No abstract

Streptococcus pneumoniae is among the most significant causes of bacterial disease in humans. Here we report the 2,038,615-bp genomic sequence of the gram-positive bacterium S. pneumoniae R6. Because the R6 strain is avirulent and, more importantly, because it is readily transformed with DNA from homologous species and many heterologous species, it is the principal platform for investigation of the biology of this important pathogen. It is also used as a primary vehicle for genomics-based development of antibiotics for gram-positive bacteria. In our analysis of the genome, we identified a large number of new uncharacterized genes predicted to encode proteins that either reside on the surface of the cell or are secreted. Among those proteins there may be new targets for vaccine and antibiotic development.

Biofilms are communal structures of microorganisms encased in an exopolymeric coat that form on both natural and abiotic surfaces and have been associated with a variety of persistent infections that respond poorly to conventional antibiotic chemotherapy. Biofilm infections of certain indwelling medical devices by common pathogens such as staphylococci are not only associated with increased morbidity and mortality but are also significant contributors to the emergence and dissemination of antibiotic resistance traits in the nosocomial setting. Current treatment paradigms for biofilm-associated infections of semipermanent indwelling devices typically involve surgical replacement of the device combined with long-term antibiotic therapy and incur high health care costs. This review summarizes the existing data relating to the nature, prevalence, and treatment of biofilm-associated infections and highlights experimental approaches and therapies that are being pursued toward more effective treatments.

SummaryWe report several new findings about the function of the essential VicRK two-component regulatory system (TCS) in the human pathogen Streptococcus pneumoniae . The vicR -encoded response regulator, vicK -encoded histidine kinase and the protein encoded by the downstream vicX gene are the homologues of the YycF, YycG and YycJ proteins, respectively, studied previously in Bacillus subtilis and Staphylococcus aureus. Using a regulatable promoter, we demonstrated that the VicK histidine kinase is conditionally required for growth of S. pneumoniae . Likewise, we found that the VicX protein is also conditionally required for growth and probably plays a role in the essential signal transduction pathway mediated by VicR and VicK. Recovery of limited substitutions in the conserved aspartate 52 residue (D52) of VicR was consistent with a requirement for phosphorylation of VicR for growth under some conditions. We applied microarrays to characterize the changes in transcription patterns in bacteria depleted for vicRKX operon expression. Our results suggest that the pcsB gene is a target of the VicRK TCS. We present evidence that downregulation of pcsB could account for many of the defects in cell growth, shape, size and morphology observed in bacteria depleted for vicRKX expression. Furthermore, constitutive expression of pcsB + + + + suppressed the essential requirement for the VicRK TCS and allowed the isolation of vicR null mutants.