Sortase-Mediated Pilus Fiber Biogenesis in Streptococcus pneumoniae

Clothilde Manzano, Carlos Contreras-Martel, Lamya El Mortaji, Thierry Izoré, Daphna Fenel, Thierry Vernet, Guy Schoehn, Anne Marie Di Guilmi, Andréa Dessen

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67 Citations (Scopus)

Abstract

Streptococcus pneumoniae is a piliated pathogen whose ability to circumvent vaccination and antibiotic treatment strategies is a cause of mortality worldwide. Pili play important roles in pneumococcal infection, but little is known about their biogenesis mechanism or the relationship between components of the pilus-forming machinery, which includes the fiber pilin (RrgB), two minor pilins (RrgA, RrgC), and three sortases (SrtC-1, SrtC-2, SrtC-3). Here we show that SrtC-1 is the main pilus-polymerizing transpeptidase, and electron microscopy analyses of RrgB fibers reconstituted in vitro reveal that they structurally mimic the pneumococcal pilus backbone. Crystal structures of both SrtC-1 and SrtC-3 reveal active sites whose access is controlled by flexible lids, unlike in non-pilus sortases, and suggest that substrate specificity is dictated by surface recognition coupled to lid opening. The distinct structural features of pilus-forming sortases suggest a common pilus biogenesis mechanism that could be exploited for the development of broad-spectrum antibacterials.

Original languageEnglish
Pages (from-to)1838-1848
Number of pages11
JournalStructure
Volume16
Issue number12
DOIs
Publication statusPublished - 12 Dec 2008
Externally publishedYes

Keywords

  • PROTEINS
  • SIGNALING

Cite this

Manzano, C., Contreras-Martel, C., El Mortaji, L., Izoré, T., Fenel, D., Vernet, T., Schoehn, G., Di Guilmi, A. M., & Dessen, A. (2008). Sortase-Mediated Pilus Fiber Biogenesis in Streptococcus pneumoniae. Structure, 16(12), 1838-1848. https://doi.org/10.1016/j.str.2008.10.007