Identification and characterization of the scl gene encoding a group a Streptococcus extracellular protein virulence factor with similarity to human collagen
S. Lukomski et al., Identification and characterization of the scl gene encoding a group a Streptococcus extracellular protein virulence factor with similarity to human collagen, INFEC IMMUN, 68(12), 2000, pp. 6542-6553
Group A Streptococcus (GAS) expresses cell surface proteins that mediate im
portant biological functions such as resistance to phagocytosis, adherence
to plasma and extracellular matrix proteins, and degradation of host protei
ns. An open reading frame encoding a protein of 348 amino acid residues was
identified by analysis of the genome sequence available for a serotype M1
strain. The protein has an LPATGE sequence located near the carboxy terminu
s that matches the consensus sequence (LPXTGX) present in many gram-positiv
e cell wall-anchored molecules. Importantly, the central region of this pro
tein contains 50 contiguous Gly-X-X triplet amino acid motifs characteristi
c of the structure of human collagen. The structural gene (designated scl f
or streptococcal collagen-like) was present in all 50 GAS isolates tested,
which together express 21 different M protein types and represent the bread
th of genomic diversity in the species. DNA sequence analysis of the gene i
n these 50 isolates found that the number of contiguous Gly-X-X motifs rang
ed from 14 in serotype M6 isolates to 62 in a serotype M41 organism. M1 and
M18 organisms had the identical allele, which indicates very recent horizo
ntal g-ne transfer. The gene was transcribed abundantly in the logarithmic
but not stationary phase of growth, a result consistent with the occurrence
of a DNA sequence with substantial homology with a consensus Mga binding s
ite immediately upstream of the scl open reading frame. Two isogenic mutant
M1 strains created by nonpolar mutagenesis of the scl structural gene were
not attenuated for mouse virulence as assessed by intraperitoneal inoculat
ion. In contrast, the isogenic mutant derivative made from the M1 strain re
presentative of the subclone most frequently causing human infections was s
ignificantly less virulent when inoculated subcutaneously into mice. In add
ition, both isogenic mutant strains had significantly reduced adherence to
human A549 epithelial cells grown in culture. These studies identify a new
extracellular GAS virulence factor that is widely distributed in the specie
s and participates in adherence to host cells and soft tissue pathology.