Streptococcus pyogenes causes an estimated 616 million pharyngitis cases per year
and a variety of invasive diseases such as necrotising fasciitis and toxic shock
syndrome. The human nasopharynx is the major reservoir for all S. pyogenes
infection, including severe invasive disease. A combination of biophotonic imaging
(BPI) and direct nasal sampling techniques were used to longitudinally measure the
in vivo carriage of S. pyogenes, looking at the effects of virulence factor expression
on carriage and transmission and to enable vaccine evaluation.
Direct nasal sampling demonstrated that the two component regulatory system,
CovR/S, is required for infection and transmission from the nasopharynx. The
fitness cost conferred by covR/S mutation in the nasopharynx may explain why S.
pyogenes with altered covR/S have not become prevalent in community infections
despite conferring a selective advantage in invasive infection.
Bioluminescent S. pyogenes strains expressing the luxABCDE operon demonstrated
a growth deficit independent of the target site for integration in vitro that manifested
as a fitness cost during infection in vivo. Notwithstanding this, bioluminescence
expression permitted longitudinal quantitation of S. pyogenes within the nasopharynx
using BPI. Intramuscular vaccination with heat killed streptococci or the
streptococcal chemokine protease SpyCEP conferred protection against pharyngeal
infection in this model.
These longitudinal techniques allow for S. pyogenes to be tracked in the
nasopharynx non-invasively, and allow for new insights into the pathogenesis of this
disease.