In vivo proteomics identifies the competence regulon and AliB oligopeptide transporter as pathogenic factors in pneumococcal meningitis. Academic Article uri icon

Overview

abstract

  • Streptococcus pneumoniae (pneumococci) is a leading cause of severe bacterial meningitis in many countries worldwide. To characterize the repertoire of fitness and virulence factors predominantly expressed during meningitis we performed niche-specific analysis of the in vivo proteome in a mouse meningitis model, in which bacteria are directly inoculated into the cerebrospinal fluid (CSF) cisterna magna. We generated a comprehensive mass spectrometry (MS) spectra library enabling bacterial proteome analysis even in the presence of eukaryotic proteins. We recovered 200,000 pneumococci from CSF obtained from meningitis mice and by MS we identified 685 pneumococci proteins in samples from in vitro filter controls and 249 in CSF isolates. Strikingly, the regulatory two-component system ComDE and substrate-binding protein AliB of the oligopeptide transporter system were exclusively detected in pneumococci recovered from the CSF. In the mouse meningitis model, AliB-, ComDE-, or AliB-ComDE-deficiency resulted in attenuated meningeal inflammation and disease severity when compared to wild-type pneumococci indicating the crucial role of ComDE and AliB in pneumococcal meningitis. In conclusion, we show here mechanisms of pneumococcal adaptation to a defined host compartment by a proteome-based approach. Further, this study provides the basis of a promising strategy for the identification of protein antigens critical for invasive disease caused by pneumococci and other meningeal pathogens.

authors

  • Schmidt, Frank
  • Kakar, Niamatullah
  • Meyer, Tanja C
  • Depke, Maren
  • Masouris, Ilias
  • Burchhardt, Gerhard
  • Gómez-Mejia, Alejandro
  • Dhople, Vishnu
  • Håvarstein, Leiv S
  • Sun, Zhi
  • Moritz, Robert L
  • Völker, Uwe
  • Koedel, Uwe
  • Hammerschmidt, Sven

publication date

  • July 29, 2019

Research

keywords

  • Bacterial Proteins
  • Carrier Proteins
  • Lipoproteins
  • Meningitis, Pneumococcal
  • Streptococcus pneumoniae
  • Virulence Factors

Identity

PubMed Central ID

  • PMC6687184

Scopus Document Identifier

  • 85071348412

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.1007987

PubMed ID

  • 31356624

Additional Document Info

volume

  • 15

issue

  • 7