The influence of in vitro fitness defects on pneumococcal ability to colonize and to cause invasive disease

• Main Authors: Morfeldt Eva, Blomberg Christel, Fernebro Jenny, Wolf-Watz Hans, Normark Staffan, Normark Birgitta
• Format: Article
• Language: English
• Published: BMC 2008-04-01
• Series: BMC Microbiology
• Online Access: http://www.biomedcentral.com/1471-2180/8/65

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus pneumoniae </it>is a genetically diverse major human pathogen, yet a common colonizer of the nasopharynx. Here we analyzed the influence of defects affecting <it>in vitro </it>growth rate, on the ability of <it>S. pneumoniae </it>to colonize and to cause invasive disease <it>in vivo</it>.</p> <p>Results</p> <p>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 (<it>ychF</it>, <it>hemK </it>and <it>yebC</it>) were, to different degrees, growth defective, and showed a reduced invasiveness in an intranasal murine challenge model that correlated to their <it>in vitro </it>growth rate, but remained capable of colonizing the upper airways. The growth defect, as well as virulence defect of the <it>hemK </it>insertion-deletion mutant, was mediated by polarity effects on the downstream <it>yrdC </it>gene, encoding a probable chaperone in ribosome assembly.</p> <p>Conclusion</p> <p>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.</p>