Tissue-specific contributions of pneumococcal virulence factors to pathogenesis

J Infect Dis. 2004 Nov 1;190(9):1661-9. doi: 10.1086/424596. Epub 2004 Sep 21.


We assessed the ability of Streptococcus pneumoniae mutants deficient in either choline binding protein A (CbpA), pneumolysin (Pln), pyruvate oxidase (SpxB), autolysin (LytA), pneumococcal surface protein A, or neuraminidase A (NanA) to replicate in distinct anatomical sites and translocate from one site to the next. Intranasal, intratracheal, and intravenous models of disease were assessed in 4-week-old BALB/cJ mice by quantitation of bacterial titers in the relevant organs. Mice were also observed by use of real-time bioluminescent imaging (BLI). BLI allowed visualization of the bacteria in sites not tested by sampling. All mutants were created in D39 Xen7, a fully virulent derivative of capsular type 2 strain D39 that contains an optimized luxABCDE cassette. NanA, SpxB, and, to a lesser extent, CbpA contributed to prolonged nasopharyngeal colonization, whereas CbpA and NanA contributed to the transition to the lower respiratory tract. Once lung infection was established, Pln, SpxB, and LytA contributed to bacterial replication in the lungs and translocation to the bloodstream. In the bloodstream, only Pln and LytA were required for high-titer replication, whereas CbpA was required for invasion of the cerebrospinal fluid. We conclude that transitions between body sites require virulence determinants distinct from those involved in organ-specific replication.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacteremia
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cerebrospinal Fluid / microbiology
  • Disease Models, Animal
  • Female
  • Lung / microbiology
  • Meningitis, Pneumococcal / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • N-Acetylmuramoyl-L-alanine Amidase / genetics
  • N-Acetylmuramoyl-L-alanine Amidase / metabolism
  • Nasopharynx / microbiology
  • Neuraminidase / genetics
  • Neuraminidase / metabolism
  • Pneumococcal Infections / microbiology*
  • Pneumococcal Infections / pathology
  • Pneumonia, Pneumococcal / microbiology
  • Pyruvate Oxidase / genetics
  • Pyruvate Oxidase / metabolism
  • Streptococcus pneumoniae / genetics
  • Streptococcus pneumoniae / growth & development
  • Streptococcus pneumoniae / pathogenicity*
  • Streptolysins / genetics
  • Streptolysins / metabolism
  • Virulence Factors / genetics*
  • Virulence Factors / metabolism
  • Virulence Factors / physiology*


  • Bacterial Proteins
  • SpsA protein, Streptococcus pneumoniae
  • Streptolysins
  • Virulence Factors
  • plY protein, Streptococcus pneumoniae
  • pneumococcal surface protein A
  • Pyruvate Oxidase
  • Neuraminidase
  • N-Acetylmuramoyl-L-alanine Amidase