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2017 ; 2
(2
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Opacification Domain of Serum Opacity Factor Inhibits Beta-Hemolysis and
Contributes to Virulence of Streptococcus pyogenes
#MMPMID28435893
Zhu L
; Olsen RJ
; Musser JM
mSphere
2017[Mar]; 2
(2
): ä PMID28435893
show ga
Serum opacity factor (SOF) is a cell surface virulence factor made by the human
pathogen Streptococcus pyogenes. We found that S. pyogenes strains with naturally
occurring truncation mutations in the sof gene have markedly enhanced
beta-hemolysis. Moreover, deletion of the sof gene in a SOF-positive parental
strain resulted in significantly increased beta-hemolysis. Together, these
observations suggest that SOF is an inhibitor of beta-hemolysis. SOF has two
major functional domains, including an opacification domain and a
fibronectin-binding domain. Using a SOF-positive serotype M89 S. pyogenes
parental strain and a panel of isogenic mutant derivative strains, we evaluated
the relative contribution of each SOF functional domain to beta-hemolysis
inhibition and bacterial virulence. We found that the opacification domain,
rather than the fibronectin-binding domain, is essential for SOF-mediated
beta-hemolysis inhibition. The opacification domain, but not the
fibronectin-binding domain of SOF, also contributed significantly to virulence in
mouse models of bacteremia and necrotizing myositis. Inasmuch as the
opacification domain of SOF is known to interact avidly with host high-density
lipoprotein (HDL), we speculate that SOF-HDL interaction is an important process
underlying SOF-mediated beta-hemolysis inhibition and SOF-mediated virulence.
IMPORTANCEStreptococcus pyogenes is a major human pathogen causing more than 700
million infections annually. As a successful pathogen, S. pyogenes produces many
virulence factors that facilitate colonization, proliferation, dissemination, and
tissue damage. Serum opacity factor (SOF), an extracellular protein, is one of
the virulence factors made by S. pyogenes. The underlying mechanism of how SOF
contributes to virulence is not fully understood. SOF has two major features: (i)
it opacifies host serum by interacting with high-density lipoprotein, and (ii) it
inhibits beta-hemolysis on blood agar. In this study, we demonstrate that the
domain of SOF essential for opacifying serum is also essential for SOF-mediated
beta-hemolysis inhibition and SOF-mediated virulence. Our results shed new light
on the molecular mechanisms of SOF-host interaction.