Encodes Multiple Pathways for Entry into Human Epithelial
Cells
D.
Cue,
P. E.
Dombek,
H.
Lam, and
P. P.
Cleary*
Department of Microbiology, University of
Minnesota, Minneapolis, Minnesota
Received 23 March 1998/Returned for modification 18 May
1998/Accepted 2 July 1998
The ability of a serotype M1 strain of Streptococcus
pyogenes to efficiently invade A549 human lung epithelial cells
was previously shown to be dependent on bacterial exposure to human or
bovine serum proteins or synthetic peptides containing the sequence
RGD. In this study, stimulation by invasion agonists was determined to
be dependent on expression of the streptococcal cell surface protein,
M1. Fetal bovine serum (FBS), fibronectin (Fn), the extracellular matrix protein laminin (Lm), and RGD-containing peptides were tested
for their abilities to promote epithelial cell invasion and adherence
by isogenic M1+ and M1
strains of S. pyogenes. In the absence of an agonist, invasion and adherence
were comparable for the two bacterial strains. FBS, Fn, and Lm
stimulated invasion of the M1+ strain as much as 70-fold
but failed to significantly affect invasion by the M1
mutant. Adherence of the wild-type strain was stimulated by these same
agonists. Epithelial cell adherence by the M1
strain,
however, was unaffected by the presence of Fn or Lm. Several
RGD-containing peptides were found to promote invasion independently of
M1 expression. Binding of 125I-Fn was reduced 88% by the
M1
mutation and Fn was found to bind purified M1 protein,
suggesting that Fn mediates invasion by direct binding to M1. To
determine if host integrins might be involved in internalization of
streptococci, several anti-integrin monoclonal antibodies (MAbs) were
tested for their abilities to inhibit invasion. Antibody directed
against integrin
1 inhibited FBS-, Fn-, and Lm-mediated invasion but did not abrogate RGD-peptide-stimulated invasion. MAb directed against
the epithelial cell Fn receptor, integrin
5
1, inhibited Fn and
FBS-mediated invasion but did not specifically inhibit Lm-mediated
invasion. These results indicate that S. pyogenes has
evolved multiple mechanisms for invasion of eukaryotic cells, at least
two of which involve interactions between M1 protein, host integrins,
and integrin ligands.
*
Corresponding author. Mailing address: Box 196 UMHC,
Department of Microbiology, University of Minnesota, Minneapolis, MN 55455. Phone: (612) 624-3932. Fax: (612) 626-0623. E-mail:
Cleary{at}lenti.med.umn.edu.
Infection and Immunity, October 1998, p. 4593-4601, Vol. 66, No. 10
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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