A pneumococcal pilus influences virulence and host inflammatory responses

doi:10.1073/pnas.0511017103

A pneumococcal pilus influences virulence and host inflammatory responses

*Chiron Vaccines, 53100 Siena, Italy;
^‡Department of Bacteriology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden;
^§Microbiology and Tumorbiology Center, Karolinska Institutet, SE-17182 Stockholm, Sweden;
^¶Centre for Molecular Microbiology and Infection, Imperial College, London SW7 2AZ, United Kingdom;
^∥Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, 141 86 Huddinge, Sweden; and
**Centro Interdipartimentale di Microscopia Elettronica, University of Tuscia, 01100 Viterbo, Italy

Contributed by R. Rappuoli, December 21, 2005
↵ ^†M.A.B., J.R., and X.Z. contributed equally to this work.

Abstract

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.

Footnotes

^††To whom correspondence may be addressed at:
Chiron Corporation, Via Florentina 1l, Siena, Tuscany 53100, Italy.
E-mail: rino_rappuoli{at}chiron.com
^‡‡To whom correspondence may be addressed at:
Swedish Institute for Infectious Disease Control/MTC Karolinska Institutet, Nobels väg 18, SE-171 82 Solna, Sweden.
E-mail: birgitta.henriques{at}smi.ki.se
Author contributions: M.A.B., J.R., X.Z., C.H., B.A., D.W.H., S.N., and B.H.-N. designed research; M.A.B., J.R., X.Z., C.H., B.A., A.K., S.D., J.F., M.M., K.H., K.B., F.W., and A.v.E. performed research; M.A.B. contributed new reagents/analytical tools; M.A.B., J.R., X.Z., C.H., V.M., A.R.T., A.C., D.W.H., S.N., R.R., and B.H.-N. analyzed data; and M.A.B., J.R., and B.H.-N. wrote the paper.
Conflict of interest statement: M.A.B., M.M., V.M., and R.R. are employees of Chiron Corporation.
Abbreviations:

HMW,

high molecular weight;

cfu,

colony-forming units
Freely available online through the PNAS open access option.