The vitamin B6 biosynthesis pathway in streptococcus pneumoniae is controlled by pyridoxal 5'-phosphate and the transcription factor PdxR and has an impact on ear infection

Abstract

Vitamin B6 is an essential cofactor for a large number of enzymes in both prokaryotes and eukaryotes. In this study, we characterized the pyridoxal 5'-phosphate (PLP) biosynthesis pathway in Streptococcus pneumoniae. Our results revealed that S. pneumoniae possesses a de novo vitamin B6 biosynthesis pathway encoded by the pdxST genes. Purified PdxS functionally displayed as PLP synthase, whereas PdxT exhibited glutaminase activity in vitro. Deletion of pdxS, but not pdxT, resulted in a vitamin B6 auxotrophic mutant. The defective growth of the δpdxS mutant in a vitamin B6-depleted medium could be chemically restored in the presence of the B6 vitamers at optimal concentrations. By analyzing PdxS expression levels, we demonstrated that the expression of pdxS was repressed by PLP and activated by a transcription factor, PdxR. A pneumococcal δpdxR mutant also exhibited as a vitamin B6 auxotroph. In addition, we found that disruption of the vitamin B6 biosynthesis pathway in S. pneumoniae caused a significant attenuation in a chinchilla middle ear infection model and a minor attenuation in a mouse pneumonia model, indicating that the impact of vitamin B6 synthesis on virulence depends upon the bacterial infection niche. © 2013, American Society for Microbiology.