A pneumococcal pilus influences virulence and host inflammatory responses

TLDR

Pneumococcus is a leading global cause of disease, and its first step in invasive disease is attachment to upper respiratory tract epithelial cells. Pili-like appendages that enhance adhesion are encoded by the rlrA islet, which is present in some but not all clinical isolates. Pili expression driven by the rlrA islet boosts adherence to lung epithelial cells, gives a competitive edge in mouse models of colonization, pneumonia, and bacteremia, and provokes a heightened TNF‑mediated inflammatory response.

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.