Affiliation:
1. Department of Molecular Biology and Microbiology, Tufts University School of Medicine and Howard Hughes Medical Institute, Boston, Massachusetts, USA
Abstract
ABSTRACT
Streptococcus pneumoniae
is a commensal of the human nasopharynx but can cause invasive diseases, including otitis media, pneumonia, sepsis, and meningitis. The capsular polysaccharide (capsule) is a critical virulence factor required for both asymptomatic colonization and invasive disease, yet the expression level is different in each anatomical site. During colonization, reduced levels of capsule promote binding to the host epithelium and biofilm formation, while during systemic infection, increased capsule is required to evade opsonophagocytosis. How this regulation of capsule expression occurs is incompletely understood. To investigate the contribution of transcriptional regulation on capsule level in the serotype 4 strain TIGR4, we constructed two mutants harboring a constitutive promoter that was either comparably weaker (P
cat
) or stronger (P
tRNAGlu
) than the wild-type (WT) capsule promoter, P
cps
. Mild reductions in
cpsA
and
cpsE
transcript levels in the P
cat
promoter mutant resulted in a 2-fold reduction in total amounts of capsule and in avirulence in murine models of lung and blood infection. Additionally, the P
tRNAGlu
mutant revealed that, despite expressing enhanced levels of
cpsA
and
cpsE
and possessing levels of capsule comparable to those of WT TIGR4, it was still significantly attenuated in all tested
in vivo
niches. Further analysis using chimeric promoter mutants revealed that the WT −10 and −35 boxes are required for optimal nasopharyngeal colonization and virulence. These data support the hypothesis that dynamic transcriptional regulation of the capsule operon is required and that the core promoter region plays a central role in fine-tuning levels of capsule to promote colonization and invasive disease.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
67 articles.
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