Group B Streptococcus (Streptococcus agalactiae or GBS) is the leading cause of gram positive neonatal meningitis and is an increasingly important cause of serious infection in elderly and chronically ill adults. Although GBS usually behaves as a harmless commensal colonizing the gastrointestinal and genital tracts of nearly a third of adult women, it has the capacity to produce life-threatening infection in susceptible hosts. The factors associated with the transition of GBS from harmless commensal to invasive pathogen are not known but are likely to involve a repertoire of bacterial mechanisms that respond to specific cues encountered in various host environments. It has been speculated that gram-positive and gram-negative bacteria utilize a density-dependent sensing mechanism (termed """"""""quorum sensing"""""""") through secretion of a LuxS dependent AI-2 signaling molecule that communicates with other organisms as well as regulates bacterial gene expression. We have identified and constructed a non-polar deletion mutant in a LuxS homolog in GBS. The luxS deletion mutant produces decreased bioluminescence in an AI-2 reporter strain of Vibrio harveyi compared to the wild type parent strain suggesting that GBS is capable of responding to the LuxS dependent AI-2 signaling molecule. The overall objectives of this proposal are to (1) determine the array of GBS genes regulated by the LuxS dependent AI-2 signaling molecule as well as determine the contribution of the AI-2 molecule to GBS virulence and (2) determine the molecular mechanism by which the LuxS dependent AI-2 signaling molecule regulates GBS gene expression. These objectives will be achieved by (A) comparing the transcriptisomes of wild type GBS and an isogenic luxS deletion mutant by microarray analysis followed by mouse lethality studies to assess the contribution of AI-2 to virulence and (B) constructing reporter fusions in genes regulated in response to the LuxS dependent AI-2 signaling molecule to determine if gene regulation is achieved by extracellular accumulation of a LuxS dependent AI-2 molecule.
| Puopolo, Karen M; Klinzing, David C; Lin, Michelle P et al. (2007) A composite transposon associated with erythromycin and clindamycin resistance in group B Streptococcus. J Med Microbiol 56:947-55 |
