title: The influence of in vitro fitness defects on pneumococcal ability to colonize and to cause invasive disease.
abstract: BACKGROUND
  Streptococcus pneumoniae is a genetically diverse major human pathogen, yet a common colonizer of the nasopharynx. Here we analyzed the influence of defects affecting in vitro growth rate, on the ability of S. pneumoniae to colonize and to cause invasive disease in vivo.
  
  
  RESULTS
  Of eleven different clinical isolates one serotype 14 carrier isolate showed a significantly longer generation time as compared to other isolates, and was severely attenuated in mice. To directly investigate the impact of growth rate on virulence, a panel of mutants in five non-essential housekeeping genes was constructed in the virulent TIGR4 background by insertion-deletion mutagenesis. Three of these mutants (ychF, hemK and yebC) were, to different degrees, growth defective, and showed a reduced invasiveness in an intranasal murine challenge model that correlated to their in vitro growth rate, but remained capable of colonizing the upper airways. The growth defect, as well as virulence defect of the hemK insertion-deletion mutant, was mediated by polarity effects on the downstream yrdC gene, encoding a probable chaperone in ribosome assembly.
  
  
  CONCLUSIONS
  We conclude that large fitness defects are needed to completely prevent pneumococci from causing invasive disease after intranasal challenge. However, even severe growth defects still allow pneumococci to persistently colonize the upper airways.
authors.affiliation: Swedish Institute for Infectious Disease Control, 171 82 Solna, Sweden. jenny.fernebro@smi.ki.se
authors.forename: Jenny
authors.initials: J
authors.lastname: Fernebro
authors.forename: Christel
authors.initials: C
authors.lastname: Blomberg
authors.forename: Eva
authors.initials: E
authors.lastname: Morfeldt
authors.forename: Hans
authors.initials: H
authors.lastname: Wolf-Watz
authors.forename: Staffan
authors.initials: S
authors.lastname: Normark
authors.forename: Birgitta Henriques
authors.initials: BH
authors.lastname: Normark
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D054643:INDEL Mutation; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009876:Operon; D011008:Pneumococcal Infections / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics* / Q000254:growth & development* / Q000472:pathogenicity; D013997:Time Factors; D014774:Virulence
chemical_list: D001426:Bacterial Proteins