Pyridoxine can inhibit salvage of other B6 vitamers in Salmonella enterica.

UNLABELLED: Pyridoxal 5'-phosphate (PLP) is a nutrient required by all life. As an essential cofactor, PLP powers enzymatic reactions in primary and secondary metabolism. Microbes can obtain PLP through either de novo PLP biosynthesis or the salvage of exogenous vitamin B6. Vitamin B6 exists in multiple forms (vitamers) in the natural environment, but the effect of mixed B6 vitamer supplementation on microbial physiology has not been explored. In this study, the ability of Salmonella enterica to obtain PLP during growth in media containing various ratios of B6 vitamers is examined. The data show that the B6 vitamer, pyridoxine (PN), can inhibit the salvage of B6 vitamers, pyridoxamine and pyridoxal, by S. enterica pdxH mutants. Genetic analyses were performed to determine the mechanism by which PN disrupts pyridoxamine and pyridoxal salvage. Mutants resistant to PN inhibition during the salvage of pyridoxamine were isolated and found to encode variants of B6 kinase (PdxK) with altered activity toward the B6 vitamer substrates. Suppressor analysis suggests that PN inhibition is, at least, partially due to competitive inhibition of the pyridoxamine kinase activity of PdxK by PN. Additionally, the data indicate that pyridoxine 5'-phosphate (PNP)-mediated toxicity also contributes to growth inhibition by PN.

IMPORTANCE: Without successful acquisition and utilization of vitamin B6, microbes cannot survive or perform their essential roles in human health and the natural environment. Vitamin B6 exists in multiple forms (vitamers) in the natural world, but the effect of B6 vitamer mixtures on microbial growth has not been analyzed. This work shows that the B6 vitamers are not necessarily interchangeable sources of PLP, and they may have distinct effects on microbial physiology.