A pneumococcal pilus influences virulence and host inflammatory responses.
Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response.
Chiron Vaccines, 53100 Siena, Italy.
M A
MA
Barocchi
J
J
Ries
X
X
Zogaj
C
C
Hemsley
B
B
Albiger
A
A
Kanth
S
S
Dahlberg
J
J
Fernebro
M
M
Moschioni
V
V
Masignani
K
K
Hultenby
A R
AR
Taddei
K
K
Beiter
F
F
Wartha
A
A
von Euler
A
A
Covacci
D W
DW
Holden
S
S
Normark
R
R
Rappuoli
B
B
Henriques-Normark
D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D005798:Genes, Bacterial / Q000235:genetics / Q000502:physiology*; D044404:Genomic Islands / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D018410:Pneumonia, Bacterial / Q000382:microbiology*; D020545:Respiratory Mucosa / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000472:pathogenicity* / Q000648:ultrastructure; D015534:Trans-Activators / Q000235:genetics; D014774:Virulence
D001426:Bacterial Proteins; D015534:Trans-Activators; C470697:rlrA protein, Streptococcus pneumoniae