Abstract
Streptococcus pneumoniae represents a major Gram-positive human pathogen causing bacterial pneumonia, otitis media, meningitis, and other invasive diseases. Several pneumococcal isolates show increasing resistance rates against antibacterial agents. A variety of virulence factors promote pneumococcal pathogenicity with varying importance in different stages of host infection. Virulence related hair-like structures (“pili”) are complex, surface located protein arrays supporting proper host interaction. In the last two decades different types of pneumococcal pili have been identified: pilus-1 (P1) and pilus-2 (P2) are formed by the catalytic activity of sortases that covalently assemble secreted polypeptide pilin subunits in a defined order and finally anchor the resulting pilus in the peptidoglycan. Within the long pilus fiber the presence of intramolecular isopeptide bonds confer high stability to the sequentially arranged individual pilins. This mini review will focus on S. pneumoniae TIGR4 P1 molecular architecture, the subunits it builds and provides insights into P1 sortase-mediated assembly. The complex P1 architecture (anchor-/backbone-/tip-subunits) allows the specific interaction with various target structures facilitating different steps of colonization, invasion and spreading within the host. Optimized pilin subunit confirmation supports P1 function under physiological conditions. Finally, aspects of P1- host interplay are summarized, including recent insights into P1 mechanobiology, which have important implications for P1 mediated pathogenesis.
Highlights
Streptococcus pneumoniae A MAJOR HUMAN PATHOGEN EXPRESSING DIFFERENT TYPES OF PILIStreptococcus pneumoniae is a human commensal bacterium that can cause lethal diseases like pneumonia, septicemia, and meningitis
Broad-spectrum vaccination strategies and new antibacterials are of utmost importance to combat S. pneumoniae
The switch from a human commensal to an invasive pneumococcal pathogen and its disease causing capacity in various host niches is an area of intense study (Loughran et al, 2019)
Summary
Streptococcus pneumoniae A MAJOR HUMAN PATHOGEN EXPRESSING DIFFERENT TYPES OF PILI. Streptococcus pneumoniae (the pneumococcus) is a human commensal bacterium that can cause lethal diseases like pneumonia, septicemia, and meningitis. A multiplicity of differentially regulated cell surface located molecules mediate the complex interplay of S. pneumoniae and the human host This includes several types of high molecular weight protein assemblies, so-called pili, which promote pneumococcal virulence. P1 subunits show different numbers of stabilized individual domains [RrgA: 2 (Izoré et al, 2010); RrgB: 4 (El Mortaji et al, 2010, 2012a; Paterson and Baker, 2011), and RrgC: 2 (Shaik et al, 2014); Figure 1-A3] that might reflect individual pilin adaptation to generate an optimized P1 multimeric tool able to withstand mechanical perturbations induced during host interaction and supporting P1 assembly. Recent data imply that meningitis related neuronal death is mediated by an interaction of RrgA and pneumolysin with β-actin
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