title: 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.
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: El Qaidi
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Jing-Ren
authors.initials: JR
authors.lastname: Zhang
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
authors.forename: Guangchun
authors.initials: G
authors.lastname: Bai
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000235:genetics / Q000378:metabolism*; D011732:Pyridoxal Phosphate / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025101:Vitamin B 6 / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors; D011732:Pyridoxal Phosphate; D025101:Vitamin B 6