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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 inStreptococcus pneumoniae . Our results revealed thatS. pneumoniae possesses ade novo vitamin B6 biosynthesis pathway encoded by thepdxST genes. Purified PdxS functionally displayed as PLP synthase, whereas PdxT exhibited glutaminase activityin vitro . Deletion ofpdxS , but notpdxT , 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 ofpdxS 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 inS. 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.

journal of bacteriology

The Vitamin B <sub>6</sub> Biosynthesis Pathway in Streptococcus pneumoniae Is Controlled by Pyridoxal 5′-Phosphate and the Transcription Factor PdxR and Has an Impact on Ear Infection

The Vitamin B 6 Biosynthesis Pathway in Streptococcus pneumoniae Is Controlled by Pyridoxal 5′-Phosphate and the Transcription Factor PdxR and Has an Impact on Ear Infection

The Vitamin B ₆ Biosynthesis Pathway in Streptococcus pneumoniae Is Controlled by Pyridoxal 5′-Phosphate and the Transcription Factor PdxR and Has an Impact on Ear Infection